群体药动学模型估算我国健康男性西酞普兰生物等效性

Assessment of bioequivalence of citalopram in healthy Chinese subjects by population pharmacokinetic model

目的:建立我国健康男性志愿者服用西酞普兰(CIT)的群体药动学(PPK)模型,并比较PPK模型与非房室(NCA)模型法估算CIT生物等效性的价值。方法:23名健康男性志愿者服用CIT后采集0～144h血标本,采用高效液相色谱-电喷雾串联质谱法分析血浆中的CIT浓度,采用非线性混合效应模型(NONMEM)法评估CIT的PPK模型,并用NAC模型法和PPK模型法评价CIT的生物等效性。结果:CIT的PPK模型符合一房室模型,估算的CIT清除率和分布容积分别为(15.90±0.70)L/h和(702.0±19.2)L。采用NCA和PPK模型估算的CIT相对生物利用度90%可信区间分别为96.4%～105.4%和92.5%～103.4%,达到生物等效性的标准。结论:NONMEM法可用于评价CIT的生物等效性。

Objective To establish a population pharmacokinetic（PPK） model of citalopram（CIT） in healthy man Chinese subjects,and to compare the bioequivalence of CIT estimated by PPK with that estimated by non-compartmental （NCA） model.Methods Blood samples of 23 healthy subjects were collected after CIT was given,and samples were analyzed using liquid chromatography-mass spectrometry.The PPK model of CIT was evaluated by nonlinear mixed-effect modeling（NONMEM）.Bioequivalence of CIT was evaluated by both PPK and NCA method.Results The PPK model of CIT was consistent with one-compartment model.The estimated CIT clearance rate was（15.90±0.70） L/h and volume of distribution was（702.0±19.2） L.The CIT bioavailability estimated by NCA and PPK model was 90%,and the confidence intervals were 96.4%～105.4%and 92.5%～103.4%,respectively.Conclusions Bioequivalence of CIT could be estimated by NONMEM model.