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Clinical Pharmacokinetics

, Volume 2, Issue 1, pp 32–44 | Cite as

Protein Binding and Kinetics of Drugs in Liver Diseases

  • Terrence F. Blaschke
Article

Summary

Although the liver is the major site for drug biotransformation, the effect of hepatic dysfunction on drug disposition has not been consistent or predictable. Most early studies of drug kinetics in liver disease measured only half-life. Only in the past few years has it been realised that liver diseases can affect drug absorption, hepatic metabolism, tissue distribution, and protein binding, which complicate interpretation of any change, or lack of change in drug half-life. Furthermore, it is now apparent that the efficiency with which a drug is metabolised by the liver, the extent of binding to blood constituents, and the aetiology and stage of the hepatic disorder are each important in determining whether significant alterations in drug disposition will occur.

A pharmacokinetic perfusion model which takes into account many of the above factors has been proposed, and appears to be useful for predicting changes in the disposition of rapidly metabolised compounds. Nevertheless, the state of knowledge about those factors which limit the rate of metabolism of individual drugs or classes of drugs is inadequate, and no general model or guidelines which are useful clinically have been developed.

Patients with hepatic disorders may show increases or decreases in sensitivity independent of alterations in drug disposition. The clinician caring for such patients must be cautious about the use of any drugs, and rely heavily on careful patient observation to determine efficacy or toxicity.

Keywords

Liver Disease Clinical Pharmacology Plasma Protein Binding Tolbutamide Antipyrine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© ADIS Press 1977

Authors and Affiliations

  • Terrence F. Blaschke
    • 1
  1. 1.Department of MedicineStanford University School of MedicineStanfordUSA

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