银屑病患者甲氨蝶呤的群体药动学研究

目的:研究银屑病患者甲氨蝶呤(MTX)的群体药动学特征,为临床调整个体化用药提供新途径。方法:收集皮肤科50例银屑病患者单剂量静脉滴注MTX后稀疏血药浓度数据137个,采用荧光偏振免疫法(FPIA)测定,应用非线性混合效应模型(NONMEM)程序一步法估算MTX的群体药动学参数,并定量分析患者年龄、性别、体质量、肌酐清除率、尿素氮等因素对MTX药动学参数的影响。结果:按静脉滴注二房室线性开放模型估算的群体药动学参数中央室清除率(CL)、中央室表观分布容积(Vc)、外周室表观分布容积(Vp)及外周室清除率(Q)分别为10.4L·h-1、11.7L、6.61L及2.8L·h-1,其个体间变异ωCL、ωVc、ωVp、ωQ分别为16.8%、2.8%、11.7%及287.9%。且最终回归模型的MTX浓度估算值与实测值具有一致性。效应中尿素氮对Vp的影响具有显著意义(P>0.05),其协变量参数为(尿素氮/4)-0.845。结论:NONMEM法以二室模型群体参数估算的血药浓度值与实测值有良好相关性,此研究结果有助于MTX的临床合理应用。

Population Pharmacokinetics of Methotrexate in Patients with Psoriasis

OBJECTIVE： To study the characteristics of group pharmacokinetics of methotrexate （MTX） in patients with psoriasis so as to provide new approach for clinical adjustment of individualized medication. METHODS： 137 sparse serum concentration data of methopterin （MTX） were collected from 50 psoriasis patients following intravenous drip infusion with single dose of methopterin. The concentration of MTX was determined by fluorescence polarization immunoassay （FPIA）. The population pharmacokinetics of MTX was evaluated with NONMEM program and the effects of patients＇ age, sex, weight, creatinine clearance rate, blood urea nitrogen and other factors on MTX pharmacokinetic parameters were analyzed quantita- tively. RESULTS： Estimated in an intravenous drip infusion two - compartment linear open model, the population pharma- cokinetic parameters of MTX including CL, Vc, Vp and Q were 10.4 L·h^-1, 11.7 L, 6.61 L and 2.8 L·h^-1, respectively. The inter-individual variation of ωcL, ωve, ωvp and ωQ were 16.8%, 2.8%, 11.7% and 287.9%, respectively. The predicated concentration of MTZ in the final regression model was in accordance with the measured value. The effect of urea nitrogen on Vp was significant （P〉0.05） and its concomitant variable parameter was （BUN/4）^-0.845. CONCLUSION： The measured value of MTX concentration calculated using two - compartment linear open model by NONMEM program and the predicted values showed a good correlation. These results are conducive to clinical rational use of MTX.