Clinical Relevance of the Effect of Hepatic Disease on Drug Disposition

Abstract

The effect of hepatic disease on the metabolism of drugs is reviewed. Drugs discussed include those acting on the central nervous system (phenobarbital, pentobarbital, amobarbital, diazepam, chlordiazepoxide, oxazepam, clorazepate, chlorpromazine, morphine, meperidine, phenytoin); those acting on the cardiopulmonary system (digoxin, digitoxin, lidocaine, theophylline); antineoplastic agents (azathioprine, 6-mercaptopurine, doxorubicin), antimicrobials (carbenicillin, ampicillin, nafcillin, chloramphenicol, clindamycin, lincomycin, rifampin, isoniazid, aminosalicylic acid) and antiinflammatory agents (phenylbutazone, prednisone). The effect of hepatic dysfunction on drug disposition is not consistent or predictable. The efficiency with which drugs are metabolized by the liver, the extent of drug plasma binding, and the etiology and stage of the hepatic disorder are each important in determining whether drug disposition will be altered.