摘要
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AUC_(0-24h)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AUC_(0-24h)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。
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.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2010年第4期367-372,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
中药新药临床评价研究技术平台(南京)建设(2008ZX09312004)
江苏省中医药领军人才项目(2009)
关键词
黄葵
CYP450
茶碱
氨苯砜
氯唑沙宗
Abelmoschus moschatus Medicus
CYP450
Theophylline
Dapsone
Chlorzoxazone
