中国男性健康志愿者口服去甲文拉法辛缓释片对映体选择性药动学研究  

The enantioselective pharmacokinetic study of desvenlafaxine sustained release tablet in Chinese healthy male volunteers after oral administration

作　　者：陈银霞[1,2] 杜江波[2] 张逸凡[2] 陈笑艳[2] 钟大放[1,2] 

机构地区：[1]浙江工业大学药学院,浙江杭州310014 [2]中国科学院上海药物研究所,上海201203

出　　处：《药学学报》2015年第4期486-491,共6页Acta Pharmaceutica Sinica

基　　金：江苏豪森药业股份有限公司对该研究给予全力支持和帮助

摘　　要：建立手性LC-MS/MS法同时测定人血浆中去甲文拉法辛（desvenlafaxine,DVS）对映异构体,并应用于其在中国人体内的立体选择性药动学研究。本法采用d6-去甲文拉法辛作内标,分析柱为Astec ChirobioticTM V手性色谱柱（150 mm×4.6 mm,5μm）。R-去甲文拉法辛、S-去甲文拉法辛在0.500~150 ng·m L-1内线性均良好（r2〉0.99）。本方法成功应用于12名健康受试者空腹口服琥珀酸去甲文拉法辛缓释片100 mg后人体立体选择性药动学研究。结果表明在中国健康人体内去甲文拉法辛两对映异构体药动学参数基本相似,而各个对映体的Cmax和AUC参数均是文献报道黑人和白人受试者相应参数的1.5倍左右。A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine（DVS） enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard（IS）. Chromatographic separation was performed on the Astec ChirobioticTM V chiral column（150 mm × 4.6 mm, 5 μm）. The assay was linear over the concentration range of 0.500-150 ng·m L-1 for both enantiomers（r2〉 0.99）. The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC0-t and Cmax of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.

关 键 词：LC-MS/MS 去甲文拉法辛 对映异构体 人体药动学 

分 类 号：R917[医药卫生—药物分析学]