Pharmacokinetic evaluation of hemodialysis in acute drug overdose

  • S. Takki
  • J. G. Gambertoglio
  • D. H. Honda
  • T. N. Tozer
Pharmacokinetic Data
First Online:
Received:
Revised:

Abstract

The contribution of hemodialysis to the removal of drugs in the overdosed patient continues to be questioned. Often the value of hemodialysis is judged on qualitative rather than quantitative information. The latter information can be obtained by applying pharmacokinetic principles. The primary pharmacokinetic parameters required to evaluate drug removal by hemodialysis are (1) apparent volume of distribution, (2) dialysis clearance, and (3) total body clearance. Eighteen drugs commonly encountered in the overdose setting are evaluated using this approach.

Key words

drug overdose hemodialysis pharmacokinetic evaluation dialyzability 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    P. D. Doolan, W. P. Walsh, L. H. Kyle, and H. Wishinsky. Acetylsalicylic acid intoxication: A proposed method of treatment.J. Am. Med. Assoc. 146:105–106 (1951).PubMedCrossRefGoogle Scholar
  2. 2.
    R. J. Anderson, J. G. Gambertoglio, and R. W. Schrier.Clinical Use of Drugs in Renal Failure, Charles C Thomas, Springfield, Ill., 1976.Google Scholar
  3. 3.
    S. Locket. Hemodialysis in the treatment of acute poisoning.Proc. Roy. Soc. Med. 63:427–430 (1970).PubMedCentralPubMedGoogle Scholar
  4. 4.
    J. G. Knepshield, G. E. Schreiner, D. T. Lowenthal, and M. D. Gelfand. Dialysis of poisons and drugs—Annual review.Trans. Am. Soc. Art. Int. Org. 19:590–633 (1973).CrossRefGoogle Scholar
  5. 5.
    C. Clemmesen and E. Nilsson. Therapeutic trends in the treatment of barbiturate poisoning: The Scandinavian method.Clin. Pharmacol. Ther. 2:220–229 (1961).PubMedGoogle Scholar
  6. 6.
    C. Clemmesen. Treatment of narcotic intoxication: Results and principles of the “Scandinavian” method especially concerning stimulation.Danish Med. Bull. 10:97–99 (1963).PubMedGoogle Scholar
  7. 7.
    H. Matthew. Acute poisoning: Some myths and misconceptions.Br. Med. J. 1:519–522 (1971).PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    J. P. Merrill. Treatment of drug intoxication by hemoperfusion.New Engl. J. Med. 284:911–912 (1971).PubMedCrossRefGoogle Scholar
  9. 9.
    J. M. Rosin. Resin hemoperfusion. Letter to the editor.New Engl. J. Med. 285:123 (1971).Google Scholar
  10. 10.
    A. R. Hansen, K. A. Kennedy, J. J. Ambre, and L. J. Fischer. Giutethimide poisoning. A metabolite contributes to morbidity and mortality.New Engl. J. Med. 292:250–252 (1975).PubMedCrossRefGoogle Scholar
  11. 11.
    G. L. Ackerman, J. E. Doherty, and W. J. Flanigan. Peritoneal dialysis and hemodialysis of tritiated digoxin.Ann. Intern. Med. 67:718–723 (1967).PubMedCrossRefGoogle Scholar
  12. 12.
    E. Iisalo and J. Forsström. Elimination of digoxin during maintenance haemodialysis.Ann. Clin. Res. 6:203–206 (1974).PubMedGoogle Scholar
  13. 13.
    E. Iisalo. Clinical pharmacokinetics of digoxin.Clin. Pharmacokin. 2:1–16 (1977).CrossRefGoogle Scholar
  14. 14.
    J. E. Doherty, J. K. Bissett, J. J. Kane, N. de Souza, M. L. Murphy, W. J. Flanigan, and G. V. Dalrymple. Tritiated digoxin: Studies in renal disease in human subjects.Int. J. Clin. Pharmacol. 12:89–95 (1975).Google Scholar
  15. 15.
    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).CrossRefGoogle Scholar
  16. 16.
    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
  17. 17.
