Determinants of serum antipyrine half-lives in patients with liver disease

Abstract

Antipyrine has been used as a model drug to investigate the effects of liver disease on drug metabolism in man. A prolongation in antipyrine half-life (T(1/2)) was found in patients with liver disease, patients with chronic liver disease showing a greater increase than those with acute, reversible pathology. The most marked prolongation in T(1/2) was found in association with hypoalbuminaemia and hypoprothrombinaemia, suggesting that the cause for these changes was defective protein synthesis of microsomal enzyme protein. This hypothesis was supported by demonstrating that enzyme-inducing agents, which are known to increase the amount of microsomal enzyme protein, reduced the antipyrine half-life.