盐酸米那普仑在中国健康人体中的群体药代动力学研究  

Population pharmacokinetics of milnacipran in Chinese healthy volunteers

作　　者：阮灿军[1] 赵立波[3] 果伟[1] 李文标[1] 董芳[1] 翟屹民[1] 王传跃[2] 

机构地区：[1]首都医科大学附属北京安定医院临床精神药理实验室及北京市精神疾病诊断与治疗重点实验室 [2]首都医科大学附属北京安定医院精神病学系,精神疾病诊断与治疗北京市重点实验室,北京脑重大疾病研究精神分裂症研究所,北京100088 [3]首都医科大学附属北京儿童医院药学部,北京100045

出　　处：《中国临床药理学杂志》2017年第4期323-326,共4页The Chinese Journal of Clinical Pharmacology

基　　金：首都卫生发展专项基金资助项目(2014-2-2122);首都临床特色应用研究与成果推广项基金资助项目(z15110000401580);北京市医院管理局临床医学发展专项基金资助项目(ZYLX201403)

摘　　要：目的评价盐酸米那普仑在中国健康人群的群体药代动力学特征及可能的影响因素。方法单次给药共有12例受试者(男女各半),进行3个剂量组(25,50,100 mg)的拉丁方三交叉自身对照设计,每个服药周期洗脱期为7 d;多次给药组12例受试者(男女各半),连续8 d给药(给药剂量滴定至每天100 mg,每次50 mg)。液质联用法(HPLC-MS/MS)测定盐酸米那普仑的血浆浓度,以非线性混合效应模型(NONMEN)进行分析,获得群体药代动力学参数。结果最终模型为Ⅰ室模型,模型的药代动力学参数估计值(95%置信区间)分别为:清除率(CL)为37.53~44.16(40.84±1.69)L·h^(-1),表观分布容积(V)为382.89~433.37(408.13±12.86)L,吸收常数(Ka)为0.81~1.31(1.06±0.13)/h,性别和体重对盐酸米那普仑的清除无影响。结论本模型稳定,能较好的拟合盐酸米那普仑的群体药代动力学特征。Objective To investigate the population pharmacokinetic characteristics of milnacipran in Chinese healthy volunteers and factors co- variables that might impact its clearance. Methods The clinical data and blood samples were collected from a pharmacokinetics（ PK）study（ n = 24） which was designed as a randomized,three- way crossover,single dose（ 25,50 or 100 mg） and in multiple doses for 8 d（ up to 100 mg·d^-1 administered as 50 mg twice daily） in Chinese healthy volunteers. Both the single and multiple- dose studies included 12volunteers（ six males and six females）. The concentration of milnacipran in plasma was analyzed by HPLC- MS / MS. Non- linear mixed- effects model（ NONMEM） was used to assess the influence of demographic characte-ristics on PK characters of milnacipran. The final model was diagnosed by goodness- of- fit plots and evaluated by bootstrap methods. Results A one- compartment model was developed to capture the milnacipran pharmacokinetics. Typical value of clearance（ CL）,the volume of distribution（ V）,and maximum absorption rate（ Ka） were37. 53- 44. 16（ 40. 84 ± 1. 69） L·h^-1, 382. 89- 433. 37（ 408. 13 ± 12. 86） L and 0. 81- 1. 31（ 1. 06 ± 0. 13） /h,respectively,and age or sex had no influence on CL of milnacipran. No obvious bias was found by bootstrap method. Conclusions The developed model can capture milnacipran pharmacokinetics well in healthy volunteers. Ageand genderhad no influenceon minacipran PK profiles in healthy subjects.

关 键 词：盐酸米那普仑 群体药代动力学模型 液质联用法 

分 类 号：R969.1[医药卫生—药理学]