    U. Klotz. Pathophysiological and disease-induced changes in drug distribution volume: Pharmacokinetic implications.Clin. Pharmacokin. 1:204–218 (1976).CrossRefGoogle Scholar
  18. 18.
    J. B. Hawkins and P. R. Dorken. Letter to the editor.Lancet 1:839–840 (1969).PubMedGoogle Scholar
  19. 19.
    J. M. Davis and W. E. Fann. Lithium.Ann. Rev. Pharmacol. 11:285–302 (1971).PubMedCrossRefGoogle Scholar
  20. 20.
    V. Groth, W. Prellwitz, and E. Janchen. Estimation of pharmacokinetic parameters of lithium from saliva and urine.Clin. Pharmacol. Ther. 16:490–498 (1974).PubMedGoogle Scholar
  21. 21.
    A. Amdisen and H. Skjoldborg. Hemodialysis for lithium poisoning.Lancet 2:213 (1969).PubMedCrossRefGoogle Scholar
  22. 22.
    L. B. Berman, H. J. Jeghers, G. E. Schreiner, and A. J. Pallotta. Hemodialysis, an effective therapy for acute barbiturate poisoning.J. Am. Med. Assoc. 161:820–827 (1956).PubMedCrossRefGoogle Scholar
  23. 23.
    P. Lous. Plasma levels and urinary excretion of three barbituric acids after oral administration to man.Acta Pharmacol. Toxicol. 10:147–165 (1954).CrossRefGoogle Scholar
  24. 24.
    P. Lous. Blood serum and cerebrospinal fluid levels and renal clearance of phenemal in treated epileptics.Acta Pharmacol. Toxicol. 10:166–177 (1954).CrossRefGoogle Scholar
  25. 25.
    O. Svensmark and F. Buchthal. Accumulation of phenobarbital in man.Epilepsia 4:199–206 (1963).PubMedCrossRefGoogle Scholar
  26. 26.
    W. J. Waddell and T. C. Butler. The distribution and excretion of phenobarbital.J. Clin. Invest. 36:1217–1226 (1957).PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    L. W. Henderson and J. P. Merrill. Treatment of barbiturate intoxication with a report of recent experience at Peter Bent Hospital.Ann. Intern. Med. 64:876–891 (1966).PubMedCrossRefGoogle Scholar
  28. 28.
    T. N. Tozer, L. D. Witt, L. Gee, T. Tong, and J. Gambertoglio. Evaluation of hemodialysis for ethchlorvynol (Placidyl) overdose.Am. J. Hosp. Pharm. 31:986–989 (1974).PubMedGoogle Scholar
  29. 29.
    P. F. Gibson and N. Wright. Ethchlorvynol in biological fluids: Specificity of assay methods.J. Pharm. Sci. 61:169–171 (1972).PubMedCrossRefGoogle Scholar
  30. 30.
    L. T. Welch, J. D. Bower, C. E. Ott, and A. S. Hume. Oil dialysis for ethchlorvynol intoxication.Clin. Pharmacol. Ther. 13:745–749 (1972).PubMedGoogle Scholar
  31. 31.
    D. S. Adler, E. Martin, J. G. Gambertoglio, T. N. Tozer, and J. P. Spire. Hemodialysis of phenytoin in a uremic patient.Clin. Pharmacol. Ther. 18:65–69 (1975).PubMedGoogle Scholar
  32. 32.
    E. Martin, J. G. Gambertoglio, D. S. Adler, T. N. Tozer, L. A. Roman, and H. Grausz. Removal of phenytoin by hemodialysis in uremic patients.J. Am. Med. Assoc. 238:1750–1753 (1977).CrossRefGoogle Scholar
  33. 33.
    E. Martin, T. N. Tozer, L. Sheiner, and S. Riegelman. Clinical pharmacokinetics of phenytoin.J. Pharmacokin. Biopharm. 5:579–596 (1977).CrossRefGoogle Scholar
  34. 34.
