氟喹诺酮类药物对大鼠肝外组织药物代谢酶的影响

目的:探讨氟喹诺酮类药物(FQs)对大鼠肺、脑、肾、小肠中细胞色素P450(CYP)含量、氨基比林N- 脱甲基酶(AMND)、红霉素N-脱甲基酶(ERND)活性的影响。方法:体外实验中环丙沙星、妥苏沙星和司帕沙星的药物终浓度均为1 mmol·L-1;体内实验按1 mmol·kg-1剂量灌胃,qd×7。制备大鼠肺、脑、肾、小肠S9,分光光度法测定CYP含量、AMND及ERND活性变化。结果:大鼠肺、肾组织CYP含量低;3种药物可不同程度地抑制各组织AMND活性(P<0．05)。肾和小肠中可测到ERND活性,而肺、脑中未测到;给药后肾、小肠 ERND活性有降低趋势,但大多无显著差异。结论:FQs对肝外组织CYP含量无显著影响,对AMND活性有抑制作用,对ERND有抑制趋势。

Effects of fluoroquinolones on drug-metabolizing enzymes of extra-hepatic tissue in rats

AIM: Fluoroquinolones have gained widespread use in the treatment of a broad range of bacterial infections and can decrease P450 of human and rat.But there are few published reports of the effects of fluo- roquinolones on drug-metabolizing enzymes of extra-hepatic tissue.This paper explores the effects of fluroquinolones (FQs) on the content of cytochrome P450 and the activities of AMND and ERND in the lung,brain,kidney,and small intestine of rats. METHODS: The terminal concentration of ciprofloxacin, tosufloxacin and sparfloxacin was 1 mmol·L-1 in vitro. In vivo the rats were fed with drugs (1 mmol·kg-1 weight) respectively for 7 d,once per day. The lung, brain, kidney and small intestine of the rats were removed and centrifuged to obtain the S9 mix.The content of P450 and the activities of AMND and ERND in the S9 mix were tested with a spectrophotometer. RESULTS: Low-level concentration of cytochrome P450 was detected in the lung and kidney tissues. The AMND activities of the tissues were inhibited by the three kinds of FQs used (P < 0.05). Low level of ERND activity in the kidney and small intestine were detected, but was not detected in the lung and brain. Although the ERND activity decreased after FQs were added to the kidney and small intestine, there was no significant difference. CONCLUSION: FQS have no significant effect on cytochrome P450 in extra-hepatic tissue,but can inhibit the activities of AMND in some extra-hepatic tissues and have the trend to inhibit the activities of ERND.