黄葵胶囊对大鼠CYP450酶的影响

目的：研究黄葵胶囊对大鼠CYP1A2、CYP2E1、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周灌胃给予黄葵胶囊（临床等效剂量组,0.75 g/kg;高剂量组,2 g/kg）前后,均同时灌胃给予3个探针底物（茶碱,30 mg/kg;氨苯砜,20 mg/kg;氯唑沙宗,50 mg/kg）,采血测定。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检验对两组大鼠前后两轮主要药动学参数进行差异性比较。结果：临床等效剂量组大鼠给药后,与给药前相比,茶碱、氨苯砜和氯唑沙宗的药动学参数无统计学变化（P〉0.05）;高剂量组大鼠给药后,氨苯砜的AUC0-24h与给药前相比,有降低趋势（P〈0.05）,是给药前的0.63倍;氯唑沙宗的AUC0-24h与给药前相比,有升高趋势（P〈0.05）,是给药前的1.75倍。结论：临床等效剂量黄葵胶囊对大鼠CYP1A2、CYP3A4、CYP2E1活性均无显著影响;而高剂量黄葵胶囊对大鼠CYP3A4有弱诱导作用,对CYP2E1有弱抑制作用。

Effects of Huangkui Capsule on the P450 activities in rats

AIM：To investigate the effects of Huangkui Capsule on rat activities of CYP1A2, CYP3A4 and CYP2E1.METHODS：14 rats were randomly and equally divided into two groups：clinically-equivalent-dose group and higher-dose group.Two group rats underwent 2-cycle pharmacokinetic experiments before and after being treated with two doses of Huangkui Capsule 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 DAS1.0 Software was used to fit plasma concentration-time curve and calculate their corresponding principal pharmacokinetic parameters,among which the statistical differences were evaluated by Paried t-test.RESULTS： In the 14-day administration period,the 2-cycle pharmacokinetic parameters of 3 probes for the clinically-equivalent-dose group rats exhibited insignificant differences（P〈0.05）, meanwhile,after being treated with higher-dose Huangkui Capsule,there were no significant differences for theophylline pharmacokinetics in rats,but AUC0-24 h of chlorzoxazone after treatment was 1.75 times larger than that before treatment（P〈0.05）,in addition AUC0-24 h of dapsone after treatment were 0.63 times of it before treatment（P〈0.05）.CONCLUSION：Clinically -equivalent-dose Huangkui Capsule did not affect the activities of rat CYP1A2,CYP3A4 and CYP2E1;higher-dose Huangkui could not insignificantly change CYP1A2 activity,but could weakly inhibit activities of CYP2E1 and induce CYP3A4.