    A. J. Glazko, T. Chang, J. Baukema, W. A. Dill, J. R. Goulet, and R. A. Buchanan. Metabolic disposition of diphenylhydantoin in normal human subjects following intravenous administration.Clin. Pharmacol. Ther. 10:498–504 (1969).PubMedGoogle Scholar
  35. 35.
    K. Arnold and N. Gerber. The rate of decline of diphenyldantoin in human plasma.Clin. Pharmacol. Ther. 11:121–134 (1970).PubMedGoogle Scholar
  36. 36.
    I. Odar-Cederlöf and O. Borgå. Kinetics of diphenylhydantoin in uraemic patients: Consequences of decreased plasma protein binding.Eur. J. Clin. Pharmacol. 7:31–37 (1974).PubMedCrossRefGoogle Scholar
  37. 37.
    F. Bochner, W. D. Hooper, J. M. Sutherland, J. J. Eadie, and J. H. Tyrer. The renal handling of diphenylhydantoin and 5-(hydroxyphenyl)-5-phenylhydantoin.Clin. Pharmacol. Ther. 14:791–796 (1973).PubMedGoogle Scholar
  38. 38.
    W. D. Hooper, F. Bochner, M. J. Eadie, and J. H. Tyrer. Plasma protein binding of diphenylhydantoin: Effects of sex hormones, renal and hepatic disease.Clin. Pharmacol. Ther. 15:276–288 (1974).PubMedGoogle Scholar
  39. 39.
    T. M. Ludden, J. P. Allen, W. A. Valutsky, A. V. Vicuna, J. M. Nappi, S. F. Hoffman, J. E. Wallace, D. Lalka, and J. L. McNay. Individualization of phenytoin dosage regimens.Clin. Pharmacol. Ther. 21:287–293 (1977).PubMedGoogle Scholar
  40. 40.
    N. Spritz, T. J. Fahey, D. D. Thompson, and A. L. Rubin. The use of extracorporeal hemodialysis in the treatment of salicylate intoxication in a 2-year-old child.Pediatrics 24:540–543 (1959).PubMedGoogle Scholar
  41. 41.
    R. J. Kallen, S. Zaltzman, F. L. Coe, and J. Metcoff. Hemodialysis in children: Technique, kinetic aspects related to varying body size and application to salicylate intoxication, acute renal failure and some other disorders.Medicine 45:1–50 (1966).PubMedCrossRefGoogle Scholar
  42. 42.
    A. K. Done. Salicylate intoxication: Significance of measurement of salicylate in blood in cases of acute ingestion.Pediatrics 26:800–807 (1960).PubMedGoogle Scholar
  43. 43.
    S. Riegelman, J. Loo, and M. Rowland. Concept of a volume of distribution and possible errors in evaluation of this parameter.J. Pharm. Sci. 57:128–133 (1968).PubMedCrossRefGoogle Scholar
  44. 44.
    M. Rowland and S. Riegelman. Pharmacokinetics of acetylsalicylic acid and salicylic acid after intravenous administration in man.J. Pharm. Sci. 57:1313–1319 (1968).CrossRefGoogle Scholar
  45. 45.
    G. Levy. Pharmacokinetics of salicylate elimination in man.J. Pharm. Sci. 54:959–967 (1965).PubMedCrossRefGoogle Scholar
  46. 46.
    T. Tsuchiya and G. Levy. Biotransformation of salicylic acid to its acyl and phenolic glucuronides in man.J. Pharm. Sci. 61:800–801 (1972).PubMedCrossRefGoogle Scholar
  47. 47.
    O. Borgå, I. Odar-Cederlöf, V. Ringberger, and A. Norlin. Protein binding of salicylate in uremic and normal plasma.Clin. Pharmacol. Ther. 20:464–475 (1976).PubMedGoogle Scholar
  48. 48.
    N. R. Farid, J. P. Glynn, and D. N. S. Kerr. Hemodialysis in paracetamol poisoning.Lancet 2:396–398 (1972).PubMedCrossRefGoogle Scholar
  49. 49.
    S. Øie, D. T. Lowenthal, W. A. Briggs, and G. Levy. Effect of hemodialysis on kinetics of acetaminophen elimination by anephric patients.Clin. Pharmacol. Ther. 18:680–686 (1975).PubMedGoogle Scholar
  50. 50.
