Effects of platinum and palladium salts on parameters of drug metabolism in rat liver

Abstract

The effects of various salts of platinum of palladium were determined on the parameters of the microsomal mixed-function oxidase system from rat liver. The intraperitoneal injection of PtCl4 or Pd(NO3)2 increased the hexobarbital-induced sleeping time in vivo and generally decreased the aminopyrine demethylase and the content of cytochrome P-450 in isolated hepatic microsomes. The dietary administration of various salts of platinum or palladium for 1 wk generally decreased or had no effect on the parameters of drug metabolism by isolated microsomes and after 4 or more wk generally had no effect on, or increased, the parameters. The addition of 0.15-0.2 mM PtCl4 or 0.2-0.3 mM Pd(NO3)2 to the incubation medium (containing 5 mM MgCl2) inhibited the aminopyrine demethylase of isolated hepatic microsomes by 50%.