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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 model of citalopram (CIT) in healthy male volunteers in China and evaluate the bioequivalence of CIT by comparing PPK model with non-compartmental (NCA) model. Methods: Twenty-three healthy male volunteers were enrolled in this study. Blood samples were taken from 0 to 144 hours after CIT. Plasma concentrations of CIT were analyzed by high performance liquid chromatography-electrospray ionization tandem mass spectrometry. Non-linear mixed-effects model (NONMEM) Model, and evaluate the bioequivalence of CIT using NAC model method and PPK model method. RESULTS: The PPK model of CIT fitted a one-compartment model and estimated CIT clearance and volume distribution were (15.90 ± 0.70) L / h and (702.0 ± 19.2) L, respectively. The 90% confidence interval of relative bioavailability estimated by NCA and PPK models was 96.4% -105.4% and 92.5% -103.4%, respectively, reaching the bioequivalence criterion. Conclusion: The NONMEM method can be used to evaluate the bioequivalence of CIT.