    L. F. Prescott, P. Roscoe, N. Wright, and S. S. Brown. Plasma-paracetamol half-life and hepatic necrosis in patients with paracetamol overdose.Lancet 1:519–522 (1971).PubMedCrossRefGoogle Scholar
  51. 51.
    L. F. Prescott and N. Wright. The effects of hepatic and renal damage on paracetamol metabolism and excretion following overdosage: A pharmacokinetic study.Br. J. Pharmacol. 49:602–613 (1973).PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    G. Levy and H. Yamada. Drug biotransformation interactions in man. III. Acetaminophen and salicylamide.J. Pharm. Sci. 60:215–221 (1971).PubMedCrossRefGoogle Scholar
  53. 53.
    K. S. Albert, A. J. Sedman, P. Wilkinson, R. G. Stoll, W. J. Murray, and J. G. Wagner. Bioavailability studies of acetaminophen and nitrofurantoin.J. Clin. Pharmacol. 14:264–279 (1974).PubMedCrossRefGoogle Scholar
  54. 54.
    N. E. Stalker, J. G. Gambertoglio, C. J. Fukumitsu, J. L. Naughton, and L. Z. Benet. Acute massive chloral hydrate intoxication treated with hemodialysis: A clinical pharmacokinetic analysis.J. Clin. Pharmacol. 18:136–142 (1978).PubMedCrossRefGoogle Scholar
  55. 55.
    N. D. Vaziri, K. P. Kumar, K. Mirahmadi, and S. M. Rosen. Hemodialysis in treatment of acute chloral hydrate poisoning.Southern Med. J. 70:377–378 (1977).PubMedCrossRefGoogle Scholar
  56. 56.
    E. M. Sellers, M. Lang, J. Koch-Weser, E. Leblanc, and H. Kalant. Interaction of chloral hydrate and ethanol in man. I. Metabolism.Clin. Pharmacol. Ther. 13:37–49 (1972).PubMedGoogle Scholar
  57. 57.
    D. D. Breimer. Clinical pharmacokinetics of hypnotics.Clin. Pharmacokin. 2:93–109 (1977).CrossRefGoogle Scholar
  58. 58.
    E. K. Marshall and A. H. Owens. Absorption, excretion and metabolic fate of chloral hydrate and trichloroethanol.Johns Hopkins Hosp. Bull. 95:1–18 (1954).Google Scholar
  59. 59.
    I. A. Cruz, N. C. Cramer, and A. E. Parrish. Hemodialysis in chlordiazepoxide toxicity.J. Am. Med. Assoc. 202:438–440 (1967).CrossRefGoogle Scholar
  60. 60.
    M. A. Schwartz, E. Postma, and Z. Gaut. Biological half-life of chlordiazepoxide and its metabolite demoxepam in man.J. Pharm. Sci. 60:1500–1503 (1971).PubMedCrossRefGoogle Scholar
  61. 61.
    B. A. Koechlin, M. A. Schwartz, G. Krol, and W. Oberhausli. The metabolic fate of C14 labeled chlordiazepoxide in man, in the dog and in the rat.J. Pharmacol. Exp. Ther. 148:399–411 (1965).PubMedGoogle Scholar
  62. 62.
    E. van der Kleijn. Protein binding and lipophilic nature of ataractics of the meprobamate and diazepine group.Arch. Int. Pharmacodyn. Ther. 179:225–250 (1969).PubMedGoogle Scholar
  63. 63.
    J. D. Maxwell, M. Carrella, J. D. Parkes, R. Williams, G. P. Mould, and S. H. Curry. Plasma disappearance and cerebral effects of chlorpromazine in cirrhosis.Clin. Sci. 43:143–151 (1972).PubMedGoogle Scholar
  64. 64.
    S. H. Curry, J. M. Davis, D. S. Janowsky, and J. H. L. Marshall. Factors affecting chlorpromazine plasma levels in psychiatric patients.Arch. Gen. Psychol. 22:209–215 (1970).CrossRefGoogle Scholar
  65. 65.
