Advertisement

Pharmaceutisch Weekblad

, Volume 9, Issue 2, pp 79–84 | Cite as

Pharmacokinetics in liver disease

  • D. D. Breimer
Pharmacokinetics and Organ Dysfunction

Abstract

Some general pharmacokinetic principles, relevant to understand and predict altered disposition of drugs in liver disease, are reviewed. It is appropriate to differentiate between high- and low-clearance drugs as to the influence of hepatic dysfunction. On intravenous administration highclearance drugs generally show reduced systemic clearance predominantly caused by decreased liver blood flow, whereas on oral administration a considerable increase in systemic availability may occur caused by reduced enzyme activity and (in cirrhosis) bij portacaval shunting. Low-clearance drugs are sensitive to reduced enzyme activity and reduced protein binding. It seems that oxidative reactions are far more affected than conjugation reactions in liver disease. Large inter-patient variability exists in the kinetics of a drug in any type of hepatic disease. The conventional liver-function tests are of no value in predicting altered drug disposition.

Key words

Clearance, hepatic Liver diseases Pharmacokinetics Protein binding 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bond WS. Clinical relevance of the effect of hepatic disease on drug disposition. Am J Hosp Pharm 1978;35:406–14.Google Scholar
  2. 2.
    Williams RL, Mamelok RD. Hepatic disease and drug pharmacokinetics. Clin Pharmacokinet 1980;5:528–47.Google Scholar
  3. 3.
    Williams RL. Drug administration in hepatic disease. N Engl J Med 1983;309:1616–22.Google Scholar
  4. 4.
    Rowland M, Benet LZ, Graham GG. Clearance concepts in pharmacokinetics. J Pharmacokinet Biopharm 1973;1:123–36.Google Scholar
  5. 5.
    Wilkinson GR, Shand DG. A physiological approach to hepatic drug clearance. Clin Pharmacol Ther 1975;18:377–90.Google Scholar
  6. 6.
    Thomson PD, Rowland M, Melmon KL. The influence of heart failure, liver disease and renal failure on the disposition of lidocaine in man. Am Heart J 1971;82:417–21.Google Scholar
  7. 7.
    Williams RL, Blaschke TF, Meffin PJ, Melmon KL, Rowland M. Influence of viral hepatitis on the disposition of two compounds with high hepatic clearance: lidocaine and indocyanine green. Clin Pharmacol Ther 1976;200:290–9.Google Scholar
  8. 8.
    Neal EA, Meffin PJ, Gregory PB, Blaschke TF. Enhanced bioavailability and decreased clearance of analgesics in patients with cirrhosis. Gastroenterology 1979;77:96–102.Google Scholar
  9. 9.
    McHorse TS, Wilkinson GR, Johnson RF, Shenker S. Effect of acute viral hepatitis in man on the disposition and elimination of meperidine. Gastroenterology 1975;68:775–80.Google Scholar
  10. 10.
    Kleinbloesem CH, Van Harten J, Wilson JPH, Van Brummelen P, Danhof M, Breimer DD. Kinetics and haemodynamic effects of nifedipine in patients with liver cirrhosis after i.v. and oral administration. Clin Pharmacol Ther 1986;21:21–8.Google Scholar
  11. 11.
    Bircher J. Hepatic drug disposition in liver disease: consequences for dosage adjustmens. In: Csomós G, Thaler H, eds. Clinical Hepatology. Berlin: Springer-Verlag, 1983:45–51.Google Scholar
  12. 12.
    Klotz U, Avant GR, Hoyumpa A, Shenker S, Wilkinson GR. The effects of age and liver disease in the disposition and elimination of diazepam in adult man. Clin Invest Med 1975;55:347–59.Google Scholar
  13. 13.
    Jochemsen R, Van Beuzekom BR, Spoelstra P, Janssens AR, Breimer DD. Effect of age and liver cirrhosis on the pharmacokinetics of nitrazepam. Br J Clin Pharmacol 1983;15:295–302.Google Scholar
  14. 14.
    Shull HJ, Wilkinson GR, Johnson R, Shenker S. Normal disposition of oxazepam in acute viral hepatitis and cirrhosis. Ann Intern Med 1976;84:420–5.Google Scholar
  15. 15.
    Kraus JW, Desmond PV, Marshall JP, Johnson RF, Shenker S, Wilkinson GR. Effects of aging and liver disease on disposition of lorazepam. Clin Pharmacol Ther 1978;24:411–9.Google Scholar
  16. 16.
    Mangione A, Imhoff TE, Lee RV, Shum LY, Jusko WJ. Pharmacokinetics of theophylline in hepatic disease. Chest 1978;73:616–22.Google Scholar
  17. 17.
    Williams RL, Blaschke TF, Meffin PJ, Melmon KL, Rowland M. Influence of acute viral hepatitis on disposition and plasma binding of tolbutamide. Clin Pharmacol Ther 1977;21:301–9.Google Scholar
  18. 18.
    Spoelstra P. Antipyrine metabolism in liver disease. Leiden: State University of Leiden, 1986. Dissertation.Google Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1987

Authors and Affiliations

  • D. D. Breimer
    • 1
  1. 1.Center for Bio-Pharmaceutical Sciences, Division of PharmacologyState University of LeidenRA LeidenThe Netherlands

Personalised recommendations