Inhibition of hepatic microsomal drug metabolism by the hydrazines Ro 4-4602, MK 486, and procarbazine hydrochloride.

Abstract

Preliminary experiments were undertaken to examine the effect of three hydrazine derivatives, viz. Ro 4-4602, MK 486, and procarbazine hydrochloride, on hepatic microsomal drug metabolism in rats. All three compounds when given as pretreatment significantly prolonged pentobarbital sleeping time. In vitro, the hepatic microsomal N-demethylation of aminopyrine was inhibited. It is concluded that all three drugs are possible sources of clinically significant drug interaction when administered in combination with other agents which undergo hepatic biotransformation.