Interaction of pentobarbital, diphenylhydantoin and digitoxin with ethanol in the isolated perfused guinea-pig liver

Abstract

In the isolated guinea-pig liver the interactions of ethanol with the metabolism of three drugs (14C-pentobarbital, 14C-diphenylhydantoin, and 2H-digitoxin) has been investigated. The disappearance of ethanol could be described by zero-order kinetics and was not influenced by the three drugs. In the case of 14C-pentobarbital and 14C-diphenylhydantoin after a short period of distribution disappearance of radioactivity was faster under the influence of ethanol, whereas radioactivity in liver tissue was increased. The radioactivity accumulated in the liver tissue predominantly represented the unchanged drugs suggesting that the inhibition of drug metabolism by ethanol was the cause of the altered distribution. In the case of 3H-digitoxin ethanol did neither significantly influence the distribution of radioactivity nor the pronounced biliary excretion. However there exists some evidence for a minor inhibition of 3H-digitoxin's metabolism by ethanol.