黄葵胶囊对大鼠CYP450酶的影响

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (4): 367-371.

黄葵胶囊对大鼠CYP450酶的影响

刘子修¹, 刘史佳², 居文政^1,2, 谈恒山³

¹南京中医药大学药学院,南京 210009,江苏;
²南京中医药大学附属医院临床药理科,南京 210029,江苏;
³南京军区总医院,南京 210002,江苏

收稿日期:2010-03-04 修回日期:2010-03-29 发布日期:2020-09-17
通讯作者: 居文政,男,主任药师,博士生导师,研究方向:中药临床药代动力学。Tel:025-86617141-80518 E-mail:njwz1008@jlonline.com
作者简介:刘子修,男,硕士研究生,研究方向:中药学。E-mail: liuzixiu3221@126.com
基金资助:
中药新药临床评价研究技术平台(南京)建设(2008ZX09312-004);江苏省中医药领军人才项目(2009)

Effects of Huangkui Capsule on the P450 activities in rats

LIU Zi-xiu¹, LIU Shi-jia², JU Wen-zheng^1,2, TAN Heng-shan³

¹Nanjing University of Traditional Chinese Medicine,Nanjing 210029,Jiangsu, China;
²Department of Clinical Pharmacology,Affiliated Hospital of Nanjing University of Traditional Chinese Medicine,Nanjing 210029,Jiangsu,China;
³General Hospital of Armed Forces of Nanjing,Nanjing 210002,Jiangsu, China

Received:2010-03-04 Revised:2010-03-29 Published:2020-09-17

摘要/Abstract

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。

关键词: 黄葵, CYP450, 茶碱, 氨苯砜, 氯唑沙宗

Abstract: 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 AUC_0-24h of chlorzoxazone after treatment was 1.75 times larger than that before treatment(P<0.05), in addition AUC_0-24h 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.

Key words: Abelmoschus moschatus Medicus, CYP450, Theophylline, Dapsone, Chlorzoxazone

中图分类号:

R969

刘子修, 刘史佳, 居文政, 谈恒山. 黄葵胶囊对大鼠CYP450酶的影响[J]. 中国临床药理学与治疗学, 2010, 15(4): 367-371.

LIU Zi-xiu, LIU Shi-jia, JU Wen-zheng, TAN Heng-shan. Effects of Huangkui Capsule on the P450 activities in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(4): 367-371.

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