A standard approach to compiling clinical pharmacokinetic data

  • Lewis B. Sheiner
  • Leslie Z. Benet
  • Louis A. Pagliaro
Pharmacokinetic Data


A standard format for a Clinical Pharmacokinetic Summary is proposed. It consists of a heading, table, notes, and references for each drug reviewed. The table presents a unified and logical set of clinically useful population pharmacokinetic parameters. They concern four major areas: absorption, distribution, elimination, and the relationship of concentration to effect. Within each major group, parameters dealing with extents and rates of processes are given. Each such parameter is really two: a population mean value (for example, average volume of distribution) and the standard deviation of individual values about this mean. The first value allows individual predictions of dosage or drug level to be made; the second allows computation of the likely proximity of subsequently observed quantities to those predictions. The table presents single consensus values for each population parameter, rather than a list of values. A procedure for computing these consensus values, and for revising them in the light of new data, or reinterpreted old data, is given. Examples of Summaries are given. The method appears applicable to a variety of drugs. We suggest our approach as a standard one for preparing Clinical Pharmacokinetic Summaries, and urge our colleagues to consider it for that purpose.

Key words

Clinical Pharmacokinetic Summary population parameters data compilation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Alprenolol references

  1. 1.
    B. Ablad, K. O. Borg, G. Johnsson, C. G. Regardh, and L. Solvell. Combined pharmacokinetic and pharmacodynamic studies on alprenolol and 4-hydroxy-alprenolol in man.Life Sci. 14:693–704 (1974).PubMedGoogle Scholar
  2. 2.
    B. Ablad, M. Ervik, J. Hallgren, G. Johnsson, and L. Solvell. Pharmacological effects and serum levels of orally administered alprenolol in man.Eur. J. Clin. Pharmacol. 5:44–52 (1972).Google Scholar
  3. 3.
    G. Alvan, M. Lind, B. Mellstrom, and C. von Bahr. Importance of “first-pass elimination” for interindividual differences in steady-state concentrations of the adrenergic betareceptor antagonist alprenolol.J. Pharmacokin. Biopharm. 5:193–205 (1977).Google Scholar
  4. 4.
    G. Alvan, K. Piafsky, M. Lind, and C. von Bahr. Effect of pentobarbital on the disposition of alprenolol.Clin. Pharmacol. Ther. 22:316–321 (1977).PubMedGoogle Scholar
  5. 5.
    C. Appelgren, K. O. Borg, R. Elofsson, and K. A. Johansson. Binding of adrenergic beta-receptor antagonists to human serum albumin.Acta Pharmacol. Suec. 11:325–332 (1974).Google Scholar
  6. 6.
    N. O. Bodin. Identification of the major urinary metabolite of alprenolol in man, dog and rat.Life Sci. 14:685–692 (1974).PubMedGoogle Scholar
  7. 7.
    N. O. Bodin, K. O. Borg, R. Johansson, H. Obianwu. and R. Svensson. Absorption, distribution and excretion of alprenolol in man, dog and rat.Acta Pharmacol. Toxicol. 35:261–269 (1974).Google Scholar
  8. 8.
    O. Borga, K. M. Piafsky, and O. G. Nilsen. Plasma protein binding of basic drugs. I. Selective displacement from alpha 1-acid glycoprotein by tris (2-butoxyethyl) phosphate.Clin. Pharmacol. Ther. 22:539–44 (1977).PubMedGoogle Scholar
  9. 9.
    P. Collste, K. O. Borg, H. Astrom, and C. von Bahr. Contribution of 4-hydroxy-alprenolol to adrenergic beta-receptor blockade of alprenolol.Clin. Pharmacol. Ther. 25:416–422 (1979).PubMedGoogle Scholar
  10. 10.
    P. Collste, K. Haglund, M. Fisk-Holmberg, M. L. E. Orme, M. D. Rawlins, and J. Ostman. Pharmacokinetics and pharmacodynamics of alprenolol in the treatment of hypertension. II. Relationship to its effect on blood pressure and plasma renin activity.Eur. J. Clin. Pharmacol. 10:89–95 (1976).PubMedGoogle Scholar
  11. 11.
    P. Collste, K. Haglund, M. Frisk-Holmberg, and M. D. Rawlins. Pharmacokinetics and pharmacodynamics of alprenolol in the treatment of hypertension. I. Relationship between plasma concentration and adrenergic beta-receptor blockade.Eur. J. Clin. Pharmacol. 10:85–88 (1976).PubMedGoogle Scholar
  12. 12.
    M. Ervik. Gas Chromatographic determination of the secondary amine alprenolol, as its trifluoroacetyl derivative at nanogram levels in biological fluids.Acta Pharmacol. Suec. 6:393–400 (1969).Google Scholar
  13. 13.
    M. Frisk-Holmberg, L. Jorfeldt, and A. Juhlin-Dannfeldt. Influence of alprenolol on hemodynamic and metabolic responses to prolonged exercise in subjects with hypertension.Clin. Pharmacol. Ther. 21:675–684 (1977).PubMedGoogle Scholar
  14. 14.
    K. A. Johansson, C. Appelgren, K. O. Borg, and R. Elofsson. Binding of two adrenergic beta-receptor antagonists, alprenolol and H 93/26, to human serum proteins.Acta Pharmacol. Suec. 11:333–346 (1974).Google Scholar
  15. 15.
    R. Johansson, C. G. Regardh, and J. Sjogren. Absorption of alprenolol in man from tablets with different rates of release.Acta Pharmacol Suec. 8:59–70 (1971).Google Scholar
  16. 16.
    G. Johnsson, C. G. Regardh, and L. Solvell. Lack of biological interaction of alprenolol and salicylate in man.Eur. J. Clin. Pharmacol. 6:9–14 (1973).PubMedGoogle Scholar
  17. 17.
    G. Johnsson, J. Sjogren, and L. Solvell. Beta-blocking effect and serum levels of alprenolol in man after administration of ordinary and sustained release tablets.Eur. J. Clin. Pharmacol. 3:74–81 (1971).Google Scholar
  18. 18.
    K. M. Piafsky and O. Borga. Plasma protein binding of basic drugs. II. Importance of alpha 1-acid glycoprotein for interindividual variation.Clin. Pharmacol. Ther. 22:545–549 (1977).PubMedGoogle Scholar
  19. 19.
    M. D. Rawlins, P. Collste, M. Frisk-Holmberg, M. Lind, J. Ostman, and F. Sjoqvist. Steady-state plasma concentrations of alprenolol in man.Eur. J. Clin. Pharmacol. 7:353–356 (1974).PubMedGoogle Scholar

Clofibrate references

  1. 1a.
    A. M. Barrett and J. M. Thorp. Studies on the mode of action of clofibrate: effects on hormone-induced changes in plasma free fatty acids, cholesterol, phospholipids and total esterified fatty acids in rats and dogs.Br. J. Pharmacol. Chemother. 32:381–391 (1968).PubMedCentralPubMedGoogle Scholar
  2. 2a.
    H. Bruderlein, W. T. Robinson, M. Kraml, and D. Dvornik. A gas-liquid Chromatographic determination ofp-chlorophenoxyisobutyric acid and its comparison to an ultra violet method.Clin. Biochem. 8:261–272 (1975).PubMedGoogle Scholar
  3. 3a.
    L. F. Chasseaud, A. J. Cooper, and V. H. Saggers. Plasma concentrations and bioavailability of clofibrate after administration to human subjects.J. Clin. Pharmacol. 14:382–386 (1974).PubMedGoogle Scholar
  4. 4a.
    A. P. Goldberg, D. J. Sherrard, L. B. Haas, and J. D. Brunzell. Control of clofibrate toxicity in uremic hypertriglyceridemia.Clin. Pharmacol. Ther. 21:317–325 (1977).PubMedGoogle Scholar
  5. 5a.
    R. Gugler and J. Hartlapp. Clofibrate kinetics after single and multiple doses.Clin. Pharmacol. Ther. 24:432–438 (1978).PubMedGoogle Scholar
  6. 6a.
    R. Gugler, D+. W. Shoeman, D. H. Huffman, J. B. Cohlmia, and D. L. Azarnoff.J. Clin. Invest. 55:1182–1189 (1975).PubMedCentralPubMedGoogle Scholar
  7. 7a.
    C. Harvengt and J. P. Desager. Pharmacokinetic study and bioavailability of three marketed compounds releasingp-chlorophenoxyisobutyric acid (CPIB) in volunteers.Int. J. Clin. Pharmacol. 14:113–118 (1976).Google Scholar
  8. 8a.
    G. Houin and J. P. Tillement. Clofibrate and enzymatic induction in man.Int. J. Clin. Pharmacol. 16:150–154 (1978).Google Scholar
  9. 9a.
    G. Houin, J. J. Thebault, J. P. Tillement, and J. L. Beaumont. A GLC method for estimation of chlorophenoxyisobutyric acid in plasma. Pharmacokinetics of a single oral dose of clofibrate in man.Eur. J. Clin. Pharmacol. 8:433–437 (1975).PubMedGoogle Scholar
  10. 10a.
    P. T. Mannisto, J. Tuomisto, A. Jounela, and O. Penttila. Pharmacokinetics of clofibrate and chlorophenoxyisobutyric acid. I. Cross-over studies on human volunteers.Acta Pharmacol. Toxicol. 36:353–365 (1974).Google Scholar
  11. 11a.
    B. Pichardo, L. Boulet, and J. Davignon. Pharmacokinetics of clofibrate in familial hypercholesterolemia.Artherosclerosis 26:573–584 (1977).Google Scholar
  12. 12a.
    A. Sedaghat and E. H. Ahrens. Lack of effect of cholestyramine on the pharmacokinetics of clofibrate in man.Eur. J. Clin. Invest. 5:177–185 (1975).PubMedGoogle Scholar
  13. 13a.
    A. Sedaghat, H. Nakamura, and E. H. Ahrens. Determination of clofibrate in biological fluids by thin-layer and gas-liquid chromatography.J. Lipid Res. 15:352–355 (1974).PubMedGoogle Scholar
  14. 14a.
    T. Taylor and L. F. Chasseaud. Plasma concentrations and bioavailability of clofibric acid from its calcium salt in humans.J. Pharm. Sci. 66:1638–1639 (1977).PubMedGoogle Scholar
  15. 15a.
    J. M. Thorp. Experimental evaluation of an orally active combination of androsterone with ethyl chlorophenoxyisobutyrate.Lancet I:1323–1326 (1962).Google Scholar