    M. M. Avram and J. T. McGinn. Extracorporeal hemodialysis in phenothiazine overdosage.J. Am. Med. Assoc. 197:142–143 (1966).CrossRefGoogle Scholar
  66. 66.
    E. van der Kleijn, J. M. van Rossum, E. Muskens, and N. Rijntjes. Pharmacokinetics of diazepam in dogs, mice and humans.Acta Pharmacol. Toxicol. Suppl. 29:109–127 (1971).CrossRefGoogle Scholar
  67. 67.
    S. A. Kaplan, M. L. Jack, K. Alexander, and R. E. Weinfeld. Pharmacokinetic profile of diazepam in man following single intravenous and oral and chronic oral administrations.J. Pharm. Sci. 62:1789–1796 (1973).PubMedCrossRefGoogle Scholar
  68. 68.
    L. Hillestad, T. Hansen, and H. Melson. Diazepam metabolism in normal man.Clin. Pharmacol. Ther. 16:485–489 (1974).PubMedGoogle Scholar
  69. 69.
    B. F. Chandler, W. H. Meroney, W. W. Czarnecki, R. H. Herman, J. D. Cheitlin, L. R. Goldbaum, and E. G. Herndon. Artificial hemodialysis in management of glutethimide intoxication.J. Am. Med. Assoc. 170:914–917 (1959).PubMedCrossRefGoogle Scholar
  70. 70.
    J. F. Maher, G. E. Schreiner, and F. B. Westervelt. Acute glutethimide intoxication.Am. J. Med. 33:70–82 (1962).PubMedCrossRefGoogle Scholar
  71. 71.
    S. H. Curry, D. Riddall, J. S. Gordon, P. Simpson, T. B. Binns, R. K. Rondel, and C. McMartin. Disposition of glutethimide in man.Clin. Pharmacol. Ther. 12:849–857 (1971).PubMedGoogle Scholar
  72. 72.
    R. K. Maddock and H. A. Bloomer. Meprobamate overdosage: Evaluation of its severity and methods of treatment.J. Am. Med. Assoc. 201:999–1003 (1967).CrossRefGoogle Scholar
  73. 73.
    J. Graae and J. Hadefogea. Svaer meprobamat forgitftning behandlet med haemooq peritoneal dialyse.Nordisk Med. 81:601–603 (1969).Google Scholar
  74. 74.
    S. S. Walkenstein, C. M. Knebel, J. A. MacMullen, and J. Seifter. Distribution of meprobamate and its metabolites.J. Pharmacol. Exp. Ther. 123:254–258 (1958).PubMedGoogle Scholar
  75. 75.
    L. E. Hollister and G. Levy. Kinetics of meprobamate elimination in humans.Chemotherapia 9:20–24 (1964).CrossRefGoogle Scholar
  76. 76.
    A. T. Proudfoot, J. Noble, J. Nimmo, S. S. Brown, and J. C. Cameron. Peritoneal dialysis and hemodialysis in methaqualone (Mandrax) poisoning.Scot. Med. J. 13:232–236 (1968).Google Scholar
  77. 77.
    R. K. Nayak, R. D. Smyth, J. H. Chamberlain, A. Polk, A. F. De Long, T. Herczeg, P. B. Chemburkar, R. S. Joslin, and N. H. Reavey-Cantwell. Methaqualone pharmacokinetics after single- and multiple-dose administration in man.J. Phamacokin. Biopharm. 2:107–121 (1974).CrossRefGoogle Scholar
  78. 78.
    G. Alvin, O. Ericson, S. Levander, and J.-E. Lindgren. Plasma concentrations and effects of methaqualone after single and multiple oral doses in man.Eur. J. Clin. Pharmacol. 7:449–454 (1974).CrossRefGoogle Scholar
  79. 79.
    G. Xanthaky, A. W. Freireich, W. Matusiak, and L. Lukash. Hemodialysis in methyprylon poisoning.J. Am. Med. Assoc. 198:1212–1213 (1966).CrossRefGoogle Scholar
  80. 80.
