Population pharmacokinetics of milnacipran in Chinese healthy volunteers
10.13699/j.cnki.1001-6821.2017.04.010
- VernacularTitle:盐酸米那普仑在中国健康人体中的群体药代动力学研究
- Author:
Can-Jun RUAN
1
;
Li-Bo ZHAO
;
Wei GUO
;
Wen-Biao LI
;
Fang DONG
;
Yi-Min ZHAI
;
Chuan-Yue WANG
Author Information
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
- Keywords:
milnacipran;
population pharmacokinetics;
high performance liquid chromatography-mass spectrum/mass spectrum
- From:
The Chinese Journal of Clinical Pharmacology
2017;33(4):323-326
- CountryChina
- Language:Chinese
-
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.
