类风湿性关节炎患者甲氨喋呤的群体药代动力学

The Population Pharmacokinetics of Methotrexate in Rheumatoid Arthritis

目的：研究类风湿性关节炎患者甲氨喋呤的群体药代动力学。方法：收集风湿科４０例类风湿性关节炎（ＲＡ）患者单剂量口服甲氨喋呤（ＭＴＸ）稀疏血药浓度数据１５５个，采用荧光偏振免疫法（ＦＰＩＡ）测定，按口服一级吸收二房室线性开放型模型，用ＮＯＮＭＥＭ程序估算甲氨喋呤的群体药代动力学参数，并定量分析患者年龄、性别、族别、体重、肌酐清除率等固定效应对甲氨喋呤清除率的影响，得到最终回归模型。结果：肌酐清除率对甲氨喋呤清除率具有显著影响（Ｐ＜０．０５）ＣＬ（Ｌ·ｈ－１）＝６．５３＋０．０１８４＊ＣＬｅｒ。甲氨喋呤药代动力学参数个体化差异较大，各参数群体标准值及变异分别是：Ｈａ为１．６９ｈ－１（８１％）；Ｖｃ为２９．７１（２５％）；Ｖｐ为８．１９１（１１０％）；Ｌａｇ为２２．０６ｍｉｎ（２６％）；Ｑ为１．１６１ｈ－１（４７０％）；固定效应参数θＣＬｅｒ＇０．３０７。结论：此研究结果有助于甲氨喋呤合理应用。

OBJECTIVE: The population pharmacokinetics ofmethotrexate(MTX) was evaluated using 155serum concentrations of methotrexate administrated by oral from 40 rheumatoid arthritis(RA) patients with NONMEM program. METHODS:The concentrations of MTX in serum were determined by fluorescence polarization immunoassay (FPIA). A 2- compartment -open pharmacokinetic model with first-order absorption and first-order elimination was used. The effects of a variety of factors on the clearance of methotrexate were investigated. The fixed factor that significantly (P<0.05) influenced the clearance of methotrexate was creatinine clearance (CCR,L·h-1). RESULTS:The final model in this study clearance (CL,L·h-1)=6.53+0.0184*CLer. Pharmacokinetic parameters(RSD%)in this study CL were,6.531h-1(37%); Ka werel .69h-1(81%); Vc were29.71(25%); Vp were8. 191 (110%);Lag were22.06min(26%), owers 1. 161h-1(470%); fixed parameter θCLer' 0.307.CONCLUSION:These results may be helpful to a rational individulized methodtrexate dosage regimen.