右旋佐匹克隆在中国健康受试者中的药代动力学研究  

Pharmacokinetic study of eszopiclone in healthy Chinese volunteers

作　　者：武峰[1] 赵秀丽[1] 魏敏吉[2] 王淑民[1] 周辉[1] 郭韶洁[1] 张朴[2] 

机构地区：[1]首都医科大学附属北京同仁医院国家药物临床试验机构,北京100730 [2]北京大学第一医院临床药理研究所,北京100191

出　　处：《中国临床药理学杂志》2015年第24期2423-2426,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价中国健康受试者单次服用不同剂量以及连续多次服用右旋佐匹克隆的药代动力学特征。方法单次给药组12名受试者随机、交叉、空腹口服右旋佐匹克隆1.5,3.0,6.0 mg;多次给药组8名受试者每天空腹口服右旋佐匹克隆3.0 mg,连续7 d。用HPLC-MS/MS法测定不同时间点血浆右旋佐匹克隆的浓度,用3P97程序计算药代动力学参数并对给药剂量与C_(max)和AUC进行线性相关性分析。结果单次口服右旋佐匹克隆1.5,3.0,6.0 mg的药代动力学参数如下:C_(max)分别为(18.08±4.65),(38.29±15.41),(76.38±23.34)ng·mL^(-1);t_(max)分别为(0.94±0.39),(1.04±0.63),(1.08±0.51)h;AUC_(0-t)分别为(110.90±23.06),(227.36±62.41),(504.10±140.13)ng·mL^(-1)·h;t_(1/2)分别为(5.84±1.03),(5.53±1.91),(6.17±1.23)h。多次给药的药代动力学参数如下:C_(max)为(33.43±5.63)ng·mL^(-1),t_(max)为(1.38±0.50)h,AUC_(ss)为(263.30±51.21)ng·mL^(-1)·h,t_(1/2)为(6.74±1.49)h。主要不良事件包括口苦或味觉异常等,停药后均自行缓解或消失。结论右旋佐匹克隆在1.5~6.0 mg内呈剂量比例关系的线性药代动力学特征,该药用于人体的安全性及耐受性良好。Objective To investigate the pharmacokinetic characters of eszopiclone after single and multiple- dose oral administration in healthy adult Chinese volunteers.Methods In single- dose study,12 subjects were given oral administrations of 1.5,3.0 and 6.0 mg eszopiclone in an open- label,randomized,crossover fashion.In multiple- dose study,8subjects were given 3.0 mg eszopiclone once daily consecutively for 7days.Blood samples were collected in different time and plasma eszopiclone were determined using a validated liquid chromatography/mass spectrometry（LC/MS/MS） assay.The pharmacokinetic characters were calculated and linearity between C_（max）,AUC and the administered dose was analyzed.Results The main pharmacokinetic parameters of eszopiclone after single- dose administration were as follows：doses of 1.5,3.0 and 6.0 mg,C_（max） of（18.08±4.65）,（38.29±15.41） and（76.38±23.34）ng·mL^-1;t_（max） of（0.94±0.39）,（1.04±0.63） and（1.08±0.51） h;AUC_（0-t） of（110.90±23.06）,（227.36±62.41） and（504.10±140.13） ng·mL^-1 · h,t_（1/2） of（5.84 ±1.03）,（5.53±1.91）and（6.17±1.23） h.After multiple- dose administration,the main pharmacokinetic parameters were C_（max） at（33.43±5.63） ng·mL^-1,t_（max） at（1.38±0.50） h,AUC_（ss） at（263.30±51.21） ng · mL^-1 · h and t_（1/2） at（6.74±1.49） h.The common adverse events included bitter or abnormal taste and et al.All the adverse events resolved without any medication.Conclusion The pharmacokinetic character of eszopiclone is linear and dose-proportional over the range of 1.5-6.0 mg.Eszopiclone appears to have good safety and is well tolerated.

关 键 词：右旋佐匹克隆 药代动力学 液质联用法 安全性 

分 类 号：R971.3[医药卫生—药品] R969.1[医药卫生—药学]