Ohmori S, Horie T, Hayashi S, Kitada M
Division of Pharmacy, Chiba University Hospital, Faculty of Medicine, Japan.
Pharmacology. 1994 Mar;48(3):137-42. doi: 10.1159/000139172.
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.
我们研究了临床上用作抗生素的氨曲南连续给药对非人灵长类动物混合功能氧化酶系统的影响。用40至300mg/kg剂量的氨曲南治疗食蟹猴4周，导致肝微粒体P450含量显著降低。另一方面，用氨曲南治疗后，肝中细胞色素b5含量和NADPH - 细胞色素c（P450）还原酶活性未观察到显著变化。用氨曲南治疗食蟹猴后，肝微粒体中睾酮6β - 羟化酶的活性降低，但2β - 和16α - 羟化酶的活性未降低。尽管食蟹猴中作为2A酶的P450 CMLb含量未变，但氨曲南治疗也降低了归类于3A亚家族的P450 CMLc的含量。从这些结果中，我们得出结论，氨曲南降低了食蟹猴肝微粒体中的P450 CMLc。