Digitoxin references

  1. 1b.
    B. Beermann, K. Hellstrom, and A. Rosen. Fare of orally administered 3H-digitoxin in man with special reference to the absorption.Circulation 43:852–861 (1971).PubMedGoogle Scholar
  2. 2b.
    G. A. Beller, T. W. Smith, W. H. Abelmann, E. Haber, and W. B. Hood. Digitalis intoxication.N. Engl. J. Med. 284:989–997 (1971).PubMedGoogle Scholar
  3. 3b.
    F. M. Belpaire, M. G. Bogaert, and M. M. Mussche. Influence of acute renal failure on the protein binding of drugs in animals and in man.Eur. J. Clin. Pharmacol. 11:27–32 (1977).PubMedGoogle Scholar
  4. 4b.
    G. G. Belz, R. Erbel, K. Schumann, and H. J. Gilfrich. Dose-response relationships and plasma concentrations of digitalis glycosides in man.Eur. J. Clin. Pharmacol. 13:103–111 (1978).PubMedGoogle Scholar
  5. 5b.
    J. D. Bentley, G. H. Burnett, R. L. Conklin, and R. H. Wasserburger. Clinical application of serum digitoxin levels.Circulation 41:67–75 (1970).PubMedGoogle Scholar
  6. 6b.
    G. Bodem and E. V. Unruh. Enhanced transformation of digitoxin to dihydrodigitoxin in humans with renal failure.J. Clin. Pharmacol. 19:195–199 (1979).PubMedGoogle Scholar
  7. 7b.
    G. Brooker and R. W. Jelliffe. Serum cardiac glycoside assay based upon displacement of 3H-ouabain from Na-K ATPase.Circulation 45:20–36 (1972).PubMedGoogle Scholar
  8. 8b.
    J. H. Caldwell, C. A. Bush, and N. J. Greenberger. Interruption of the enterohepatic circulation of digitoxin by cholestyramine.J. Clin. Invest. 50:941–950 (1971).Google Scholar
  9. 9b.
    W. A. Craig, M. A. Evenson, K. P. Sarver, and J. P. Wagnild. Correction of protein binding defect in uremic sera by charcoal treatment.J. Lab. Clin. Med. 87:637–647 (1976).PubMedGoogle Scholar
  10. 10b.
    V. G. Faust-Tinnefeldt and H. J. Gilfrich. Digitoxin-kinetik unter antirheumatischer therapie mit azapropazon.Drug Res. 27:2009–2011 (1977).Google Scholar
  11. 11b.
    F. O. Findelstein, J. A. Goffinet, E. D. Hendler, and J. Lindenbaum. Pharmacokinetics of digoxin and digitoxin in patients undergoing hemodialysis.Am. J. Med. 58:525–531 (1975).Google Scholar
  12. 12b.
    W. Forester, R. P. Lewis, A. M. Weissler, and T. A. Wilke. The onset and magnitude of the contractile response to commonly used digitalis glycosides in normal subjects,Circulation 49:517–521 (1974).PubMedGoogle Scholar
  13. 13b.
    A. C. V. Giardina, K. H. Ehlers, J. B. Morrison, and M. E. Engle. Serum digitoxin concentrations in infants and childrenCirculation 51:713–717 (1975).PubMedGoogle Scholar
  14. 14b.
    K. Gjerdrum. Determination of digitalis in blood.Acta Med. Scand. 187:371–379 (1970).PubMedGoogle Scholar
  15. 15b.
    K. Gjerdrum. Serum concentration during digitalization, maintenance therapy and withdrawal.Acta Med. Scand. 191:25–34 (1972).PubMedGoogle Scholar
  16. 16b.
    R. W. Jelliffe. A mathematical analysis of digitalis kinetics in patients with normal and reduced renal function.Math. Biosci. 1:305–325 (1967).Google Scholar
  17. 17b.
    R. W. Jelliffe, J. Buell, R. Kalaba, R. Sridhar, and R. Rockwell. A mathematical study of the metabolic conversion of digitoxin to digoxin in man.Math. Biosci. 6:387–403 (1970).Google Scholar
  18. 18b.
    A. Kober, I. Sjoholm, O. Borga, and I. Odar-Cederlof. Protein binding of diazepam and digitoxin in uremic nd normal serum.Biochem. Pharmacol. 28:1037–1042 (1979).PubMedGoogle Scholar
  19. 19b.
    P. Kramer, E. Kothe, J. Sauld, and F. Scheler. Uraemic and normal plasma protein binding of various cardiac glycosides under “in vivo” conditions.Eur. J. Clin. Invest. 4:53–58 (1974).PubMedGoogle Scholar
  20. 20b.
    D. S. Lukas. Some aspects of the distribution and disposition of digitoxin in man.Ann. N. Y. Acad. Sci. 179:338–361 (1971).PubMedGoogle Scholar
  21. 21b.
    D. S. Lukas and A. G. DeMartin. Binding of digitoxin and some related cardenolides to human plasma proteins.J. Clin. Invest. 48:1041–1053 (1969).PubMedCentralPubMedGoogle Scholar
  22. 22b.
    D. A. Lukas and R. E. Peterson. Double isotope dilution derivative assay of digitoxin in plasma, urine and stool of patients maintained on the drug.J. Clin. Invest. 45:782–795 (1966).PubMedCentralPubMedGoogle Scholar
  23. 23b.
    J. Morrison and T. Killip. Serum digitalis and arrhythmia in patients undergoing cardiopulmonary bypass.Ciculation 47:341 (1973).Google Scholar
  24. 24b.
    G. C. Oliver, B. M. Barker, D. L. Prasfield, and C. W. Parker. The measurement of digitoxin in human serum by radioimmunoassay.J. Clin. Invest. 47:1035–1042 (1968).PubMedCentralPubMedGoogle Scholar
  25. 25b.
    D. Perrier, M. Mayersohn, and F. I. Marcus. Clinical pharmacokinetics of digitoxin.Clin. Pharmacokin. 2:292–311 (1977).Google Scholar
  26. 26b.
    U. Peters, T.-U. Hausamen, and F. Grosse-Brockhoff. The effects of antituberculosis drugs on the pharmacokinetics of digitoxin.Deutsch med. Wschr. 99:2381–2386 (1974).PubMedGoogle Scholar
  27. 27b.
    K. Rasmussen, J. Jervell, L. Storstein, and K. Gjerdrum. Digitoxin kinetics in patients with impaired renal function.Eur. J. Clin. Pharmacol 13:6–14 (1971).Google Scholar
  28. 28b.
    L. W. Ritzmann, C. C. Bangs, D. Coiner, J. M. Custis, and J. R. Walsh. Serum glycoside levels by rubidium assay.Arch. Intern. Med. 132:823–830 (1973).PubMedGoogle Scholar
  29. 29b.
    W. Shapiro, K. Narahara, and K. Taubert. Relationship of plasma digitoxin and digoxin to cardiac response following intravenous digitalization in man.Circulation 42:1065–1072 (1970).PubMedGoogle Scholar
  30. 30b.
    D. W. Shoeman, and D. L. Azarnoff. The alteration of plasma proteins in uremia as reflected in their ability to bind digitoxin and diphenylhydantoin.Pharmacol. 7:169–177 (1972).Google Scholar
  31. 31b.
    T. W. Smith. Radioimmunoassay for serum digitoxin concentration: methodology and clinical experience.J. Pharmacol. Exp. Ther. 175:352–360 (1970).PubMedGoogle Scholar
  32. 32b.
    H. M. Solomon, S. Reich, N. Spirt, and W. B. Abrams. Interactions between digitoxin and other drugs in vitro and in vivo.Ann. N. Y. Acad. Sci. 179:362–369 (1971).PubMedGoogle Scholar
  33. 33b.
    R. G. Stoll, M. S. Christensen, E. Sakmar, D. Blair, and J. G. Wagner. Determination of bioavailability of digitoxin using the radioimunoassay procedure.J. Pharm. Sci. 62:1615–1620 (1973).PubMedGoogle Scholar
  34. 34b.
    L. Storstein. Studies on digitalis I. Renal excretion of digitoxin and its cardioactive metabolites.Clin. Pharmacol. Ther. 16:14–24 (1974).PubMedGoogle Scholar
  35. 35b.
    L. Storstein. Studies on digitalis. II. The influence of impaired renal function on the renal excretion of digitoxin and its cardioactive metabolites.Clin. Pharmacol. Ther. 16:25–34 (1974).PubMedGoogle Scholar
  36. 36b.
    L. Storstein. Studies on digitalis III. Biliary excretion and enterohepatic circulation of digitoxin and its cardioactive metabolites.Clin. Pharmacol. Ther. 17:313–320 (1975).PubMedGoogle Scholar
  37. 37b.
    L. Storstein. Studies on digitalis. V. The influence of impaired renal function, hemodialysis and drug interaction on serum protein binding of digitoxin and digoxin.Clin. Pharmacol. Ther. 20:6–14 (1976).PubMedGoogle Scholar
  38. 38b.
    L. Storstein and H. Janssen. Studies on digitalis. VI. The effect of hepairin on serum protein binding of digitoxin and digoxin.Clin. Pharmacol. Ther. 20:15–23 (1976).PubMedGoogle Scholar
  39. 39b.
    L. Storstein. Studies on digitalis. VII. influence of nephrotic syndrome on protein binding, pharmacokinetics, and renal excretion of digitoxin and cardioactive metabolites,Clin. Pharmacol. Ther. 20:158–166 (1976).PubMedGoogle Scholar
  40. 40b.
    L. Storstein. Studies on digitalis. X. Digitoxin metabolites in human myocardium and relationship between myocardial and serum concentrations of digitoxin in patients on maintenance treatment.Clin. Pharmacol. Ther. 21:395–408 (1977).PubMedGoogle Scholar
  41. 41b.
    O. Storstein, V. Hansteen, L. Hatle, L. Hillestad, and L. Storstein. Studies on digitalis. XIII. A prospective study of 649 patients on maintenance treatment with digitoxin.Am. Heart J. 93:434–443 (1977).PubMedGoogle Scholar
  42. 42b.
    R. J. van Bever, A. M. J. Duchateau, B. F. Pluym, and F. W. H. Merkus, The effect of colestipol on digitoxin plasma levels.Arzneim-forsch. 26:1891–1893 (1976).Google Scholar
  43. 43b.
    H. F. Vohringer and N. Rietbrock. Metabolism and excretion of digitoxin in man.Clin. Pharmacol. Ther. 16:796–806 (1974).PubMedGoogle Scholar
  44. 44b.
    H. F. Vohringer, N. Rietbrock, P. Spurny, J. Kuhlmann, H. Hampl, and R. Baethke. Disposition of digitoxin in renal failure.Clin. Pharmacol. Ther. 19:387–395 (1976).PubMedGoogle Scholar
  45. 45b.
    W. S. Wilson, J. H. Tolbert, and W. DiGuilio. Plasma digitoxin levels and serial left ventricular ejection times after a digitalizing dose of digitoxin.Am. J. Cardiol 26:162–164 (1970).PubMedGoogle Scholar
  46. 46b.
    K. E. Wirth, J. C. Frolich, J. W. Hollifield, F. C. Falkner, B. S. Sweetman, and J. A. Oates. Metaboism of digitoxin in man and its modification by spironolactone.Eur. J. Clin. Pharmacol. 9:345–354 (1976).Google Scholar

Digitoxin: supplementary references

  1. 47b.
    R. W. Jelliffe, J. Buell, and R. Kalaba. Reduction of digitalis toxicity by computer-assisted glycoside dosage regimens.Ann. Int. Med. 77:891–906 (1972).PubMedGoogle Scholar
  2. 487b.
    R. W. Jelliffe, J. Buell, R. Kalaba, R. Sridhar, R. Rockwell, and J. G. Wagner. An improved method of digitoxin therapy.Ann. Intern. Med. 72:453–464 (1970).PubMedGoogle Scholar
  3. 49b.
    G. T. Okita. Metabolism of radioactive cardiac glycosides.Pharmacol. 6:45 (1964).Google Scholar
  4. 50b.
    W. Shapiro, K. Taubert, and K. Narahara. Nonradioactive serum digoxin and digitoxin levels.Arch. Intern. Med. 130:310 (1972).Google Scholar
  5. 51b.
    L. Storstein. Studies on digitalis XI. Digitoxin metabolism on a maintenance regimen and after a single dose.Clin. Pharmacol. Ther. 21:125–140 (1977).PubMedGoogle Scholar
  6. 52b.
    L. Storstein. Studies on digitalis XII. Kinetic pattern of digitoxin metabolism in patients with biliary fistulas.Clin. Pharmacol. Ther. 21:659–674 (1977).PubMedGoogle Scholar
  7. 53b.
    L. Storstein and J. Amlie. Studies on digitalis IX. Some kinetic aspects of digitoxin metabolism.Clin. Pharmacol. Ther. 21:255–266 (1977).PubMedGoogle Scholar

