中国临床药理学杂志2017，Vol.33Issue(4)：323-326,4.DOI:10.13699/j.cnki.1001-6821.2017.04.010
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
摘要
Abstract
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 cross-over,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 12 volunteers (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) were 37.53-44.16 (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.Age and 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Key words
milnacipran/population pharmacokinetics/high performance liquid chromatography-mass spectrum/mass spectrum分类
医药卫生引用本文复制引用
阮灿军,赵立波,果伟,李文标,董芳,翟屹民,王传跃..盐酸米那普仑在中国健康人体中的群体药代动力学研究[J].中国临床药理学杂志,2017,33(4):323-326,4.基金项目
首都卫生发展专项基金资助项目(2014-2-2122) （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) （z15110000401580）
北京市医院管理局临床医学发展专项基金资助项目(ZYLX201403) （ZYLX201403）
