Cocktail法研究脉络宁注射液对大鼠CYP1A2、CYP2E1和CYP3A4活性的影响

目的：研究脉络宁注射液对大鼠CYP1A2、CYP2E1和CYP3A4活性的影响。方法：14只大鼠随机均分成临床等效剂量组和高剂量组，连续2周静脉给予脉络宁注射液（临床等效剂量纽，2mL／kg；高剂量组，4mL／kg）前后，均同时灌胃给予3个探针底物（茶碱，30mg／kg；氯唑沙宗，50rag／kg；氨苯砜，20mg/kg），进行采血试验。用HPLC法同时测定大鼠体内各探针的血药浓度，DAS1．0软件计算药动学参数，并以配对t检验对各组大鼠前后两轮主要药动学参数进行差异性比较。结果：在1个给药疗程（14d）内，临床等效剂量组大鼠用药前后，3个探针的药动学参数均无显著性变化（P〉0．05）；高剂量组大鼠用药后，与用药前相比，茶碱的药动学参数没有显著变化（P〉0．05）；氨苯砜和氯唑沙宗的AUC0-24h均有升高趋势（P〈0．05），给药后分别是给药前的1．44倍和1．28倍，同时氯唑沙宗的CL显著降低（P〈0．05）。结论：临床等效剂量脉络宁对大鼠CYP1A2、CYP2E1和CYP3A4活性均无显著影响，而高剂量脉络宁对大鼠CYP2E1和CYP3A4均有弱抑制作用。

Effects of Mailuoning injection on rat activities of CYP1A2,CYP2E1 and CYP3A4 using a three-drug Cocktail approach

AIM: To investigate the effects of Mai-luoning injection on rat activities of CYP1A2, CYP2E1 and CYP3A4. METHODS: 14 rats were randomly and equally divided into two groups, I.e. Clinically-equivalent-dose group and higher-dose group. Two group rats underwent 2-cycle pharmacokinetie experiments before and after being treated with two doses of Mailuoning injection for 14 days, in which the rats were concomitantly administered Theophylline (30 mg/kg), Chlorzoxazone (50 mg/kg) and Dapsone (20 mg/kg) by gastrogavage, followed by blood-withdrawing from orbital bleeding at different intervals within 24 hours. High-performance liquid chromatography (HPLC) was utilized to simultaneously quantitate 3 probe compounds in rat plasma, and DAS 2.0 Software was used to fit plasma concentration-time curve and calculate their corresponding principal pharmacokinetie parameters, among which the statistical differences were evaluated by Paried t-test. RESULTS: In the 14-day administration period, the 2-cycle pharmacokinetie parameters of 3 probes for the clinically-equivalent-dose group rats exhibited insignificant differences (P > 0.05), meanwhile, after being treated with higher-dose Mailuoning injection, there were no significant differences for theophylline pharmacokinetics in rats, but AUC_(0-24 h), of dapsone and chlorzoxazone after treatment were 1.27 and 1.44 times larger than those before treatment, respectively and chlorzoxazone CL/F became smaller. CONCLUSION: Clinically-equivalent-dose Mailuoning injection did not affect the activities of rat CYP1A2, CYP2E1 and CYP3A4; higher-dose Mailuoning injection could not insignificantly change CYP1A2 activity, but could weakly inhibit activities of CYP2E1 and-CYP3A4.