Digoxin references

  1. 1c.
    K. S. Albert, J. W. Ayres, A. R. DiSanto, D. J. Weidler, E. Sakmar, M. R. Hallmark, R. G. Stoll, K.A. DeSante, and J. G. Wagner. Influence of kaolin-pectin suspension on digoxin bioavailability.J. Pharm. Sci. 67:1582–1585 (1978).PubMedGoogle Scholar
  2. 2c.
    H. Allonen, E. Ilsalo, L. Kangas, R. Lammintausta, and M. Salonen. Estimation of pharmacokinetic parameters of digoxin from serum, saliva and urine.Int. J. Clin. Pharmacol. 16:420–423 (1978).Google Scholar
  3. 3c.
    H. Allonen, K. Kanto, and E. Iisalo. The foeto-maternal distribution of digoxin in early human pregnancy.Acta Pharmacol. Toxicol. 39:477–480 (1976).Google Scholar
  4. 4c.
    K. E. Andersson, A. Bertler, and G. Wettrell. Post-mortem distribution and tissue concentrations of digoxin in infants and adults.Acta Paeditr. Scand. 64:497–504 (1975).Google Scholar
  5. 5c.
    J. K. Aronson. Monitoring digoxin therapy: III. How useful are the nomograms?Br. J. Clin. Pharmacol. 5:55–64 (1978).PubMedCentralPubMedGoogle Scholar
  6. 6c.
    F. M. Belpaire, M. G. Bogaert, and M. E. DeBroe. Radioimmunoassay of digoxin in renal failure: a comparison of different commercial kits.Clin. Chim. Acta 62:255–261 (1975).PubMedGoogle Scholar
  7. 7c.
    A. Bertler, M. Monti, P. Ohlin, and A. Redfors. Cardiac arrhythmias, electrolytes, and digoxin concentration in plasma and urine in patients treated with digoxin.Acta Med. Scand. 197:391–401 (1975).PubMedGoogle Scholar
  8. 8c.
    A. Bertler and A. Redfors. Plasma levels of digoxin in relation to toxicity.Acta Pharmacol. Toxicol. (Suppl).3:281–287 (1971).Google Scholar
  9. 9c.
    T. Beveridge, E. Nuesch, and E. E. Ohnhaus. Absolute bioavailability of digoxin tablets.Arzneimittel-forsch. 28:701–703 (1978).Google Scholar
  10. 10c.
    T. L. Biddle, M. Weintraub, and L. Lasagna. Relationship of serum and myocardial digoxin concentration to electrocardiographic estimation of digoxin intoxication.J. Clin. Pharmacol. 18:10–15 (1978).PubMedGoogle Scholar
  11. 11c.
    G. A. Beller, T. W. Smith, W. H. Abelmann, E. Haber, and W. B. Hood. Digitalis intoxication, a prospective clinical study with serum level correlations.M. Engl. J. Med. 284:979–997 (1971).Google Scholar
  12. 12c.
    P. F. Binnion. Absorption of different commercial preparations of digoxin in the normal human subject, and the influence of antacid, antidiarrhoeal and ion-exchange agents.Symposium on Digitalis, 1973, pp. 216–224.Google Scholar
  13. 13c.
    P. F. Binnion. A comparison of the bioavailability of digoxin in capsule, tablet and solution taken orally with intravenous digoxin.J. Clin. Pharmacol. 16:461–467 (1976).PubMedGoogle Scholar
  14. 14c.
    J. Bonelli, H. Haydl, K. Hruby, and G. Kaik. The pharmacokinetics of digoxin in patients with manifest hyperthyroidism and after normalization of thyroid function.Int. J. Clin. Pharmacol. 16:302–306 (1978).Google Scholar
  15. 15c.
    D. C. Brater and H. F. Morrelli. Digoxin toxicity in patients with normokalemic potassium depletion.Clin. Pharmacol. Ther. 22:21–33 (1977).PubMedGoogle Scholar
  16. 16c.
    D. D. Brown, J. C. Dormois, and G. N. Abraham. Effect of furosemide on the renal excretion of digoxin.Clin. Pharmacol. Ther. 20:395–400 (1976).PubMedGoogle Scholar
  17. 17c.
    D. D. Brown and R. P. Juhl. Decreased bioavailability of digoxin due to antacids and kaolin pectin.N. Engl. J. Med. 295:1034–1037 (1976).PubMedGoogle Scholar
  18. 18c.
    D. D. Brown, R. P. Juhl, and S. L. Warner. Decreased bioavailability of digoxin due to hypocholesterolemic interventions.Circulation 58:164–172 (1978).PubMedGoogle Scholar
  19. 19c.
    N. Buchanan, L. A. Van Der Walt, and B. Strickwood. Pharmacology of malnutrition III: binding of digoxin to normal and kwashiorkor serum.J. Pharm. Sci. 65:914–916 (1976).PubMedGoogle Scholar
  20. 20c.
    G. H. Burnett, R. L. Conklin, G. W. Wasson, and A. A. MacKinney. Variability of standard curves in radioimmunoassay of plasma digoxin.Clin. Chem. 19:725–726 (1973).PubMedGoogle Scholar
  21. 21c.
    J. H. Caldwell and C. T. Cline. Biliary excretion of digoxin in man.Clin. Pharmacol. Ther. 19:410–415 (1976).PubMedGoogle Scholar
  22. 22c.
    N. H. Carliner, C. A. Gilbert, A. W. Pruitt, and L. I. Goldberg. Effects of maintenance digoxin therapy on systolic time intervals and serum digoxin concentrations.Circulation 50:94–98 (1974).PubMedGoogle Scholar
  23. 23c.
    P. R. Carroll, A. Gelbart, M. F. O'Rourke, and J. Shortus. Digoxin concentrations in the serum and myocardium of digitalized patients,Aust. N.Z. Med. 3:400–403 (1973).Google Scholar
  24. 24c.
    N. J. Christiansen, K. Kolendorf, K. Siersbaek-Nielsen, and J. Molholm Hansen. Serum digoxin values following a dosage regimen based on body weight, sex, age and rena! function.Acta Med. Scand. 194:257–259 (1973).PubMedGoogle Scholar
  25. 25c.
    D. R. Clark and S. M. Kaiman. Dihydrodigoxin: a common metabolite of digoxin in man,Drug Metab. Dispos. 2:148–150 (1974).PubMedGoogle Scholar
  26. 26c.
    K. Cohn, A. Selzer, E. S. Kersh, L. S. Karpman, and N. Goldschlager. Variability of hemodynamic responses to acute digitalization in chronic cardiac failure due to cardiomyopathy and coronary artery disease,Am. J. Cardiol. 35:461–468 (1975).PubMedGoogle Scholar
  27. 27c.
    M. S. Croxson and H. K. Ibbertson. Serum digoxin in patients with thyroid disease.Br. Med. J. 3:566–568 (1975).PubMedCentralPubMedGoogle Scholar
  28. 28c.
    B. Cusack, J. Horgan, J. G. Kelly, J. Lavan, J. Noel, and K. O'Malley. Pharmacokinetics of digoxin in the elderly.Proceedings of the British Pharmacological Society, Clinical Pharmacology Section 13–15, September (1978), 439P–440P.Google Scholar
  29. 29c.
    B. Cusack, J. Kelly, K. O'Malley, J. Noel, J. Lavan, and J. Horgan. Digoxin in the elderly: Pharmacokinetic consequences of old age.Clin. Pharmacol. Ther. 25:772–776 (1979).PubMedGoogle Scholar
  30. 30c.
    W. Doering. Quinidine-digoxin interaction. Pharmacokinetics, underlying mechanism and clinical implications.N. Engl. J. Med. 301:400–404 (1979).PubMedGoogle Scholar
  31. 31c.
    J. E. Doherty. Pharmacokinetics and their clinical implications.Ann. Intern. Med. 79:229–238 (1973).PubMedGoogle Scholar
  32. 32c.
    J. E. Doherty, W. J. Flanigan, and G. V. Dalrymple. XVII. Excretion and turnover times in normal donors before and after nephrectomy and in the paired recipient of the kidney after transplantation.Am. J. Cardiol. 29:470–474 (1972).PubMedGoogle Scholar
  33. 33c.
    J. E. Doherty, J. Flanigan, M. L. Murphy, R. T. Bulloch, G. L. Dalrymple, O. W. Beard, and W. H. Perkins. XIV. Enterohepatic circulation, absorption and excretion studies in human volunteers.Circulation 42:867–873 (1970).PubMedGoogle Scholar
  34. 34c.
    J. E. Doherty, W. J. Flanigan, W. H. Perkins, and G. L. Ackerman. Studies with tritiated digoxin in anephric human subjects,Circulation 35:298–303 (1967).PubMedGoogle Scholar
  35. 35c.
    J. E. Doherty and W. Hall. Tritiated digoxin.Am. J. Cardiol. 28:326–330 (1971).PubMedGoogle Scholar
  36. 36c.
    J. E. Doherty and W. H. Perkins. Studies with tritiated digoxin in human subjects after intravenous administration,Am. Heart J. 63:528–536 (1962).PubMedGoogle Scholar
  37. 37c.
    J. E. Doherty and W. H. Perkins. Studies following intramuscular tritiated digoxin in human subjects.Am. J. Cardiol. 15:170–174 (1965).PubMedGoogle Scholar
  38. 38c.
    J. E. Doherty and W. H. Perkins. Digoxin metabolism in hypo- and hyperthyroidism.Ann. Intern. Med. 64:489–507 (1966).PubMedGoogle Scholar
  39. 39c.
    J. E. Doherty, W. H. Perkins, and G. K. Mitchell. Tritiated digoxin studies in human subjects.Arch. Intern. Med. 108:531–539 (1961).PubMedGoogle Scholar
  40. 40c.
    W. T. Dungan, J. E. Doherty, C. Harvey, F. Char, and G. V. Dalrymple. Tritiated digoxin XVIII. Studies in infants and children.Circulation 46:983–988 (1972).PubMedGoogle Scholar
  41. 41c.
    D. C. Evered. The binding of digoxin by the serum proteins.Eur. J. Pharmacol. 18:236–244 (1972).PubMedGoogle Scholar
  42. 42c.
    D. C. Evered and C. Chapman. Plasma digoxin concentrations and digoxin toxicity in hospital patients.Br. Heart J. 33:540–545 (1971).PubMedCentralPubMedGoogle Scholar
  43. 43c.
    G. A. Ewy, B. M. Groves, M. F. Ball, L. Nimmo, B. Jackson, and F. Marcus. Digoxin metabolism in obesity.Circulation 44:810–814 (1971).PubMedGoogle Scholar
  44. 44c.
    G. A. Ewy, G. G. Kapadia, L. Yao, M. Lullin, and F. I. Marcus. Digoxin metabolism in the elderly,Circulation 39:449–453 (1969).PubMedGoogle Scholar
  45. 45c.
    L. Fleckenstein, L. Z. Benet, and P. D. Thomson. Pharmacokinetic evaluation of a patient with unusually high digoxin (D) requirements.Clin. Pharmacol. Ther. 21:102 (1977).Google Scholar
  46. 46c.
    L. Fleckenstein, B. Kroening, and M. Weintraub. Assessment of the biologic availability of digoxin in man.Clin. Pharmacol. Ther. 16:435–443 (1974).PubMedGoogle Scholar
  47. 47c.
    A. M. Fogelman, J. LaMont, S. Finkelstein, E. Rado, and M. Pearce. Fallibility of plasma-digoxin in differentiating toxic from non-toxic patients.Lancet II:727–729 (1971).Google Scholar
  48. 48c.
    H. M. Gault, J. R. Jeffrey, E. Chirito, and L. L. Ward. Studies of digoxin dosage, kinetics and serum concentrations in renal failure and review of the literature.Nephron 17:161–187 (1976).PubMedGoogle Scholar
  49. 49c.
    M. H. Gault, D. Sugden, C. Maloney, M. Ahmed, and M. Tweeddale. Biotransformation and elimination of digoxin with normal and minimal renal function.Clin. Pharmacol. Ther. 25:499–513 (1979).PubMedGoogle Scholar
  50. 50c.
    J. M. Gayes, D. J. Greenblatt, B. L. Lloyd, J. S. Harmatz, and T. W. Smith. Cerebrospinal fluid digoxin concentrations in humans.J. Clin. Pharmacol. 18:16–20 (1978).PubMedGoogle Scholar
  51. 51c.
    H. J. Gilfrich. Untersuchungen zur pharmakokinetik von digoxin bei hyperthyreoten patienten.Verh. Deutsch. Ges. 82(pt. 2):1726–1728 (1976).Google Scholar
  52. 52c.
    R. Gorodischer, W. J. Jusko, and S. J. Yaffe. Tissue and erythrocyte distribution of digoxin in infants.Clin. Pharmacol. Ther. 19:256–263 (1976).PubMedGoogle Scholar
  53. 53c.
    R. Gorodischer, W. J. Jusko, and S. J. Yaffe. Renal clearance of digoxin in young infants.Res. Comm. Chem. Pathol. Pharmacol. 16:363–373 (1977).Google Scholar
  54. 54c.
    D. J. Greenblatt, D. W. Duhme, J. Koch-Weser, and T. W. Smith. Evaluation of digoxin bioavailability in single-dose studies.N. Engt J. Med. 289:651–654 (1973).Google Scholar
  55. 55c.
    D. J. Greenblatt, D. W. Duhme, J. Koch-Weser, and T. W. Smith. Bioavailability of digoxin tablets and elixir in the fasting and postprandial states.Clin. Pharmacol. Ther. 16:444–448 (1974).PubMedGoogle Scholar
  56. 56c.
    D. J. Greenblatt, D. W. Duhme, J. Koch-Weser, and T. W. Smith. Intravenous digoxin as a bioavailability standard: slow infusion and rapid injection.Clin. Pharmacol. Ther. 15:510–513 (1974).PubMedGoogle Scholar
  57. 57c.
    D. J. Greenblatt, T. W. Smith, and J. Koch-Weser. Bioavailability of drugs: the digoxin dilemma.Clin. Pharmacokin. 1:36–51 (1976).Google Scholar
  58. 58c.
    H. Greenwood, W. Snedden, and R. P. Hayward. The measurement of urinary digoxin and dihydrodigoxin by radioimmunoassay and by mass spectroscopy.Clin. Chem. Acta 62:213–224 (1975).Google Scholar
  59. 59c.
    S. Gutcho, H. McCarter, and R. Rapun. Radioimmunoassay of digoxin: an intercomparison of results with three methods.Clin. Chem. 19:1058–1059 (1973).PubMedGoogle Scholar
  60. 60c.
    R. Haasis, D. Larbig, R. Stunkat, H. Bader, and H. Sebolt. Determination of glycoside concentrations in human tissue by means of radioimmunoassay.Klin. Wschr. 55:23–30 (1977).PubMedGoogle Scholar
  61. 61c.
    W. D. Hager, P. Fenster, M. Mayersohn, D. Perrier, P. Graves, F. I. Marcus, and S. Goldman. Digoxin-quinidine interaction: pharmacokinetic evaluation.N. Engl. J. Med. 300:1238–1241 (1979).PubMedGoogle Scholar
  62. 62c.
    H. Halkin, M. Radomsky, L. Blieden, M. Frand, P. Millman, and H. Boichis. Steady-state serum digoxin concentration in relation to digitalis toxicity in neonates and infants.Pediatrics 61:184–188 (1978).PubMedGoogle Scholar
  63. 63c.
    H. Halkin, M. Radomsky, P. Millman, S. Almog, L. Blieden, and H. Boichis. Steady-state serum concentrations and renal clearance of digoxin in neonates, infants and children.Eur. J. Clin. Pharmacol. 13:113–117 (1978).PubMedGoogle Scholar
  64. 64c.
    H. Halkin, L. B. Sheiner, C. C. Peck, and K. L. Melmon, Determinants of the renal clearance of digoxin.Clin. Pharmacol. Ther. 17:385–394 (1975).PubMedGoogle Scholar
  65. 65c.
    G. Hartel, K. Kyllonen, E. Merikallio, K. Ojala, V. Manninen, and P. Reissell. Human serum and myocardial digoxin.Clin. Pharmacol. Ther. 19:153–157 (1976).PubMedGoogle Scholar
  66. 66c.
    C. J. Hayes, V. P. Butler, and W. M. Gersony. Serum digoxin studies in infants and children.Pediatrics 52:561–568 (1973).PubMedGoogle Scholar
  67. 67c.
    W. D. Heizer, T. W. Smith, and S. E. Goldfinger. Absorption of digoxin in patients with malabsorption syndromes.N. Engl. J. Med. 285:257–259 (1971).PubMedGoogle Scholar
  68. 68c.
    P. H. Hinderung. Comparative studies of the protein binding of digoxin and its metabolites,Agents and Actions 7:379–382 (1977).Google Scholar
  69. 69c.
    P. H. Hinderling, E. R. Garrett, and R. C. Wester. Pharmacokinetics ofα-Methyldigoxin in healthy humans I: intravenous studies.J. Pharm. Sci. 66:242–253 (1977).PubMedGoogle Scholar
  70. 70c.
    J. D. Hobson and A. Zettner. Digoxin serum half-life following suicidal digoxin posoning.J. Am. Med. Assoc. 223:147–149 (1973).Google Scholar
  71. 71c.
    J. L. Holtzman, R. B. Shafer, and R. R. Erickson. Methodological causes of discrepancies in radioimmunoassay for digoxin in human serum.Clin. Chem. 20:1194–1198 (1974).PubMedGoogle Scholar
  72. 72c.
    D. Howard, C. Smith, G. Stewart, M. Vadas, D. Tiller, W. Hensley, and J. Richards. A prospective survey of the incidence of cardiac intoxication with digitalis in patients being admitted to hospital and correlation with serum digoxin levels.Aust. N.Z. J. Med. 3:279–284 (1973).PubMedGoogle Scholar
  73. 73c.
    D. H. Huffman. Relationship between digoxin concentrations in serum and saliva.Clin. Pharmacol. Ther. 17:310–312 (1975).PubMedGoogle Scholar
  74. 74c.
    D. Huffman, J. Crow, P. Pentikainen and D. Azarnoff. Association between clinical cardiac status laboratory parameters and digoxin usage.Am. Heart J. 91:28–34 (1976).PubMedGoogle Scholar
  75. 75c.
    D. Huffman, C. Klaassen, and C. Hartman. Digoxin in hyperthyroidism.Clin. Pharmacol. Ther. 22:533–538 (1977).PubMedGoogle Scholar
  76. 76c.
    D. Huffman, C. Manion, and D. Azarnoff. Absorption of digoxin from different oral preparations in normal subjects during steady state,Clin. Pharmacol. Ther. 16:310–317 (1974).PubMedGoogle Scholar
  77. 77c.
    D. Huffman, C. V. Manion, and D. Azarnoff. Intersubject variation in absorption of digoxin in normal volunteers,J. Pharm. Sci. 64:433–137 (1975).PubMedGoogle Scholar
  78. 78c.
    E. Iisalo. Clinical pharmacokinetics of digoxin.Clin. Pharmacokin. 2:1–16 (1977).Google Scholar
  79. 79c.
    E. Iisalo, M. Dahl, and H. Sundqvist. Serum digoxin in adults and children.Int. J. Clin. Pharmacol. 7:219–222 (1973).PubMedGoogle Scholar
  80. 80c.
    B. F. Johnson, and C. Bye. Maximal intestinal absorption of digoxin and its relation to steady-state plasma concentration.Br. Heart J. 37:203–208 (1975).PubMedCentralPubMedGoogle Scholar
  81. 81c.
    B. F. Johnson, C. Bye, and S. Lader. The bioavailability of other digoxin preparations compared with tablets.Postgrad. Med. J. 50(Suppl 6):62–66 (1974).PubMedGoogle Scholar
  82. 82c.
    B. F. Johnson, C. Bye, G. Jones, and G. Sabey. A completely absorbed oral preparation of digoxin.Clin. Pharmacol. Ther. 19:746–751 (1976).PubMedGoogle Scholar
  83. 83c.
    B. F. Johnson, J. O'Grady, and C. Bye. The influence of digoxin particle size on absorption of digoxin and the effect of propantheline and metoclopramide.Br. J. Clin. Pharmacol. 5:465–467 (1978).PubMedCentralPubMedGoogle Scholar
  84. 84c.
    B. F. Johnson, J. O'Grady, G. Sabey, and C. Bye. Effect of a standard breakfast on digoxin absorption in normal subjects.Clin. Pharmacol. Ther. 23:315–319 (1978).PubMedGoogle Scholar
  85. 85c.
    C. I. Johnston, N. B. Pinkus, and M. Down. Plasma digoxin levels in digitalized and toxic patients.Med. J. Aust. 1:863–866 (1972).PubMedGoogle Scholar
  86. 86c.