    J. M. Mandelbaum and N. M. Simon. Severe methyprylon intoxication treated by hemodialysis.J. Am. Med. Assoc. 216:139–140 (1971).CrossRefGoogle Scholar
  81. 81.
    A. S. Pancorbo, P. A. Palagi, J. J. Piecoro, and H. D. Wilson. Hemodialysis in methyrylon overdose—Some pharmacokinetic considerations.J. Am. Med. Assoc. 237:470–471 (1977).CrossRefGoogle Scholar
  82. 82.
    N. Burnstein and H. K. Stauss. Attempted suicide with methyprylon.J. Am. Med. Assoc. 194:1139–1140 (1965).CrossRefGoogle Scholar
  83. 83.
    B. Alexanderson. Pharmacokinetics of nortriptyline in man after single and multiple oral doses: The predictability of steady-state plasma concentrations from single-dose plasmalevel data.Eur. J. Clin. Pharmacol. 4:82–91 (1972).PubMedCrossRefGoogle Scholar
  84. 84.
    B. Alexanderson. Pharmacokinetics of desmethylimipramine and nortriptyline in man after single and multiple oral doses—A cross over study.Eur. J. Clin. Pharmacol. 5:1–10 (1972).CrossRefGoogle Scholar
  85. 85.
    B. Alexanderson and O. Borgå. Urinary excretion of nortriptyline and five of its metabolites in man.Eur. J. Clin. Pharmacol. 5:174–180 (1973).CrossRefGoogle Scholar
  86. 86.
    O. Borgå, D. L. Azarnoff, G. P. Forshell, and F. Sjöqvist. Plasma protein binding of tricyclic antidepressants in man.Biochem. Pharmacol. 18:2135–2143 (1969).PubMedCrossRefGoogle Scholar
  87. 87.
    J. Rasmussen. Poisoning by amitriptyline, imipramine and nortriptyline.Danish Med. Bull. 13:201–203 (1966).PubMedGoogle Scholar
  88. 88.
    L. C. Mark. Pharmacokinetics of barbiturates. In H. Matthew (ed.),Acute Barbiturate Poisoning, Excerpta Medica, Amsterdam, 1971, p. 75.Google Scholar
  89. 89.
    J. G. Setter, R. B. Freeman, J. F. Maher, and G. E. Schreiner. Factors influencing the dialysis of barbiturates.Trans. Am. Soc. Art. Int. Org. 10:340–344 (1964).Google Scholar
  90. 90.
    N. E. Gary, J. F. Maher, M. H. De Myttenacre, S. H. Liggero, K. G. Scott, W. Matusiak, and G. E. Schreiner. Acute propoxyphene hydrochloride intoxication.Arch. Intern. Med. 121:453–457 (1968).PubMedCrossRefGoogle Scholar
  91. 91.
    K. Verebely and E. C. Inturrisi. Disposition of propoxyphene and norpropoxyphene in man after a single dose.Clin. Pharmacol Ther. 15:302–309 (1974).PubMedGoogle Scholar
  92. 92.
    R. L. Wolen, E. A. Ziege, and C. M. Gruber. Determination of propoxyphene and norpropoxyphene by chemical ionization mass fragmentography.Clin. Pharmacol. Ther. 17:15–20 (1975).PubMedGoogle Scholar
  93. 93.
    S. M. Mauer, C. L. Paxson, B. von Hartizsch, T. J. Buselmeier, and C. M. Kjellstrand. Hemodialysis in an infant with propoxyphene intoxication.Clin. Pharmacol. Ther. 17:88–92 (1975).PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1978

Authors and Affiliations

  • S. Takki
    • 1
  • J. G. Gambertoglio
    • 2
  • D. H. Honda
    • 2
  • T. N. Tozer
    • 3
  1. 1.Division of Clinical Pharmacology, Department of Medicine, School of MedicineUniversity of CaliforniaSan Francisco
  2. 2.Division of Clinical Pharmacy, Department of Pharmacy, School of PharmacyUniversity of CaliforniaSan Francisco
  3. 3.Department of Pharmacy, School of PharmacyUniversity of CaliforniaSan Francisco

Personalised recommendations