Demonstration of H2O2 production in vivo during aminopyrine metabolism and phenobarbital induction.

It has been shown previously that, by using methanol and a catalase inhibitor, 3-amino-1, 2, 4,-triazole, changes in hepatic H2O2 production in vivo can be detected. Using this method in guinea pigs and rats we could demonstrate increased H2O2 production during metabolism in vivo of aminopyrine, especially in phenobarbital-pretreated animals. In contrast, administration of antipyrine does not lead to H2O2 production. In the guinea pigs, phenobarbital induction also stimulates the H2O2 production in vivo without administration of exogenous substrates. The rate and extent of this additional H2O2 production depend on the induction state, drug metabolism and species; the major findings are in agreement with and extend previous research in vitro on microsomes, isolated hepatocytes and perfused liver.