    G. D. Johnston and D. G. McDevitt. Letter to the editor. Variations of plasma digoxin concentrations in the equilibrium state after multiple dosing.Br. J. Clin. Pharmacol. 5:92–93 (1987).Google Scholar
  87. 87c.
    P. H. Joubert, F. O. Muller, and B. N. Ancomp. Salivary digoxin concentrations.Br. J. Clin. Pharmacol. 3:673–674 (1976).PubMedCentralPubMedGoogle Scholar
  88. 88c.
    R. P. Juhl, R. Summers, J. Guillory, S. Blaug, and F. Cheng. Effect of sulfasalazine on digoxin bioavailability.Clin. Pharmacol. Ther. 20:387–394 (1976).PubMedGoogle Scholar
  89. 89c.
    W. J. Jusko, S. J. Szefler, and A. Goldfarb. Pharmacokinetic design of digoxin dosage regimens in relation to renal function.J. Clin. Pharmacol. 14:525–535 (1974).PubMedGoogle Scholar
  90. 90c.
    W. J. Jusko and M. Weintraub. Myocardial distribution of digoxin and renal function.Clin. Phnarmacol. Ther. 16:449–454 (1974).Google Scholar
  91. 91c.
    J. Karjalainen, K. Ojala, and P. Reissell. Tissue concentrations of digoxin in an autopsy material.Acta Pharmacol. Toxicol. 34:385 (1974).Google Scholar
  92. 92c.
    F. Keller, H. P. Blumenthal, K. Maertin, and N. Rietbrock. Overall pharmacokinetics during prolonged treatment of healthy volunteers with digoxin andα-methyldigoxin.Eur. J. Clin. Pharmacol. 12:387–392 (1977).PubMedGoogle Scholar
  93. 93c.
    F. Keller and N. Rietbrock. Bioavailability of digoxin: some pitfalls and problems.Int. J. Clin. Pharmacol. Biopharm. 15:549–556 (1977).PubMedGoogle Scholar
  94. 94c.
    P. W. Kin, R. W. Krasula, L. F. Soyka, and A. R. Hastreiter. Postmortem tissue digoxin concentrations in infants and children.Circulation 52:1128–1131 (1975).Google Scholar
  95. 95c.
    U. Klotz and K. H. Antonim. Biliary excretion studies with digoxin in man.Int. J. Clin. Pharmacol 15:332–334 (1977).Google Scholar
  96. 96c.
    A. J. Kolbash, W. G. Kramer, R. H. Reuning, and J. H. Caldwell. Marked decline in serum digoxin concentrations during an episode of severe diarrhea.Am. Heart J. 94:906–907 (1977).Google Scholar
  97. 97c.
    J. R. Koup, D. J. Greenblatt, W. J. Jusko, T. W. Smith, and J. Koch-Weser. Pharmacokinetics of digoxin in normal subjects after intravenous bolus and infusion doses.J. Pharmacokin. Biopharm. 3:181–192 (1975).Google Scholar
  98. 98c.
    J. R. Koup, W. J. Jusko, C. M. Elwood, and R. K. Kohli. Digoxin pharmacokinetics: role of renal failure in dosage regimen design.Clin. Pharmacol. Ther. 18:9–21 (1975).PubMedGoogle Scholar
  99. 99c.
    W. G. Kramer, A. J. Kolibash, R. P. Lewis, M. S. Bathala, J. A. Visconti, and R. H. Reuning. Pharmacokinetics of digoxin: relationship between response intensity and predicted compartmental drug levels in man.J. Pharmacokin. Biopharm. 7:47–61 (1979).Google Scholar
  100. 100c.
    W. G. Kramer, R. P. Lewis, T. C. Cobb, W. F. Forester, J. A. Visconti, L. A. Wanke, H. G. Boxenbaum, and R. H. Reuning. Pharmacokinetics of digoxin: comparison of a two- and a three-compartment model in man.J. Pharmacokin. Biopharm. 2:299–312 (1974).Google Scholar
  101. 101c.
    J. R. Lawrence, D. J. Summer, W. J. Kalk, W. A. Ratcliffe, B. Whiting, K. Gray, and M. Lindsay. Digoxin kinetics in patients with thyroid dysfunction.Clin. Pharmacol. Ther. 22:7–13 (1977).PubMedGoogle Scholar
  102. 102c.
    E. B. Leahey, J. A. Reiffel, R. E. Drusin, R. H. Heissenbuttel, W. P. Lovejoy, and J. T. Bigger. Interaction between quinidine and digoxin.J. Am. Med. Assoc. 240:533–534 (1978).Google Scholar
  103. 103c.
    J. Lichey, C. Havestatt, J. Weinmann, J. Hasford and N. Rietbrock. Human myocardium and plasma digoxin concentration in patients on lobg-term digoxin therapy.Int. J. Clin. Pharmacol. Biopharm. 16:460–462 (1978).PubMedGoogle Scholar
  104. 104c.
    J. Lichey, R. Schroder, and N. Rietbrock. The effect of oral spironolactone and intravenous canrenoate-K on the digoxin radioimmunoassay.Int. J. Clin. Pharmacol. 15:557–559 (1977).Google Scholar
  105. 105c.
    J. Lindenbaum. Bioavailability of different lots of digoxin tablets from the same manufacturer.Clin. Pharmacol. Ther. 17:296–301 (1975).PubMedGoogle Scholar
  106. 106c.
    J. Lindenbaum. Greater bioavailability of digoxin solution in capsules.Clin. Pharmacol. Ther. 21:278–282 (1976).Google Scholar
  107. 107c.
    J. Lindenbaum, V. P. Butler, Jr, J. E. Murphy,et al. Correlation of digoxin-tabletdissolution-rate with biological availability.Lancet I:1215–1217 (1973).Google Scholar
  108. 108c.
    J. Lindenbaum, R. M. Maulitz, and V. P. Butler. Inhibition of digoxin absorption by neomycin.Gastroenterology 71:399–404 (1976).PubMedGoogle Scholar
  109. 109c.
    J. Lindenbaum, M. H. Mellow, M. O. Blackstone, and V. P. Butler. Variation in biologic availability of digoxin from four preparations.N. Engl. J. Med. 285:1344–1347 (1971).PubMedGoogle Scholar
  110. 110c.
    B. L. Lloyd, D. J. Greenblatt, M. D. Allen, J. S. Harmatz, and T. W. Smith. Pharmacokinetics and bioavailability of digoxin capsules, solution and tablets after single and multiple doses.Am. J. Cardiol 42:129–135 (1978).PubMedGoogle Scholar
  111. 111c.
    M. W. Loes, S. Singh, J. E. Nock, and B. L. Mirkin. Relation between plasma dn red-cell electrolyte concentrations and digoxin levels in children.N. Engl. J. Med. 299:501–504 (1978).PubMedGoogle Scholar
  112. 112c.
    S. B. Lucas. Can digoxin dose requirements be predicted?Br. J. Clin. Pharmacol. 3:231–237 (1976).PubMedCentralPubMedGoogle Scholar
  113. 113c.
    R. J. Luchi and J. W. Gruber. Unusually large digitalis requirements.Am. J. Med. 45:322–328 (1968).PubMedGoogle Scholar
  114. 114c.
    A. A. MacKinney, G. H. Burnett, R. L. Conklin, and G. W. Wasson. Comparison of five radioimmunoassays and enzyme bioassay for measurement of digoxin in blood.Clin. Chem. 21:857–859 (1975).PubMedGoogle Scholar
  115. 115c.
    A. D. Malcolm, F. Y. Leung, J. C. A. Fuchs, and J. E. Duarte, Digoxin kinetics during furosemide administration.Clin. Pharmacol. Ther. 21:567–574 (1977).PubMedGoogle Scholar
  116. 116c.
    G. I. Mallis, D. H. Schmidt, and J. Lindenbaum. Superior bioavailability of digoxin solution in capsules.Clin. Pharmacol. Ther. 18:761–768 (1975).PubMedGoogle Scholar
  117. 117c.
    V. Manninen, A. Apajalahti, J. Melin, and M. Karesoja. Altered absorption of digoxin in patients given propantheline and metoclopramide.Lancet I:398–400 (1973).Google Scholar
  118. 118c.
    F. I. Marcus, A. Peterson, A. Salel, J. Scully, and G. G. Kapadia. The metabolism of tritiated digoxin in renal insufficiency in dogs and man.J. Pharmacol. Exp. Ther. 152:372–382 (1965).Google Scholar
  119. 119c.
    F. I. Marcus, J. Dickerson, S. Pippin, M. Stafford, and R. Bressler. Digoxin bioavailability: formulations and rates of infusions.Clin. Pharmacol. Ther. 20:253–259 (1976).PubMedGoogle Scholar
  120. 120c.
    R. M. McCredie, B. L. Chia, and P. W. Knight. Infant versus adults plasma digoxin levels.Aust. N.Z. J. Med. 4:223–227 (1974).PubMedGoogle Scholar
  121. 121c.
    P. L. Morselli, B. M. Assael, R. Gomeni, M. Mandelli, A. Marini, E. Reali, U. Visconti, and F. Sereni.Digoxin Pharmacokinetics During Human Development, Raven Press, New York, 377–392 1975, pp. 377–392.Google Scholar
  122. 122c.
    W. B. Nelp. Relationship of the excretion of tritiated digoxin to renal function.Am. J. Med. Sci. 251:133–144 (1966).PubMedGoogle Scholar
  123. 123c.
    J. M. Neutze, J. D. Rutherford, and P. J. Hurley. Serum digoxin levels in neonates, infants and children with heart disease.N.Z. Med. J. 86:7–10 (1977).PubMedGoogle Scholar
  124. 124c.
    P. Neuvonen, S. Elfving, and E. Elonen. Reduction of absorption of digoxin, phenytoin and aspirin by activated charcoal in man.Eur. J. Clin. Pharmacol. 13:213–218 (1978).PubMedGoogle Scholar
  125. 125c.
    L. Nybert, K. Andersson, and A. Bertler. Bioavailability of digoxin from tablets.Acta Pharmacol. Suec. 11:459–470 (1974).Google Scholar
  126. 126c.
    J. O'Grady, B. F. Johnson, C. Bye, and G. A. Sabey. Influence of soft gelatin on digoxin absorption.Br. J. Clin. Pharmacol. 5:461–463 (1978).PubMedCentralPubMedGoogle Scholar
  127. 127c.
    H. Ochs, G. Bodem, P. Schafer, G. Kodrat, and H. Dengler. Absorption of digoxin from the distal parts of the intestine in man.Eur. J. Clin. Pharmacol. 9:95–97 (1975).PubMedGoogle Scholar
  128. 128c.
    H. R. Ochs, D. J. Greenblatt, G. Bodem, and J. S. Harmatz. Dose-independent pharmacokinetics of digoxin in humans.Am. Heart J. 96:507–511 (1978).PubMedGoogle Scholar
  129. 129c.
    E. Ohnhaus, P. Spring, and L. Dettli. Protein binding of digoxin in human serum.Eur. J. Clin. Pharmacol. 5:34–36 (1972).Google Scholar
  130. 130c.
    E. E. Ohnhaus, S. Vozeh, and E. Nuesch. Absorption of digoxin in severe right heart failure.Eur. J. Clin. Pharmacol. 15:115–120 (1979).PubMedGoogle Scholar
  131. 131c.
    R. D. Okada, W. D. Hager, P. E. Graves, M. Mayersohn, D. G. Perrier, and F. I. Marcus. Relationship between plasma-concentration and dose of digoxin in patients with and without renal impairment.Circulation 58:1196–1203 (1978).PubMedGoogle Scholar
  132. 132c.
    G. C. Oliver, B. M. Parker, and C. W. Parker. Radioimmunoassay for digoxin.Am. J. Med. 51:186–192 (1971).PubMedGoogle Scholar
  133. 133c.
    M. F. Paulson, and P. G. Welling. Calculation of serum digoxin levels in patients with normal and impaired renal function.J. Clin. Pharmacol. 16:660–665 (1976).PubMedGoogle Scholar
  134. 134c.
    U. Peters, I. C. Falk, and S. M. Kalman. Digoxin metabolism in patients.Arch. Intern. Med. 138:1074–1076 (1978).PubMedGoogle Scholar
  135. 135c.
    J. J. Preibisz, V. P. Butler, and J. Lindenbaum. Digoxin tablet bioavailability: single dose and steady-state assessment.Ann. Intern. Med. 81:469–474 (1974).PubMedGoogle Scholar
  136. 136c.
    S. W. Rabkin, and G. Grupp. A two compartment open model for digoxin pharmacokinetics in patients receiving a wide range of digoxin doses.Acta Cardiol. 30:343–351 (1975).PubMedGoogle Scholar
  137. 137c.
    A. Redfors, A. Bertler, and H. Schuller. The ratio between myocardial and plasma levels of digoxin in man.Symposium on Digitalis, 1973, pp. 265–269.Google Scholar
  138. 138c.
    R. H. Reuning, R. A. Sams, and R. E. Notari. Role of pharmacokinetics in drug dosage adjustment. 1. Pharmacologic effect kinetics and apparent volume of distribution of digoxin.J. Clin. Pharmacol. 13:127–141 (1973).Google Scholar
  139. 139c.
    E. M. Rodgers, S. M. Dobbs, W. I. Kenyon, and J. W. Poston. Evaluation of digoxin capsules in outpatients.Br. Med. J. 2:234–235 (1977).PubMedCentralPubMedGoogle Scholar
  140. 140c.
    M. C. Rogers, J. T. Willerson, A. Goldblatt, and T. W. Smith. Serum digoxin concentrations in the human fetus, neonate and infant.N. Engl. J. Med. 287:1010–1013 (1972).PubMedGoogle Scholar
  141. 141c.
    A. F. Rosenthal, M. G. Vargas, and C. S. Klass. Evaluation of enzyme-multiplied immunoassay technique (EMIT) for determination of serum digoxin.Clin. Chem. 22:1899–1902 (1976).PubMedGoogle Scholar
  142. 142c.
    N. Sanchez, L. Sheiner, H. Halkin, and K. Melmon. Pharmacokinetics of digoxin: interpreting bioavailability.Br. Med. J. 4:132–134 (1974).Google Scholar
  143. 143c.
    A. Schinz, K. Schnelle, G. Klein, and H. Blomer. Time sequence of direct vascular and inotropic effects following intravenous administration of digoxin in normal man.Int. J. Clin. Pharmacol. 15:189–193 (1977).Google Scholar
  144. 144c.
    J. Schneider, and A. Ruiz. Digitalis effect and blood concentration.Int. J. Clin. Pharmacol. 15:424–427 (1977).Google Scholar
  145. 145c.
    W. Shapiro. Correlative studies of serum digitalis levels and the arrhythmias of digitalis intoxication.Am. J. Cardiol. 41:852–859 (1978).PubMedGoogle Scholar
  146. 146c.
    W. Shapiro, K. Narahara, and K. Taubert. Relationship of plasma digitoxin and digoxin to cardiac response following intravenous digitalization in man.Circulation 42:1065–1073 (1970).PubMedGoogle Scholar
  147. 147c.
    L. B. Sheiner, H. Halkin, C. Peck, B. Rosenberg, and K. L. Melmon. Improved computer-assisted digoxin therapy. A method using feedback of measured serum digoxin concentrations.Ann. Intern. Med. 82:619–627 (1975).PubMedGoogle Scholar
  148. 148c.
    L. B. Sheiner, B. Rosenberg, and V. Marathe. Estimation of population characteristics of pharmacokinetic parameters from routine clinical data.J. Pharmacokin. Biopharm. 5:445–479 (1977).Google Scholar
  149. 149c.
    G. M. Shenfield, J. Thompson, and D. B. Horn. Plasma and urinary digoxin in thyroid dysfunction.Eur. J. Clin. Pharmacol. 12:437–443 (1977).PubMedGoogle Scholar
  150. 150c.
    T. W. Smith, V. P. Butler, and E. Haber, Determination of therapeutic and toxic serum digoxin concentrations by radioimmunoassay.N. Engl. J. Med. 281:1212–1216 (1969).PubMedGoogle Scholar
  151. 151c.
    T. W. Smith and E. Haber. Digoxin intoxication: the relationship of clinical presentation to serum digoxin concentration.J. Clin. Invest. 49:2377–2386 (1970).PubMedCentralPubMedGoogle Scholar
  152. 152c.
    E. Steiness. Renal tubular secretion of digoxin.Circulation 50:103–107 (1974).PubMedGoogle Scholar
  153. 153c.
    E. Steiness. Suppression of renal excretion of digoxin in hypokalemic patients.Clin. Pharmacol. Ther. 23:511–514 (1978).PubMedGoogle Scholar
  154. 154c.
    R. G. Stoll, M. S. Christensen, E. Sakmar, and J. G. Wagner. The specificity of the digoxin radioimmunoassay procedure.Res. Comm. Chem. Pathol. Pharmacol. 4:503–510 (1972).Google Scholar
  155. 155c.
    L. Storstein. Studies on digitalis. V. The influence of impaired renal function, hemodialysis, and drug interaction on serum protein binding of digitoxin and digoxin.Clin. Pharmacol. Ther. 20:6–14 (1976).PubMedGoogle Scholar
  156. 156c.
    D. Sumner and A. Russel. Digoxin pharmacokinetics: multicompartmental analysis and its clinical implications.Br. J. Clin. Pharmacol. 3:221–229 (1976).PubMedCentralPubMedGoogle Scholar
  157. 157c.
    S. J. Szefler, J. R. Koup, and G. P. Giacoia. Paradoxical behavior of serum digoxin concentrations in an anuric neonate.J. Pediatr. 91:487–489 (1977).PubMedGoogle Scholar
  158. 158c.
    W. J. Tilstone, P. Semple, D. Lawson, and J. Boyle. Effects of furosemide on glomerular filtration rate and clearance of practalol, digoxin, cephaloridine, and gentamicin.Clin. Pharmacol. Ther. 22:389–394 (1977).PubMedGoogle Scholar
  159. 159c.
    J. G. Wagner. Pharmacokinetic paameters estimated from intravenous data by uniform methods and some of their uses.J. Pharmacokin. Biopharm. 5:161–182 (1977).Google Scholar
  160. 160c.
    J. G. Wagner, M. Christensen, E. Sakmar, D. Blair, J. Yates, P. Willis, A. Sedman, and R. Stoll. Equivalence lack in digoxin plasma levels.J. Am. Med. Assoc. 224:199–204 (1973).Google Scholar
  161. 161c.
    J. G. Wagner, J. D. Yates, P. W. Willis, F. Sakmar, and R. Stoll. Correlation of plasma levels of digoxin in cardiac patients with dose and measures of renal function.Clin. Pharmacol. Ther. 15:291–301 (1974).PubMedGoogle Scholar
  162. 162c.
    S. Waldorff and J. Buch. Serum digoxin and empiric methods in identification of digitoxicity.Clin. Pharmacol. Ther. 23:19–24 (1978).PubMedGoogle Scholar
  163. 163c.
    S. Waldorff, J. Damgaard Andersen, N., Heeboll-Nielsen, O. Gamborg-Nielsen, E. Moltke, U. Sorensen, and E. Steiness. Spironolactone-induced changes in digoxin kinetics.Clin. Pharmacol. Ther. 24:162–167 (1978).PubMedGoogle Scholar
  164. 164c.
    S. Wallace, and B. Whiting. Some clinical implications of the protein binding of digoxin.Br. J. Clin. Pharmacol. 1:325–328 (1974).PubMedCentralPubMedGoogle Scholar
  165. 165c.
    E. Watson, D. Clark, and S. Kalman. Identification by gas chromatography mass spectroscopy of dihydrodigoxin—a metabolite of digoxin in man.J. Pharmacol. Exp. Ther. 184:424–431 (1972).Google Scholar
  166. 166c.
    G. Wettrell. Distribution and elimination of digoxin in infants.Eur. J. Clin. Pharmacol. 11:329–335 (1977).PubMedGoogle Scholar
  167. 167c.
    G. Wettrell and K. E. Andersson. Absorption of digoxin in infants.Eur. J. Clin. Pharmacol. 9:49–55 (1975).PubMedGoogle Scholar
  168. 168c.
    F. Wettrell, K. E. Andersson, and L. Nyberg. Effect of exchange transfusion on the elimination of digoxin in neonates.Eur. J. Clin. Pharmacol. 10:25–29 (1976).Google Scholar
  169. 169c.
    R. White, D. Chamberlain, M. Howard, and T. Smith. Plasma concentrations of digoxin after oral administration in the fasting and postprandial state.Br. Med. J. 1:380–381 (1971).PubMedCentralPubMedGoogle Scholar

