Enhancement of hepatic drug metabolism by glutethimide in patients with liver disease

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Abstract
A controlled study of the effects of glutethimide on antipyrine metabolism was performed to ascertain how patients with varying degrees of liver damage responded to microsomal enzyme inducing agents. The administration of 250 mg glutethimide daily for one week resulted in significant enhancement of antipyrine metabolism in 4 patients with compensated cirrhosis and 5 patients with features of hepatic failure as well as 7 control subjects without liver disease. Even patients with very severe liver disease did undergo microsomal enzyme induction. Changes in antipyrine half-life after glutethimide were directly proportional to the original antipyrine half-life so that the greatest absolute alterations due to enzyme induction occurred in patients with the most severely impaired hepatic function. These results indicate that not only is antipyrine metabolism severely impaired in patients with liver failure, but elimination rates are markedly altered by enzyme inducing agents. Thus, although these results cannot be extrapolated to all inducers of hepatic microsomal enzymes nor to all drugs metabolized by microsomal oxidases, it is suggested that safe and effective management of drug therapy in these patients requires measurement of plasma levels.