Skip to main content
Log in

Pharmacokinetic evaluation of hemodialysis in acute drug overdose

  • Published:
Journal of Pharmacokinetics and Biopharmaceutics Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  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).

    Article  CAS  PubMed  Google Scholar 

  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. S. Locket. Hemodialysis in the treatment of acute poisoning.Proc. Roy. Soc. Med. 63:427–430 (1970).

    CAS  PubMed Central  PubMed  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  5. C. Clemmesen and E. Nilsson. Therapeutic trends in the treatment of barbiturate poisoning: The Scandinavian method.Clin. Pharmacol. Ther. 2:220–229 (1961).

    CAS  PubMed  Google Scholar 

  6. C. Clemmesen. Treatment of narcotic intoxication: Results and principles of the “Scandinavian” method especially concerning stimulation.Danish Med. Bull. 10:97–99 (1963).

    CAS  PubMed  Google Scholar 

  7. H. Matthew. Acute poisoning: Some myths and misconceptions.Br. Med. J. 1:519–522 (1971).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. J. P. Merrill. Treatment of drug intoxication by hemoperfusion.New Engl. J. Med. 284:911–912 (1971).

    Article  CAS  PubMed  Google Scholar 

  9. J. M. Rosin. Resin hemoperfusion. Letter to the editor.New Engl. J. Med. 285:123 (1971).

    Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  12. E. Iisalo and J. Forsström. Elimination of digoxin during maintenance haemodialysis.Ann. Clin. Res. 6:203–206 (1974).

    CAS  PubMed  Google Scholar 

  13. E. Iisalo. Clinical pharmacokinetics of digoxin.Clin. Pharmacokin. 2:1–16 (1977).

    Article  CAS  Google Scholar 

  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).

    CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  17. U. Klotz. Pathophysiological and disease-induced changes in drug distribution volume: Pharmacokinetic implications.Clin. Pharmacokin. 1:204–218 (1976).

    Article  CAS  Google Scholar 

  18. J. B. Hawkins and P. R. Dorken. Letter to the editor.Lancet 1:839–840 (1969).

    CAS  PubMed  Google Scholar 

  19. J. M. Davis and W. E. Fann. Lithium.Ann. Rev. Pharmacol. 11:285–302 (1971).

    Article  CAS  PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  21. A. Amdisen and H. Skjoldborg. Hemodialysis for lithium poisoning.Lancet 2:213 (1969).

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  23. P. Lous. Plasma levels and urinary excretion of three barbituric acids after oral administration to man.Acta Pharmacol. Toxicol. 10:147–165 (1954).

    Article  CAS  Google Scholar 

  24. P. Lous. Blood serum and cerebrospinal fluid levels and renal clearance of phenemal in treated epileptics.Acta Pharmacol. Toxicol. 10:166–177 (1954).

    Article  CAS  Google Scholar 

  25. O. Svensmark and F. Buchthal. Accumulation of phenobarbital in man.Epilepsia 4:199–206 (1963).

    Article  CAS  PubMed  Google Scholar 

  26. W. J. Waddell and T. C. Butler. The distribution and excretion of phenobarbital.J. Clin. Invest. 36:1217–1226 (1957).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  29. P. F. Gibson and N. Wright. Ethchlorvynol in biological fluids: Specificity of assay methods.J. Pharm. Sci. 61:169–171 (1972).

    Article  CAS  PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  33. E. Martin, T. N. Tozer, L. Sheiner, and S. Riegelman. Clinical pharmacokinetics of phenytoin.J. Pharmacokin. Biopharm. 5:579–596 (1977).

    Article  CAS  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  35. K. Arnold and N. Gerber. The rate of decline of diphenyldantoin in human plasma.Clin. Pharmacol. Ther. 11:121–134 (1970).

    CAS  PubMed  Google Scholar 

  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).

    Article  PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  42. A. K. Done. Salicylate intoxication: Significance of measurement of salicylate in blood in cases of acute ingestion.Pediatrics 26:800–807 (1960).

    CAS  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  45. G. Levy. Pharmacokinetics of salicylate elimination in man.J. Pharm. Sci. 54:959–967 (1965).

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    PubMed  Google Scholar 

  48. N. R. Farid, J. P. Glynn, and D. N. S. Kerr. Hemodialysis in paracetamol poisoning.Lancet 2:396–398 (1972).

    Article  CAS  PubMed  Google Scholar 

  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).

    PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. G. Levy and H. Yamada. Drug biotransformation interactions in man. III. Acetaminophen and salicylamide.J. Pharm. Sci. 60:215–221 (1971).

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  57. D. D. Breimer. Clinical pharmacokinetics of hypnotics.Clin. Pharmacokin. 2:93–109 (1977).

    Article  CAS  Google Scholar 

  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).

    CAS  Google Scholar 

  59. I. A. Cruz, N. C. Cramer, and A. E. Parrish. Hemodialysis in chlordiazepoxide toxicity.J. Am. Med. Assoc. 202:438–440 (1967).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  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).

    PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  65. M. M. Avram and J. T. McGinn. Extracorporeal hemodialysis in phenothiazine overdosage.J. Am. Med. Assoc. 197:142–143 (1966).

    Article  CAS  Google Scholar 

  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).

    Article  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  68. L. Hillestad, T. Hansen, and H. Melson. Diazepam metabolism in normal man.Clin. Pharmacol. Ther. 16:485–489 (1974).

    CAS  PubMed  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  70. J. F. Maher, G. E. Schreiner, and F. B. Westervelt. Acute glutethimide intoxication.Am. J. Med. 33:70–82 (1962).

    Article  CAS  PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  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).

    Article  Google Scholar 

  73. J. Graae and J. Hadefogea. Svaer meprobamat forgitftning behandlet med haemooq peritoneal dialyse.Nordisk Med. 81:601–603 (1969).

    CAS  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  75. L. E. Hollister and G. Levy. Kinetics of meprobamate elimination in humans.Chemotherapia 9:20–24 (1964).

    Article  CAS  Google Scholar 

  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. 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).

    Article  CAS  Google Scholar 

  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).

    Article  Google Scholar 

  79. G. Xanthaky, A. W. Freireich, W. Matusiak, and L. Lukash. Hemodialysis in methyprylon poisoning.J. Am. Med. Assoc. 198:1212–1213 (1966).

    Article  CAS  Google Scholar 

  80. J. M. Mandelbaum and N. M. Simon. Severe methyprylon intoxication treated by hemodialysis.J. Am. Med. Assoc. 216:139–140 (1971).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  82. N. Burnstein and H. K. Stauss. Attempted suicide with methyprylon.J. Am. Med. Assoc. 194:1139–1140 (1965).

    Article  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  CAS  Google Scholar 

  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).

    Article  PubMed  Google Scholar 

  87. J. Rasmussen. Poisoning by amitriptyline, imipramine and nortriptyline.Danish Med. Bull. 13:201–203 (1966).

    CAS  PubMed  Google Scholar 

  88. L. C. Mark. Pharmacokinetics of barbiturates. In H. Matthew (ed.),Acute Barbiturate Poisoning, Excerpta Medica, Amsterdam, 1971, p. 75.

    Google Scholar 

  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).

    CAS  Google Scholar 

  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).

    Article  CAS  PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

  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).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported in part by Grant 16496 from the National Intitutes of Health.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Takki, S., Gambertoglio, J.G., Honda, D.H. et al. Pharmacokinetic evaluation of hemodialysis in acute drug overdose. Journal of Pharmacokinetics and Biopharmaceutics 6, 427–442 (1978). https://doi.org/10.1007/BF01062724

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01062724

Key words

Navigation