与复方新诺明合用对罗格列酮代谢的影响

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (5): 531-535.

与复方新诺明合用对罗格列酮代谢的影响

何君^1,2, 段丽芳^1,3, 张伟¹, 李智¹, 范岚¹, 沈杰¹, 周宏灏¹

¹中南大学临床药理研究所, 长沙410078, 湖南;
²中国医学科学院实验动物研究所新药安全评价研究中心, 北京100020;
³北京大学深圳医院药剂科, 深圳518026, 广东

收稿日期:2009-03-25 修回日期:2009-06-11 发布日期:2020-11-09
通讯作者: 周宏灏, 男, 博士生导师, 中国工程院院士, 研究方向:药理学。Tel:0731-4805379 E-mail:hhzhou2003 @163. com
作者简介:何君, 女, 博士, 助理研究员, 研究方向:药理学。Tel:010-63031045, 13717830490 E-mail:jun he92 @163. com
基金资助:
国家自然科学基金资助项目(30801421);教育部青年教师基金资助项目(20070533002)

Effects of rosiglitazone coadministration with compound sulfamethoxazole on the pharmacokinetics

HE Jun ^1,2, DUAN Li-fang ¹, ZHANG Wei ¹, LI Zhi ¹, FAN Lan ¹, SHEN Jie ¹, ZHOU Hong-hao¹

¹Institute of Clinical Pharmacology, Central SouthUniversity, Changsha 410078, Hunan, China;
²Centre for Safety Evaluation and Research of Drugs, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing 100020, China;
³Pharmacy Department of Shenzhen Hospital of Peking University, Shenzhen 518026, Guangdong, China

Received:2009-03-25 Revised:2009-06-11 Published:2020-11-09

摘要/Abstract

摘要： 目的:研究与复方新诺明合用对罗格列酮在体内的代谢动力学参数的影响, 对二者在临床合用的安全性进行探讨。方法:采用随机、双盲、双周期交叉方法, 测定10 名中国男性健康志愿者在连续口服复方新诺明4. 5 d(每天2 次, 每次1 g)后, 单次口服4 mg 罗格列酮后各时间点时的血浆药物浓度, 计算出罗格列酮在体内相关药代动力学参数。采用HPLC-MS/MS 法测定血浆中罗格列酮及其主要代谢产物N-去甲基罗格列酮的浓度。结果:复方新诺明与罗格列酮合用时, 对罗格列酮及其主要代谢产物N-去甲基罗格列酮的血药峰浓度(C_max)和达峰时间(t_max)没有影响(P>0. 05), 但罗格列酮的AUC_0-48增加了40% (P =0. 000)[从(6768 ±900)ng·mL^-1·h 改变为(9485±1638)ng·mL^-1 ·h)], 半衰期t_1/2延长了44% (P=0. 007)[由(4. 4 ±0. 8)h 延长到(6. 1 ±1. 2)h], N-去甲基罗格列酮转化率的AUC_0-48 降低为59. 8% (P =0. 001)。结论:复方新诺明降低罗格列酮转化率, 增加血浆罗格列酮浓度。

关键词: 复方新诺明, 罗格列酮, 代谢动力学参数, HPLC-MS/MS

Abstract: AIM:To investigate the effect of compound sulfamethoxazole on the rosiglitazone pharmacokinetics in normal Chinese subjects and assess the safety when they are coadministrated in clinic. METHODS: Ten male healthy volunteers completed a randomized, two-period, double-blind crossover study. Volunteers received single dose rosiglitazone (4 mg)in the presence and absence of compound sulfamethoxazole 1g given twice daily for 4. 5 days. The plasma drug concentrations were determined at each time point after oral rosiglitazone. The related pharmacokinetical parameters in vivo were computed. The concentrations of rosiglitazone and N-demethylrosiglitazone were assessed by HPLC-MS/MS. RESULTS:The C_max and t_maxof rosiglitazone and N-demethylrosiglitazone were not changed by compound sulfamethoxazole treatment, respectively(P >0. 05).But the AUC_0-48 of rosiglitazone was increased by 40% (P =0. 000)from (6768 ±900)ng·mL^-1·h to (9485 ±1638)ng·mL^-1·h, and the t_maxwas increased by 44% (P =0. 007)from (4. 4 ±0. 8)to (6. 1 ±1. 2)h. The AUC_0-48 of biotransformation rate of N-demethylrosiglitazone/rosiglitazone was decreased to 59. 8% (P =0. 001).CONCLUSION: Compound sulfamethoxazole decreases the rosiglitazone biotransformation rate and increases the plasma rosiglitazone concentrations in healthy volunteers when they are co-administrated.

Key words: compound sulfamethoxazole, rosiglitazone, pharmacokinetical parameters, HPLC-MS/MS

中图分类号:

R969. 1

何君, 段丽芳, 张伟, 李智, 范岚, 沈杰, 周宏灏. 与复方新诺明合用对罗格列酮代谢的影响[J]. 中国临床药理学与治疗学, 2009, 14(5): 531-535.

HE Jun , DUAN Li-fang , ZHANG Wei , LI Zhi , FAN Lan , SHEN Jie , ZHOU Hong-hao. Effects of rosiglitazone coadministration with compound sulfamethoxazole on the pharmacokinetics[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(5): 531-535.

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