Digoxin: supplementary references

  1. 170c.
    J. K. Aronson and D. G. Grahame-Smith. Digoxin therapy: textbooks, theory, and practice.Br. J. Clin. Pharmacool. 3:639–648 (1976).Google Scholar
  2. 171c.
    J. K. Aronson and D. G. Graham-Smith. Altered distribution of digoxin in renal failure-a cause of digoxin toxicity?Br. J. Clin. Pharmacol. 3:1045–1051 (1976).PubMedCentralPubMedGoogle Scholar
  3. 172c.
    A. B. T. J. Boink, H. H. Druyswijk, A. F. Willebrands, and A. H. J. Maas. Some factors affecting a commercial kit for radioimmunoassay of digoxin using tritiated digoxin.J. Clin. Chem. Clin. Biochem. 15:261–266 (1977).PubMedGoogle Scholar
  4. 173c.
    V. P. Butler and J. Lindenbaum. Serum digitalis measurements in the assessment of digitalis resistance and sensitivity.Am. J. Med. 58:460–469 (1975).PubMedGoogle Scholar
  5. 174c.
    D. A. Chamberlain, R. J. White, M. R. Howard, and T. W. Smith. Plasma digoxin concentrations in patients with atrial fibrillation.Br. Med. J. 3:429–432 (1970).PubMedCentralPubMedGoogle Scholar
  6. 175c.
    P. S. Collier, D. W. G. Harron, and K. R. Devine, Pharmacokinetic profile of oral digoxin in healthy volunteers,Int. J. Pharmacol. 1:3–14 (1978).Google Scholar
  7. 176c.
    A. Danon, J. Horowitz, Z. Ben-Zvi, J. Kaplanski, and S. Glick. An outbreak of digoxin intoxication.Clin. Pharmacol. Ther. 21:643–646 (1977).PubMedGoogle Scholar
  8. 177c.
    S. M. Dobbs and G. E. Mawer. Prediction of digoxin dose requirements.Clin. Pharmacokin. 2:281–291 (1977).Google Scholar
  9. 178c.
    S. M. Dobbs, E. M. Rodgers, and G. E. Mawer. Serum digoxin concentrations.Br. J. Clin. Pharmacol. 3:674–676 (1976).PubMedCentralPubMedGoogle Scholar
  10. 179c.
    J. E. Doherty. The clinical pharmacology of digitalis glycosides.Am. J. Med. Sci. 255:382–414 (1968).PubMedGoogle Scholar
  11. 180c.
    J. E. Doherty, W. H. Perkins, and W. H. Flanigan. The distribution and concentration of tritiated digoxin in human tissues.Ann. Intern. Med. 66:116–124 (1967).PubMedGoogle Scholar
  12. 181c.
    J. E. Doherty, W. H. Perkins, and M. C. Wilson. Studies with tritiated digoxin in renal failure.Am. J. Med. 37:536–544 (1964).PubMedGoogle Scholar
  13. 182c.
    D. W. Duhme, D. J. Greenblatt, and J. Koch-Weser. Reduction of digoxin toxicity associated with measurement of serum levels.Ann. Intern. Med. 80:516–519 (1974).PubMedGoogle Scholar
  14. 183c.
    D. J. Greenblatt, D. W. Duhme, J. Koch-Weser, and T. W. Smith. Assessment of methodology in single-dose studies of digoxin bioavailability.Pharmacol. 14:182–190 (1976).Google Scholar
  15. 184c.
    L. I. Harrison and M. Gibaldi. Physiologically based pharmacokinetic model for digoxin disposition in dogs and its preliminary application to humans.J. Pharm. Sci. 66:1679–1683 (1977).PubMedGoogle Scholar
  16. 185c.
    R. P. Hayward, H. Greenwood, and J. Hamer. Comparison of digoxin and medigoxin in normal subjects.Br. J. Clin. Pharmacol. 6:81–86 (1978).PubMedCentralPubMedGoogle Scholar
  17. 186c.
    N. Heinz and N. Rietbrock. Relationship between dose and plasma level of digoxin and patient characteristics.Eur. J. Clin. Pharmacol. 15:109–114 (1979).PubMedGoogle Scholar
  18. 187c.
    D. H. Huffman and D. L. Azarnoff. Absorption of orally given digoxin preparations.J. Am. Med. Assoc. 222:957–960 (1972).Google Scholar
  19. 188c.
    D. H. Huffman, J. W. Crow, P. Pentikainen, and D. L. Azarnoff. Association between clinical cardiac status, laboratory parameters and digoxin usage.Am. Heart J. 91:28–34 (1976).PubMedGoogle Scholar
  20. 189c.
    J. A. Ingelfinger and P. Goldman. The serum digitalis concentration-does it diagnose digitalis toxicity?N. Engl. J. Med. 294:867–870 (1976).PubMedGoogle Scholar
  21. 190c.
    R. W. Jelliffe. A mathematical analysis of digitalis kinetics in patients with normal and reduced renal function.Math. Biosci. 1:305–3325 (1967).Google Scholar
  22. 191c.
    R. W. Jelliffe. An improved method of digoxin therapy. Ann.Intern. Med. 69:703–717 (1968).PubMedGoogle Scholar
  23. 192c.
    R. W. Jelliffe. Administration of digoxin.Dis. Chest 56:56–60 (1969).PubMedGoogle Scholar
  24. 193c.
    B. J. Johnson and S. Lader. Bioavailability of digoxin from rapidly dissolving preparations.Br. J. Clin. Pharmacol. 1:329–333 (1974).PubMedCentralPubMedGoogle Scholar
  25. 194c.
    F. Keller and N. Rietbrock. Bioavailability of digoxin: some pitfalls and problems.Int. J. Clin. Pharmacol. 15:549–556 (1977).Google Scholar
  26. 195c.
    J. Koch-Weser, D. W. Duhme, and D. J. Greenblatt. Influence of serum digoxin concentration measurements on frequency of digitoxicity.Clin. Pharmacol. Ther. 16:284–287 (1974).PubMedGoogle Scholar
  27. 196c.
    P. Kramer. Digitalis pharmacokinetics and therapy with respect to impaired renal function.Klin. Wschr. 55:1–11 (1977).PubMedGoogle Scholar
  28. 197c.
    W. G. Kramer, A. J. Kolibash, M. S. Bathala, J. A. Visconti, R. P. Lewis, and R. H. Reuning. Digoxin bioavailability: evaluation of a generic tablet and proposed FDA guidelines.J. Pharm. Sci. 66:1720–1722 (1977).PubMedGoogle Scholar
  29. 198c.
    J. C. K. Loo, I. J. McGilveray, and N. Jordan. Quantitation of digoxigenin in serum following oral administration of digoxin in humans.Res. Comm. Chem. Pathol. Pharmacol. 17:497–506 (1977).Google Scholar
  30. 199c.
    A. Malcolm and J. Coltart. Relation between concentrations of digoxin in the myocardium and in the plasma.Br. Heart J. 39:935–938 (1977).PubMedCentralPubMedGoogle Scholar
  31. 200c.
    A. D. Malcolm, F. Y. Leung, J. C. A. Fuchs, and J. E. Duarte. Digoxin kinetics during furosemide administration.Clin. Pharmacol. Ther. 21:567–574 (1977).PubMedGoogle Scholar
  32. 201c.
    V. Manninen, P. Reissell, and E. Paukkala. Transient cardiac arrhythmias after single daily maintenance doses of digoxin.Clin. Pharmacol. Ther. 20:266–268 (1976).PubMedGoogle Scholar
  33. 202c.
    J. O'Grady, B. F. Johnson, C. Bye, and J. French. The comparative bioavailability of lanoxin* tablets and lanoxicaps* with and without sorbitol.Eur. J. Clin. Pharmacol. 14:357–360 (1978).PubMedGoogle Scholar
  34. 203c.
    L. Padeletti and A. Brat. Bioavailability of digoxin in capsules.Int. J. Clin. Pharmacol. 16:320–322 (1978).Google Scholar
  35. 204c.
    I. Rietbrock. Prediction of pharmacokinetic behavior of digitalis glycosides in patients under intensive care conditions and in patients undergoing anaesthesia and operation.Anaesthetist 27:151–162 (1978).Google Scholar
  36. 205c.
    S. K. Sim. Digoxin tablets, a review of the bioavailability problems.Am. J. Hosp. Pharm. 33:44–48 (1976).PubMedGoogle Scholar
  37. 206c.
    T. W. Smith. Contribution of quantitative assay technic to the understanding of the clinical phamacology of digitalis.Circulation 46:188–199 (1972).PubMedGoogle Scholar
  38. 207c.
    T. W. Smith, E. Haber, L. Yeatman, and V. P. Butler. Reversal of advanced intoxication with Fab fragments of digoxin-specific antibodies.N. Engl. J. Med. 294:797–800 (1976).PubMedGoogle Scholar
  39. 208c.
    E. Tsutsumi, H. Fujiki, H. Takeda, and H. Fukushima. Effect of furosemide on serum clearance and renal excretion of digoxin.J. Clin. Pharmacol. 19:200–204 (1979).PubMedGoogle Scholar
  40. 209c.
    J. Turner, S. M. Dobbs, P. W. Nicholson, A. P. J. McGill, and E. M. Rodgers. Letter to the Editor. Influence of diet on digoxin dose requirements.Br. J. Clin. Pharmacol. 4:489–492 (1977).PubMedCentralPubMedGoogle Scholar
  41. 210c.
    W. J. F. van der Vigh. Pharmacokinetic aspects of digoxin in patients with terminal renal failure.Int. J. Clin. Pharmacol. 15:249–254 (1977).Google Scholar
  42. 211c.
    W. J. F. van der Vigh and P. L. Oe. Pharmacokinetic aspects of digoxin in patients with terminal renal failure. III. Effect of heparin.Int. J. Clin. Pharmacol. 15:560–562 (1977).Google Scholar
  43. 212c.
    J. G. Wagner. Loading and maintenance doses of digoxin in patients with normal renal function and those with severely impaired renal function.J. Clin. Pharm. 14:329–338 (1974).Google Scholar
  44. 213c.
    J. G. Wagner and J. W. Ayres. Bioavailability assessment: methods to estimate total area and total amount excreted and importance of blood and urine sampling scheme with application to digoxin.J. Pharmacokin. Biopharm. 5:533–557 (1977).Google Scholar
  45. 214c.
    B. Whiting, I. Wandless, D. J. Summer, and A. Goldberg. Computer-assisted review of digoxin therapy in the elderly.Br. Heart J. 40:8–13 (1978).PubMedCentralPubMedGoogle Scholar

