Aztreonam decreases hepatic microsomal cytochrome P450 in cynomolgus monkeys.

Abstract

We examined the effect of successive administrations of aztreonam, which is used clinically as an antibiotic, on the mixed function oxidase system in non-human primates. Treatment of cynomolgus monkeys with aztreonam at doses of between 40 and 300 mg/kg for 4 weeks resulted in a significant decrease in the content of hepatic microsomal P450. On the other hand, no significant change was observed in hepatic cytochrome b5 content and NADPH-cytochrome c (P450) reductase activity following treatment with aztreonam. The activity of testosterone 6 beta-hydroxylase, but not 2 beta- and 16 alpha-hydroxylases in hepatic microsomes, was decreased following the treatment of cynomolgus monkeys with aztreonam. The content of P450 CMLc, which is classified into the 3A subfamily, was also decreased by aztreonam treatment although the content of P450 CMLb, which is a 2A enzyme in cynomolgus monkeys, was unchanged. From these results, we concluded that aztreonam decreased P450 CMLc in hepatic microsomes of cynomolgus monkeys.