Lafforgue P, Monjanel-Mouterde S, Durand A, Catalin J, Acquaviva P C
Department of Rheumatology, Timone Hospital, Marseilles, France.
J Rheumatol. 1993 Feb;20(2):263-7.
A study of methotrexate (MTX) pharmacokinetics with and without prednisolone was performed in 33 patients with rheumatoid arthritis. Ten mg im MTX were given on Day 0; patients were divided into 3 groups of 11 persons: Group 1: no corticosteroid; Group 2: prednisolone 15 mg/day per os from D -3 on; Group 3: patients continuing longterm prednisolone treatment (15 mg/day). Groups 1 and 2 were randomized. MTX plasma concentrations were measured at T 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12 and 24 h using fluorescence polarization immunoassay (TDx Abbott). There was no difference between MTX pharmacokinetics of Groups 1 and 2. Area under the curve (AUC), Cmax and residual concentration at 24th h were higher, while total body and renal MTX clearances were lower in Group 3 vs Groups 1 and 2. Only the differences in AUC and total clearance were significant (p < 0.01 and p < 0.05). Tmax and terminal half-life did not differ. Our data suggest a possible influence of prednisolone on MTX pharmacokinetics in longstanding steroid treated patients. The pharmacological processes that might be involved are discussed.
对33例类风湿性关节炎患者进行了一项关于甲氨蝶呤（MTX）在联用和不联用泼尼松龙情况下药代动力学的研究。第0天给予10mg甲氨蝶呤肌肉注射；患者被分为3组，每组11人：第1组：不使用皮质类固醇；第2组：从第 -3天起口服泼尼松龙15mg/天；第3组：继续长期泼尼松龙治疗（15mg/天）。第1组和第2组为随机分组。使用荧光偏振免疫分析法（雅培TDx）在T 0、0.25、0.5、0.75、1、2、4、6、8、12和24小时测量甲氨蝶呤血浆浓度。第1组和第2组的甲氨蝶呤药代动力学无差异。与第1组和第2组相比，第3组的曲线下面积（AUC）、Cmax和第24小时的残留浓度较高，而甲氨蝶呤的全身清除率和肾清除率较低。仅AUC和总清除率的差异具有统计学意义（p < 0.01和p < 0.05）。达峰时间（Tmax）和末端半衰期无差异。我们的数据表明，泼尼松龙可能对长期接受类固醇治疗的患者的甲氨蝶呤药代动力学有影响。文中讨论了可能涉及的药理过程。