Isosorbide references

  1. 1d.
    D. F. Assinder, L. F. Chasseaud, J. O. Hunter, R. J. Jung, and T. Taylor. Plasma concentrations of isosorbide dinitrate after oral administration of a sustained-release formulation to human subjects.Arzneim-Forsch/Drug Res. 27(I):156–158 (1977).Google Scholar
  2. 2d.
    D. F. Assinder, L. F. Chasseaud, and T. Taylor. Plasma isosorbide dinitrate concentrations in human subjects after administration of standard and sustained-release formulations.J. Pharm. Sci. 66:775–778 (1977).PubMedGoogle Scholar
  3. 3d.
    L. F. Chasseaud, W. H. Down, and R. K. Grundy. Concentrations of the vasodilator isosorbide dinitrate and its metabolites in the blood of human subjects.Eur. J. Clin. Pharmacol 8:157–160 (1975).PubMedGoogle Scholar
  4. 4d.
    W. H. Down, L. F. Chasseaud, and R. K. Grundy. Biotransformation of isosorbide dinitrate in humans.J. Pharm. Sci. 63:1147–1149 (1974).PubMedGoogle Scholar
  5. 5d.
    D. Mansel-Jones, T. Taylor, E. Doyle, L. F. Chasseaud, A. Darragh, D. A. O'Kelly, and H. Over. Plasma concentrations of isosorbide dinitrate after cutaneous and sublingual doses to human subjects.J. Clin. Pharmacol. 18:544–548 (1978).PubMedGoogle Scholar
  6. 6d.
    M. T. Rosseel and M. G. Bogaert. GLC determination of nitroglycerin and isosorbide dinitrate in human plasma.J. Pharm. Sci. 62:754–758 (1973).PubMedGoogle Scholar
  7. 7d.
    S. J. Shane, J. J. Iazzetta, A. W. Chisolm, J. F. Berka, and D. Leung. Plasma concentrations of isosorbide dinitrate and its metabolites after chronic high oral dosage in man.Br. J. Clin. Pharmacol. 6:37–41 (1978).PubMedCentralPubMedGoogle Scholar

Nitroglycerin references

  1. 1e.
    P. W. Armstrong, J. A. Armstrong, and G. S. Marks. Blood levels after sublingual nitroglycerin.Circulation 59:585–588 (1979).PubMedGoogle Scholar
  2. 2e.
    H. P. Blumenthal, H.-L. Fung, E. F. McNiff, and S. K. Yap. Plasma nitroglycerin levels after sublingual, oral and topical administration.Br. J. Clin. Pharmacol. 4:241–242 (1977).PubMedCentralPubMedGoogle Scholar
  3. 3e.
    L. J. Cass and W. S. Frederik. The application of new chemical techniques in clinical research of coronary artery disease.Angiology 14:556–558 (1963).PubMedGoogle Scholar
  4. 4e.
    B. Dorsch and R. Shangraw. Stability of stabilized nitroglycerin tablets in typical distribution and administration systems.Am. J. Hosp. Pharm. 32:795–808 (1975).PubMedGoogle Scholar
  5. 5e.
    S. A. Fusari. Nitroglycerin sublingual tabletsI: stability of conventional tablets.J. Pharm. Sci. 62:122–129 (1973).PubMedGoogle Scholar
  6. 6e.
    G. B. Neurath and M. Dunger. Blood levels of the metabolites of glyceryl trinitrate and pentaerythritol tetranitrate after administration of a two-step preparation.Drug Res. 27:416–419 (1977).Google Scholar
  7. 7e.
    M. J. Rossel and M. G. Bogaert. GIC determination of nitroglycerin and isosorbide dinitrate in human plasma.J. Pharm. Sci. 62:754–758 (1973).Google Scholar
  8. 8e.
    W. A. Von Ritchel and R. Clotten. Entwicklung einer peroralen nitroglycerin proxyphyllin-retard-form.Drug Res. 9:1180–1187 (1970).Google Scholar
  9. 9e.
    J. Y. Wei and P. R. Reid. Quantitative determination of trinitroglycerin in human plasma.Circulation 59:588–592 (1979).PubMedGoogle Scholar
  10. 10e.
    P. S. D. Yap, E. F. McNiff, and H.-L. Fung. Improved GLC determination of plasma nitroglycerin concentrations.J. Pharmaceut. Sci. 67:582–584 (1978).Google Scholar

Nitroglycerin: supplementary references

  1. 11e.
    D. M. Baaske, J. E. Carter, and A. H. Amann. Rapid and accurate stability-indicating assay for nitroglycerin.J. Pharmaceut. Sci. 68:481–483 (1979).Google Scholar
  2. 12e.
    W. G. Crouthamel and B. Dorsch. Specific high-performance liquid Chromatographic assay for nitroglycerin in dosage forms.J. Pharmaceut. Sci. 68:237–238 (1979).Google Scholar
  3. 13e.
    G. S. Francis and A. D. Hagan. Nitroglycerin ointment.Angiology 28:873–878 (1977).PubMedGoogle Scholar
  4. 14e.
    Y. Givant and F. G. Sulman. Quantitation of nitroglycerin in human blood after administration by sustained release.Experientia 34:643–644 (1978).PubMedGoogle Scholar
  5. 15e.
    R. F. Shangraw and A. M. Contractor. New developments in the manufacture and packaging of nitroglycerin tablets.J. Am. Pharm. Assoc. 12:633–636 (1972).PubMedGoogle Scholar

Pindolol references

  1. 1f.
    A. Bobik, G. Jennings, and P. I. Korner. Plasma pindolol levels and their significance in the assessment of cardiac beta blockade.Med. J. Aust. 2(2 suppl):3–5 (1977).PubMedGoogle Scholar
  2. 2f.
    N. P. Chau, Y. A. Weiss, M. E. Safar, D. E. Lavene, D. R. Georges, D. E. Lavene, D. R. Georges, and P. L. Milliez. Pindolol availability in hypertensive patients with normal and impaired renal function,Clin. Pharmacol. Ther. 22:505–510 (1977).PubMedGoogle Scholar
  3. 3f.
    R. Gugler and G. Bodem. Single and multiple dose pharmacokinetics of pindolol.Eur. J. Clin. Pharmacol. 13:13–16 (1978).PubMedGoogle Scholar
  4. 4f.
    R. Gugler, W. Herold, and H. J. Dengler. Pharmacokinetics of pindolol in man.Eur. J. Clin. Pharmacol. 7:17–24 (1974).PubMedGoogle Scholar
  5. 5f.
    R. Gugler, W. Hobel, G. Bodem, and H. J. Dengler. The effect of pindolol on exerciseinduced cardiac acceleration in relation to plasma levels in man.Clin. Pharmacol. Ther. 17:127–132 (1978).Google Scholar
  6. 6f.
    D. C. Hicks, A. G. Arbab, P. Turner, and M. Hills. A comparison of intravenous pindolol and propranolol in normal man.J. Clin. Pharmacol. 12:212–216 (1972).Google Scholar
  7. 7f.
    G. L. Jennings, A. Bobik, E. T. Fagan, and P. I. Korner. Pindolol pharmacokinetics in relation to time course of inhibition of exercise tachycardia.Br. J. Clin. Pharmacol. 7:245–256 (1979).PubMedCentralPubMedGoogle Scholar
  8. 8f.
    J. L. Kiger, D. Lavene, M. F. Guillaume, M. Guerret, and J. Longchamp. The effect of food and clopamide on the absorption of pindolol in man.Int. J. Clin. Pharmacol. 13:228–232 (1976).Google Scholar
  9. 9f.
    D. Lavene, Y. A. Weiss, M. E. Safar, Y. Loria, N. Agorus, D. Georges, and P. L. Milliez. Pharmacokinetics and hepatic extraction ratio of pindolol in hypertensive patients with normal and impaired renal function.J. Clin. Pharmacol. 17:501–508 (1977).PubMedGoogle Scholar
  10. 10f.
    J. Meier and E. Nuesch. Pindolol, beta-adrenoceptor blocking agent with a negligible first-pass effect.Br. J. Clin. Pharmacol. 4:371–372 (1977).PubMedCentralPubMedGoogle Scholar
  11. 11f.
    E. E. Ohnhaus, E. Nuesch, J. Meier, and F. Kalberer. Pharmacokinetics of unlabelled and 14C-labelled pindolol in uraemia.Eur. J. Clin. Pharmacol. 7:25–29 (1974).PubMedGoogle Scholar
  12. 12f.
    S. Oie and G. Levy. Relationship between renal function and elimination kinetics of pindolol in man.Eur. J. Clin. Pharmacol. 9:115–116 (1975).PubMedGoogle Scholar
  13. 13f.
    W. L. Pacha. A method for the fluorimetric determination of 4-(2-hydroxy-3-isopropylaminopropoxy)-indole (LB46), a beta-blocking agent, in plasma and urine.Experientia 25:802–803 (1969).PubMedGoogle Scholar
  14. 14f.
    L. A. Salako, A. Ragon, R. A. Adio, and A. O. Falase. Pharmacokinetics of pindolol in Africans.Experientia 35:250–241 (1979).PubMedGoogle Scholar

