Lafforgue P, Monjanel-Mouterde S, Durand A, Catalin J, Acquaviva P C
Department of Rheumatology, Timone Hospital, Marseilles, France.
J Rheumatol. 1995 May;22(5):844-9.
To determine if the variability in the efficacy of methotrexate (MTX) in rheumatoid arthritis (RA) is correlated with its pharmacokinetics.
MTX pharmacokinetics was evaluated in 46 patients with RA starting a weekly intramuscular low dose MTX treatment. The patients were divided into 32 responders and 14 nonresponders to MTX according to the clinical response in the 6 months after the pharmacokinetic study. MTX plasma (at T0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12 and 24 h) and urine concentrations were measured with the TDx Abbott fluorescence polarization immunoassay.
The MTX dosage, age, sex, RA duration, hepatic and renal functions of responders and nonresponders were not different. No difference was found either in peak concentration, residual 24th hour concentration, area under the curve, total body clearance, renal clearance, and terminal T1/2 life of MTX in responders and nonresponders. Surprisingly, patients with adverse reactions had higher total body and renal MTX clearances than those without side effects during the study.
These data suggest that plasma MTX measurements are not helpful in defining an optimal treatment regimen.
确定甲氨蝶呤（MTX）治疗类风湿关节炎（RA）疗效的变异性是否与其药代动力学相关。
对46例开始每周一次低剂量肌肉注射MTX治疗的RA患者进行MTX药代动力学评估。根据药代动力学研究后6个月的临床反应，将患者分为MTX治疗反应者32例和无反应者14例。采用雅培TDx荧光偏振免疫分析法测定MTX血浆浓度（在T0、0.25、0.5、0.75、1、2、4、6、8、12和24小时）和尿液浓度。
反应者和无反应者的MTX剂量、年龄、性别、RA病程、肝肾功能无差异。反应者和无反应者在MTX的峰浓度、第24小时残留浓度、曲线下面积、总体清除率、肾清除率和终末T1/2半衰期方面均未发现差异。令人惊讶的是，在研究期间，有不良反应的患者比无副作用的患者具有更高的MTX总体清除率和肾清除率。
这些数据表明，血浆MTX测定对确定最佳治疗方案并无帮助。
