美托洛尔在经左氧氟沙星诱导的大鼠肝微粒体P450系统中的代谢特征

Metabolic characteristics of metoprolol in the cytochrome P450 of rat liver microsomes induced by levofloxcain

采用正常及经不同剂量 ( 80、160、2 40mg/kg ,ip ,7d)左氧氟沙星诱导的大鼠肝微粒体 ,研究美托洛尔代谢特征及酶动力学参数。HPLC法用于美托洛尔浓度的测定。研究结果显示 ,经不同剂量的左氧氟沙星诱导后 ,大鼠的肝重及P45 0含量均明显降低 ,中剂量组及高剂量组分别与对照组及低剂量组比较有极显著性差异 (P <0 0 1)。对美托洛尔的代谢率随诱导剂剂量的增加而降低 ,低剂量组与对照组比较无差异 ,中剂量组及高剂量组分别与对照组及低剂量组比较有统计学意义。酶动力学参数测定结果显示 ,经左氧氟沙星诱导的细胞色素P45 0酶系统对美托洛尔代谢的Km 和Vmax值均增加 ,与对照组比较有极显著性差异 (P <0 0 1)。结论 :左氧氟沙星可抑制大鼠肝微粒体细胞色素P45 0系统对美托洛尔的代谢。

Metoprolol were metabolized in vitro by cytochrome P450 with different dosage of levoflo xacin in normal and induced rats. An HPLC method was used to determine the metoprolol concentration. The substate concentration time curve and enzyme parameters ( K m, V max and Cl int ) of each liver microsome of metoprolol were obtained. Results showed that liver weight, quantity of cytochrome P450 and metabolized ratio of metoprolol were significantly decreased, and enzyme parameters ( K m and V max ) were significantly increased after rat liver microsomes were induced by levofloxacin at different dosage. The differences of these changes were statistic significance between middle dosage induced group, high dosage induced group and control group. In conclusion, levofloxacin significantly inhibited metabolism of metoprolol in the cytochrome P450 of rat hepatic microsomes.