Pindolol: supplementary references

  1. 15f.
    W. H. Aellig. Beta-adrenoceptor blocking activity and duration of action of pindolol and propranolol in healthy volunteers.Br. J. Clin. Pharmacol. 3:251–257 (1976).PubMedCentralPubMedGoogle Scholar
  2. 16f.
    C. Heierli, H. Thoelen, and P. Radielovic. Renal function following a single dose of pindolol in hypertensive patients with varying degrees of impairment of renal function.Int. J. Clin. Pharmacol. 15:65–71 (1977).Google Scholar
  3. 17f.
    G. Jennings, A. Bobik, and P. I. Korner. Pindolol: exercise testing and angina.Med. J. Aust. 2:6–7 (1977).PubMedGoogle Scholar
  4. 18f.
    R. Lancaster, T. J. Goodwin, and W. S. Peart. The effect of pindolol on plasma renin activity and blood pressure in hypertensive patients.Br. J. Clin. Pharmacol. 3:453–460 (1976).PubMedCentralPubMedGoogle Scholar
  5. 19f.
    J. Meier. Pindolol: a pharmacokinetic comparison with other beta-adrenoceptor blocking agents.Acta. Med. Scand. (suppl. 606):65–70 (1977).Google Scholar
  6. 20f.
    M. E. Safar, N. Chau, J. A. Levenson, A. C. Simon, and Y. A. Weiss. Pharmacokinetics of intravenous and oral pindolol in hypertensive patients with chronic renal failure.Biochem. Sci. Mol. Med. 55:275s-277s (1978).Google Scholar
  7. 21f.
    Y. M. Traub and J. B. Rosenfeld. Once-α-day pindolol in hypertension.Clin. Pharmacol. Ther. 21:588–592 (1976).Google Scholar

Propranolol references

  1. 1g.
    M. R. Achong, M. B. Kenneth, M. Piafsky, and R. I. Ogilvie. Duration of cardiac effects of timolol and propranolol.Clin. Pharmacol. Ther. 19:148–152 (1976).PubMedGoogle Scholar
  2. 2g.
    C. Appelgren, K. O. Borg, R. Elofsson, and K. A. Johansson. Binding of adrenergic beta-receptor antagonists to human serum albumin.Acta. Pharm. Suecica 11:325–332 (1974).Google Scholar
  3. 3g.
    J. M. Bell, C. J. Russell, and J. K. Nelson. Studies of the effect of thyroid dysfunction on the elimination of beta-adrenoceptor blocking drugs.Br. J. Clin. Pharmacol. 4:79–82 (1977).PubMedCentralPubMedGoogle Scholar
  4. 4g.
    G. Bianchetti, G. Graziani, D. Brancaccio, A. Morganti, G. Leonetti, M. Manfrin, R. Sega, R. Gomeni, C. Ponticelli, and P. L. Morselli. Pharmacokinetics and effects of propranolol in terminal uraemic patients and in patients undergoing regular dialysis treatment.Clin. Pharmacokin. 1:373–384 (1976).Google Scholar
  5. 5g.
    J. P. Bilezikian, D. E. Gammon, C. Lee-Rochester, and D. G. Shand. A radioreceptor assay for propranolol.Clin. Pharmacol Ther. 26:173–180 (1979).PubMedGoogle Scholar
  6. 6g.
    O. Borga, K. M. Piafsky, and O. B. Nilsen. Plasma protein binding of basic drugs. I. Selection displacement from alpha-acid glycoprotein by this (2-butoxyethyl) phosphate.Clin. Pharmacol. Ther. 22:539–544 (1977).PubMedGoogle Scholar
  7. 7g.
    H. Boudoulas, B. M. Beaver, R. E. Kates, and R. P. Lewis. Pharmacodynamics of inotropic and chronotropic responses to oral therapy with propranolol.Chest 73:146–153 (1978).PubMedGoogle Scholar
  8. 8g.
    R. A. Branch, J. James, and A. E. Read. The pharmacokinetics of (+) propranolol in normal subjects and patients with chronic liver disease.Br. J. Clin. Pharmacol. 2:183–184 (1975).Google Scholar
  9. 9g.
    R. A. Branch, J. James, and A. E. Read. A study of factors influencing drug disposition in chronic liver disease, using the model drug (+)-propranolol.Br. J. Clin. Pharmacol. 3:243–249 (1976).PubMedCentralPubMedGoogle Scholar
  10. 10g.
    R. A. Branch, D. M. Kornhauser, D. G. Shand, G. R. Wilkinson, and A. J. J. Wood. Biological determinants of propranolol disposition in normal subjects and patients with cirrhosis.Br. J. Clin. Pharmacol. 4:630 (1977).Google Scholar
  11. 11g.
    C. M. Castleden, and C. F. George. The effect of ageing on the hepatic clearance of propranolol.Br. J. Clin. Pharmacol. 7:49–54 (1979).PubMedCentralPubMedGoogle Scholar
  12. 12g.
    C. M. Castleden, C. M. Kaye, and R. L. Parsons. The effect of age on plasma levels of propranolol and practolol in man.J. Clin. Pharmacol. 2:303–306 (1975).Google Scholar
  13. 13g.
    C. Chidsey, M. Pine, L., Favrot, and S. Smith. The use of drug concentration measurements in studies of the therapeutic response to propranolol.Postgraduate Med. J. 52:26–32 (1976).Google Scholar
  14. 14g.
    C. A. Chidsey, P. Morselli, G. Bianchetti, A. Morganti, G. Leonetti, and A. Zanchetti. Studies of the absorption and removal of propranolol in hypertensive patients during therapy.Circulation 52:313–318 (1975).PubMedGoogle Scholar
  15. 15g.
    C. R. Cleaveland and D. G. Shand. Effect of route of administration on the relationship between beta-adrenergic blockade and plasma propranolol level.Clin. Pharmacol. Ther. 13:181–185 (1971).Google Scholar
  16. 16g.
    D. J. Coltart. Plasma propranolol levels in the quantitative assessment of beta-adrenergic blockade in man.Br. Med. J. 3:731–734 (1970).PubMedCentralPubMedGoogle Scholar
  17. 17g.
    R. M. Cotham and D. G. Shand. Spuriously low plasma propranolol concentrations resulting from blood collection methods.Clin. Pharmacol. Ther. 18:535–538 (1975).PubMedGoogle Scholar
  18. 18g.
    R. Davies, A. Morganti, P. L. Morselli, T. G. Pickering, G. Bianchetti, J. Romankiewicz, and J. H. Laragh. Beta-blockade and blood levels after low-dose oral propranolol: the hepatic “first-pass” threshold revisited.Lancet I:407–410 (1978).Google Scholar
  19. 19g.
    A. Di Salle, K. M. Baker, S. R. Bareggi, W. D. Watkins, C. A. Chidsey, A. Brigerio, and P. L. Morselli. A sensitive gas Chromatographic method for the determination of propranolol in human plasma.J. Chromatogr. 84:347–353 (1973).PubMedGoogle Scholar
  20. 20g.
    M. Esler, A. Zweifler, O. Randall, and V. DeQuattro. Pathophysiologic and pharmacokinetic determinants of the antihypertensive response to propranolol.Clin. Pharmacol. Ther. 22:299–308 (1977).PubMedGoogle Scholar
  21. 21g.
    G. H. Evans, A. S. Nies, and D. G. Shand. The disposition of propranolol. III. Decreased half-life and volume of distribution as a result of plasma binding in man, monkey, dog and rat.J. Pharmacol. Exp. Ther. 186:114–122 (1973).PubMedGoogle Scholar
  22. 22g.
    G. H. Evans and D. G. Shand. Disposition of propranolol. V. Drug accumulation and steady-state concentrations during chronic oral administration in man.Clin. Pharmacol. Ther. 14:487–493 (1970).Google Scholar
  23. 23g.
    G. H. Evans and D. G. Shand. Disposition of propranolol VI. Independent variation in steady-state circulating drug concentrations and half-life as a result of plasma drug binding in man.Clin. Pharmacol. Ther. 14:494–500 (1970).Google Scholar
  24. 24g.
    J. D. Fitzgerald and S. R. O'Donnell. Pharmacology of 4-hydroxypropranolol, a metabolite of propranolol.Br. J. Pharmacol. 43:222–235 (1971).PubMedCentralPubMedGoogle Scholar
  25. 25g.
    F. Giudicelli, C. Richer, M. Chauvin, N. Idrissi, and A. Berdeaux. Comparative betaadrenoceptor blocking effects and pharmacokinetics of penbutolol and propranolol in man.Br. J. Clin. Pharmacol. 4:135–140 (1977).PubMedCentralPubMedGoogle Scholar
  26. 26g.
    R. Gomeni, G. Bianchetti, R. Sega, and P. L. Morselli. Pharmacokinetics of propranolol in normal healthy volunteers.J. Pharmacokin. Biopharm. 5:182–192 (1977).Google Scholar
  27. 27g.
    T. Ishizaki and K. Tawara. Comparison of disposition and effect of timolol and propranolol on exercise tachycardia.Eur. J. Clin. Pharmacol. 14:7–14 (1978).PubMedGoogle Scholar
  28. 28g.
    P. Jatlow, W. Bush, and H. Hochster. Improved liquid-chromatographic determination of propranolol in plasma, with fluorescence detection.Clin. Chem. 25:777–779 (1979).PubMedGoogle Scholar
  29. 29g.
    B. Karlberg, D. Lundberg, and H. Aberg. Excretion of propranolol in human breast milk.Acta. Pharmacol. Toxicol. 34:222–224 (1974).Google Scholar
  30. 30g.
    R. E. Kates. Absorption kinetics of sublingually administered propranolol.J. Med. 8:393–402 (1977).PubMedGoogle Scholar
  31. 31g.
    K. Kawashima, A. Levy, and S. Spector. Stereospecific radioimmunoassay for propranolol isomers.J. Pharmacol. Exp. Ther. 196:517–523 (1976).PubMedGoogle Scholar
  32. 32g.
    J. G. Kelly and D. G. McDevitt. Plasma protein binding of propranolol and isoprenaline in hyperthyroidism and hypothyroidism.Br. J. Clin. Pharmacol. 6:123–127 (1978).PubMedCentralPubMedGoogle Scholar
  33. 33g.
    D. M. Kornhauser, A. J. J. Wood, R. E. Vestal, R. A. Wilkinson, R. A. Branch, and D. G. Shand. Biological determinants of propranolol disposition in man.Clin. Pharmacol. Ther. 25:165–174 (1978).Google Scholar
  34. 34g.
    G. M. London, M. E. Safar, Y. Weiss, and P. L. Milliez. Isoproterenol sensitivity and total body clearance of propranolol in hypertensive patients.J. Clin. Pharmacol. 16:174–182 (1976).PubMedGoogle Scholar
  35. 35g.
    D. T. Lowenthal, W. A. Briggs, T. P. Gibson, H. Nelson, and W. J. Cirksena. Pharmacokinetics of oral propranolol in chronic renal disease.Clin. Pharmacol. Ther. 16:761–769 (1974).PubMedGoogle Scholar
  36. 36g.
    J. J. MacKichan, D. R. Pyszczynski, and W. J. Jusko. Analysis and disposition of low dose oral propranolol.Res. Comm. Chem. Pathol. Pharm. 20:531–538 (1978).Google Scholar
  37. 37g.
    J. McAinsh, N. S. Baber, R. Smith, and J. Young. Pharmacokinetic and pharmacodynamic studies with long-acting propranolol.Br. J. Pharmacol. 6:115–121 (1978).Google Scholar
  38. 38g.
    R. G. McAllister. Intravenous propranolol administration: a method for rapidly achieving and sustaining desired plasma levels.Clin. Pharmacol. Ther. 20:517–523 (1976).PubMedGoogle Scholar
  39. 39g.
    D. G. McDevitt, M. Frisk-Holmberg, J. W. Hollifleld, and D. G. Shand. Plasma binding and the affinity of propranolol for a beta receptor in man.Clin. Pharmacol. Ther. 20:152–157 (1976).PubMedGoogle Scholar
  40. 40g.
    A. Melander, K. Danielson, B. Schersten, and E. Wahlin. Enhancement of the bioavailability of propranolol and metoprolol by food.Clin. Pharmacol. Ther. 22:108–112 (1977).PubMedGoogle Scholar
  41. 41g.
    R. L. Nation, G. W. Peng, and W. L. Chiou. High-pressure liquid Chromatographic method for the simultaneous quantitative analysis of propranolol and 4-hydroxypropranolol in plasma.J. Chromatogr. 145:429–436 (1978).PubMedGoogle Scholar
  42. 42g.
    G. Nygard, W. H. Shelver, and S. K. Wahba Khalil. Sensitive high-pressure liquid Chromatographic determination of propranolol in plasma.J. Pharmaceut. Sci. 68:379–380 (1979).Google Scholar
  43. 43g.
    L. Offerhaus and J. R. van der Vecht. Improved fluorimetric assay of plasma propranolol.Br. J. Pharmacol. 3:1061–1062 (1976).Google Scholar
  44. 44g.
    R. L. Parsons. Plasma levels of propranolol in treated patients with coeliac disease and patients with Crohn's disease.Br. Med. J. 2:794–795 (1976).Google Scholar
  45. 45g.
    R. L. Parsons, C. M. Kaye, K. Raymond, J. R. Trounce, and P. Turner. Absorption of propranolol and practolol in coeliac disease.Gut 17:139–143 (1976).PubMedCentralPubMedGoogle Scholar
  46. 46g.
    J. W. Paterson, M. E. Conolly, and C. T. Dollery. The pharmacodynamics and metabolism of propranolol in man.Pharmacol. Clin. 2:127–133 (1970).Google Scholar
  47. 47g.
    K. M. Piafsky, O. Borga, I. Odar-Cederlof, C. Johansson, and F. Sjoqvist. Increased plasma protein binding of propranolol and chlorpromazine mediated by disease-induced elevations of plasma acid glycoprotein.N. Engl. J. Med. 299:1435–1438 (1978).PubMedGoogle Scholar
  48. 48g.
    M. Pine, L. Favrot, S. Smith, K. McDonald, and C. A. Chidsey. Correlation of plasma propranolol concentration with therapeutic response in patients with angina pectoris.Circulation 52:886–893 (1975).PubMedGoogle Scholar
  49. 49g.
    J. F. Pritchard, D. W. Schneck, W. J. Facz, and A. H. Hayes, Jr. The contribution of propranolol metabolites to the fluorometric assay of propranolol in human plasma.Clin. Biochem. 11:121–125 (1978).PubMedGoogle Scholar
  50. 50g.
    S. Rubenfeld, V. E. Silverman, K. M. A. Welch, L. E. Mallette, and P. O. Kohler. Variable plasma propranolol levels in thyrotoxicosis. Med. Intelligence300:353–354 (1979).Google Scholar
  51. 51g.
    D. G. Shand and R. E. Rangno. The disposition of propranolol. I. Elimination during oral absorption in man.Pharmacol. 7:159–168 (1972).Google Scholar
  52. 52g.
    E. A. Sotaniemi, M. Anttila, R. O. Pelkonen, P. Jarvensivu, and H. Sundquist. Plasma clearance of propranolol and sotalol and hepatic drug-metabolizing enzyme activity.Clin. Pharmacol. Ther. 26:153–161 (1979).PubMedGoogle Scholar
  53. 53g.
    A. M. Taburet, A. A. Taylor, J. R. Mitchell, D. E. Rollins, and J. L. Pool. Plasma concentrations of propranolol and 4-hydroxypropranolol in man measured by high pressure liquid chromatography.Life Sci. 24:209–218 (1979).PubMedGoogle Scholar
  54. 54g.
    E. A. Taylor, T. L. Kaspi, and P. Turner. The pH dependent absorption of propranolol and indomethacin by parafilm, a stimulant of salivary secretion.J. Pharm. Pharmacol. 30:813–814 (1978).PubMedGoogle Scholar
  55. 55g.
    F. D. Thompson, A. M. Joekes, and D. M. Foulkes. Pharmacodynamics of propranolol in renal failure.Br. Med. J. 2:434–436 (1972).PubMedCentralPubMedGoogle Scholar
  56. 56g.
    J. Vasiliades, T. Turner, and C. Owens. A modified sensitive spectrofluorometric method for the determination of propranolol in serum.Am. J. Clin. Pathol. 70:793–799 (1977).Google Scholar
  57. 57g.
    R. E. Vestal, D. M. Kornhauser, J. W. Hollifield, and D. G. Shand. Inhibition of propranolol metabolism by chlorpromazine.Clin. Pharmacol. Ther. 25:19–24 (1979).PubMedGoogle Scholar
  58. 58g.
    R. E. Vestal, A. J. J. Wood, R. A. Branch, D. G. Shand, and G. R. Wilkinson. Effects of age and cigarette smoking on propranolol disposition.Clin. Pharmacol. Ther. 26:8–15 (1979).PubMedGoogle Scholar
  59. 59g.
    R. E. Vestal, A. J. J. Wood, and D. G. Shand. Reduced beta-adrenoceptor sensitivity in the elderly.Clin. Pharmacol. Ther. 26:181–186 (1979).PubMedGoogle Scholar
  60. 60g.
    T. Walle, E. C. Conradi, U. K. Walle, T. C. Fagan, and T. E. Gaffney. The predictable relationship between plasma levels and dose during chronic propranolol therapy.Clin. Pharmacol. Ther. 24:668–677 (1978).PubMedGoogle Scholar
  61. 61g.
    T. Walle, T. C. Fagan, E. C. Conradi, U. K. Walle, and T. E. Gaffney. Presystemic and systemic glucuronidation of propranolol.Clin. Pharmacol. Ther. 26:167–172 (1979).PubMedGoogle Scholar
  62. 62g.
    Y. A. Weiss, M. E. Safar, C. Chevillard, A. Frydman, A. Simon, P. Lemaire, and J. M. Alexandre. Comparison of the pharmacokinetics of intravenous dl-propranolol in borderline and permanent hypertension.Eur. J. Clin. Pharmacol. 10:387–393 (1976).PubMedGoogle Scholar
  63. 63g.
    A. J. J. Wood, K. Carr, R. E. Vestal, S. Belcher, G. R. Wilkinson, and D. G. Shand. Direct measurement of propranolol bioavailability during accumulation to steady-state.Br. J. Clin. Pharmacol. 6:345–350 (1978).PubMedCentralPubMedGoogle Scholar
  64. 64g.
    A. J. J. Wood, D. M. Kornhauser, G. R. Wilkinson, D. G. Shand, and R. A. Branch. The influence of cirrhosis on steady-state blood concentrations of unbound propranolol after oral administration.Clin. Pharmacokin. 3:478–487 (1978).Google Scholar
  65. 65g.
    M. Wood, D. G. Shand, and A. J. J. Wood. Altered drug binding due to the use of indwelling heparinized cannulas (heparin lock) for sampling.Clin. Pharmacol. Ther. 25:103–107 (1979).PubMedGoogle Scholar
  66. 66g.
    R. Zacest and J. Koch-Weser. Relation of propranolol plasma level to beta-blockade during oral therapy. Pharmacol.7:178–184 (1972).Google Scholar

