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

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (4): 386-390.

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

陈为烤¹, 居文政², 许黎君¹, 刘史佳², 谈恒山³

¹南京中医药大学, 南京210029, 江苏;
²南京中医药大学附属江苏省中医院临床药理科, 南京210029, 江苏;
³南京军区总医院临床药理科, 南京210002, 江苏

收稿日期:2009-03-12 修回日期:2009-04-01 发布日期:2020-10-29
通讯作者: 居文政,男,博士,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:陈为烤,男,硕士在读,研究方向:体内外药物代谢研究。Tel:025-81588201 E-mail:weikao1018@126.com
基金资助:
科技部“十一五”支撑计划课题—药物临床研究关键技术研究与应用(2006BAI14B07)

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

CHEN Wei-kao¹, JU Wen-zheng², XU Li-jun¹, LIU Shi-jia², TAN Heng-shan³

¹School of Pharmaceutical Sciences, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu, China;
²Department of Clinical Pharmacology, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing 210029, Jiangsu, China;
³Department of Clinical Pharmacology, General Hospital of Nanjing Military Base, Nanjing 210002,Jiangsu, China

Received:2009-03-12 Revised:2009-04-01 Published:2020-10-29

摘要/Abstract

摘要： 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(临床等效剂量组,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,50mg/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AUC_0-24h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。

关键词: 脉络宁注射液, 细胞色素P450, 茶碱, 氯唑沙宗, 氨苯砜

Abstract: AIM: To investigate the effects of Mailuoning injection on rat activities of CYP1A2, CYP2E1 and CYP3A4.METHODS: 14 rats were randomly and equally divided into two groups, i.e.clinicallyequivalent-dose group and higher-dose group.Two group rats underwent 2-cycle pharmacokinetic experiments before and after being treated with two doses of Mailuoning injection for 14 days, in which the rats were concomitantly administered Theophylline (30mg/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 pharmacokinetic parameters, among which the statistical differences were evaluated by Pariedt-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 Mailuoning injection, there were no significant differences for theophylline pharmacokinetics in rats, but AUC0-24 h of dapsone and chlorzoxazone after treatment were 1.27 and 1.44 times larger than those before treatment, respectively and chlorzoxazone CLF 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.

Key words: Mailuoning injection, cytochrome P450, Theophylline, Chlorzoxazone, Dapsone

中图分类号:

R969.1

陈为烤, 居文政, 许黎君, 刘史佳, 谈恒山. Cocktail法研究脉络宁注射液对大鼠CYP1A2、CYP2E1和CYP3A4活性的影响[J]. 中国临床药理学与治疗学, 2009, 14(4): 386-390.

CHEN Wei-kao, JU Wen-zheng, XU Li-jun, LIU Shi-jia, TAN Heng-shan. Effects of Mailuoning injection on rat activities of CYP1A2, CYP2E1 and CYP3A4 using a three-drug Cocktail approach[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(4): 386-390.

参考文献

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