Propranolol: additional references

  1. 67g.
    W. H. Aellig. Beta-adrenoceptor blocking activity and duration of action of pindolol and propranolol in healthy volunteers.Br. J. Clin. Pharmacol. 3:251–257 (1976).PubMedCentralPubMedGoogle Scholar
  2. 68g.
    R. A. Branch and D. G. Shand. Propranolol disposition in chronic liver disease: a physiological approach.Clin. Pharmacokin. 1:264–279 (1976).Google Scholar
  3. 69g.
    M. F. Cuthbert and R. F. Collins. Plasma levels and beta adrenoceptor blockade with acebutolol, practolol and propranolol in man.Br. J. Clin. Pharmacol. 2:49–55 (1975).PubMedCentralPubMedGoogle Scholar
  4. 70g.
    J. F. DePlaen, A. Amery, and T. Reybrouck. Comparative potency of atenolol and propranolol as beta-adrenergic blocking agents in man.Eur. J. Clin. Pharmacol. 10:297–303 (1976).Google Scholar
  5. 71g.
    C. F. George, T. Fenyvesi, M. E. Conolly, and C. T. Dollery. Pharmacokinetics of dextro-laevo- and racemic propranolol in man.Eur. J. Clin. Pharmacol. 4:74–76 (1972).PubMedGoogle Scholar
  6. 72g.
    C. F. George, M. L. Orme, P. Buranapong, D. Macerlean, A. M. Breckenridge, and C. T. Dollery. Contribution of the liver to overall elimination of propranolol.J. Pharmacokin. Biopharm. 4:17–27 (1976).Google Scholar
  7. 73g.
    M. Guazzi, C. Fiorentini, A. Polese, M. T. Olivari, and F. Magrini. Antihypertensive action of propranolol in man: lack of evidence for a neural depressive effect.Clin. Pharmacol. Ther. 20:304–309 (1976).PubMedGoogle Scholar
  8. 74g.
    D. J. Hetherington, M. B. Comerford, G. Nyberg, and M. M. Besterman. Comparison of two adrenergic beta-receptor blocking agents, alprenolol and propranolol, in treatment of angina pectoris.Br. Heart J. 35:320–333 (1973).Google Scholar
  9. 75g.
    D. C. Hicks, A. G. Arbab, P. Turner, and M. Hills. A comparison of intravenous pindolol and propranolol in normal man.J. Clin. Pharmacol. 12:212–216 (1972).Google Scholar
  10. 76g.
    B. Holland and N. M. Kaplan. Propranolol in the treatment of hypertension.N. Engl. J. Med. 294:930–935 (1976).PubMedGoogle Scholar
  11. 77g.
    J. W. Hollifield, K. Sherman, R. V. Zwagg, and D. G. Shand. Proposed mechanisms of propranolol's antihypertensive effect in essential hypertension.N. Engl. J. Med. 294:68–73 (1976).Google Scholar
  12. 78g.
    J. Kanto, T. Kleimola, R. Mantyla, and E. Syvalahti. Pharmacological effect of propranolol after a single oral dose.Acta. Pharmacol. Toxicol. 39:573–576 (1976).Google Scholar
  13. 79g.
    B. E. Karlberg, B. Kagedal, L. Tegler, and K. Tolagen. Renin concentrations and effects of propranolol and spironolactone in patients with hypertension.Br. Med. J. 1:251–254 (1976).PubMedCentralPubMedGoogle Scholar
  14. 80g.
    R. E. Kates. Absorption kinetics of sublingually administered propranolol.J. Med. 8:393–402 (1977).PubMedGoogle Scholar
  15. 81g.
    J. Koch-Weser. Serum drug concentrations as therapeutic guides.N. Engl. J. Med. 287:227–231 (1972).PubMedGoogle Scholar
  16. 82g.
    R. D. Kulkarni, L. M. DaSilva, N. L. Chabria, and D. R. Chadha. Beta-2 adrenoceptor blocking activity of penbutolol and propranolol at very low doses.Clin. Pharmacol. Ther. 21:685–690 (1976).Google Scholar
  17. 83g.
    M. M. LeWinter, M. H. Crawford, J. S. Karliner, and R. A. O'Rourke. Effects of oral propranolol in normal subjects.Clin. Pharmacol. Ther. 17:709–712 (1975).PubMedGoogle Scholar
  18. 84g.
    D. T. Lowenthal. Pharmacokinetics of propranolol, quinidine, procainamide and lidocaine in chronic renal disease.Am. J. Med. 62:532–538 (1977).PubMedGoogle Scholar
  19. 85g.
    D. G. McDevitt and D. G. Shand. Plasma concentrations and the time-course of beta blockade due to propranolol.Clin. Pharmacol. Ther. 18:708–713 (1975).PubMedGoogle Scholar
  20. 86g.
    C. E. McLean and B. C. Deane. Propranolol dose determinants including blood level studies.Angiology 21:536–545 (1970).PubMedGoogle Scholar
  21. 87g.
    R. J. McMurtry. Propranolol, hypoglycemia and hypertensive crisis.Ann. Intern. Med. 80:669–670 (1974).PubMedGoogle Scholar
  22. 88g.
    R. R. Miller, H. G. Olson, E. A. Amsterdam, and D. T. Mason. Propranolol withdrawal rebound phenomenon.N. Engl. J. Med. 293:416–418 (1975).PubMedGoogle Scholar
  23. 89g.
    G. W. Molnar and R. C. Read. Propranolol enhancement of hypoglycemic sweating.Clin. Pharmacol. Ther. 15:490–496 (1973).Google Scholar
  24. 90g.
    A. S. Nies, G. H. Evans, and D. G. Shand. The hemodynamic effects of beta adrenergic blockade on the flow-dependent hepatic clearance of propranolol.J. Pharmacol. Exp. Ther. 184:716–720 (1973).PubMedGoogle Scholar
  25. 91g.
    K. O'Malley, B. Basuray, and J. L. McNay. Dissociation of the time courses of decay of propranolol from plasma and cardiovascular effects after chronic dosing.Br. J. Clin. Pharmacol. 3:347–348 (1975).Google Scholar
  26. 92g.
    D. G. Shand. Pharmacokinetic properties of the beta-adrenergic receptor blocking drugs,Drugs 7:39–47 (1974).PubMedGoogle Scholar
  27. 93g.
    D. G. Shand. Drug Therapy: Propranolol.N. Engl. J. Med. 293:280–285 (1975).PubMedGoogle Scholar
  28. 94g.
    E. Vervloet, M. Pluym, J. Cilissen, K. Kohlen, and F. W. H. M. Merkus. Propranolol serum levels during twenty-four hours.Clin. Pharmacol. Ther. 22:853–857 (1977).PubMedGoogle Scholar
  29. 95g.
    G. F. Winkler and R. R. Young. Efficacy of chronic propranolol therapy in action tremors of the familial, senile or essential varieties.N. Engl. J. Med. 290:984–988 (1974).PubMedGoogle Scholar


  1. 1h.
    L. B. Sheiner and T. N. Tozer. Clinical Pharmacokinetics—the Use of Plasma Concentrations of Drugs. In K. L. Melmon and H. F. Morrelli (eds.),Clinical Pharmacology, 2nd ed. MacMillan, New York, 1978, pp. 71–109.Google Scholar
  2. 2h.
    M. Rowland and T. N. Tozer.Clinical Pharmacokinetics: Concepts and Applications. Lea & Febiger, Philadelphia, 1980.Google Scholar
  3. 3h.
    G. S. Avery (ed.).Clinical Pharmacokinetics. ADIS Press, Auckland, New Zealand, Vols. 1–5, 1976–1980.Google Scholar
  4. 4h.
    L. Z. Benet and R. L. Galeazzi. Noncompartmental determination of the steady-state volume of distribution.J. Pharm. Sci. 68:1071–1074 (1979).PubMedGoogle Scholar
  5. 5h.
    G. R. Wilkinson and D. G. Shand. A physiological approach to hepatic drug clearance.Clin. Pharmacol. Ther. 18:377–390 (1975).PubMedGoogle Scholar
  6. 6h.
    J. G. Wagner. Kinetics of pharmacological response.J. Theor. Biol. 20:173–201 (1968).PubMedGoogle Scholar
  7. 7h.
    L. B. Sheiner, D. R. Stanski, S. Vozeh, R. D. Miller, and J. Ham. Simultaneous modelling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine.Clin. Pharmacol. Ther. 25:358–371 (1979).PubMedGoogle Scholar
  8. 8h.
    M. Rowland and G. Tucker. Symbols in pharmacokinetics.J. Pharmacokin. Biopharm. 8:497–507 (1980).Google Scholar

Copyright information

© Plenum Publishing Corporation 1981

Authors and Affiliations

  • Lewis B. Sheiner
    • 1
  • Leslie Z. Benet
    • 2
  • Louis A. Pagliaro
    • 3
  1. 1.Departments of Laboratory Medicine and MedicineUniversity of CaliforniaSan Francisco
  2. 2.Department of Pharmacy, School of PharmacyUniversity of CaliforniaSan Francisco
  3. 3.Faculty of PharmacyUniversity of AlbertaAlbertaCanada

Personalised recommendations