Dupuis L L, Koren G, Silverman E D, Laxer R M
Department of Pharmacy, Hospital for Sick Children, Toronto, Canada.
J Rheumatol. 1995 Aug;22(8):1570-3.
To determine the bioavailability of oral methotrexate (MTX) in patients with juvenile rheumatoid arthritis in the fasting and fed states.
Each patient randomly received their usual weekly MTX dose either orally (po) after an overnight fast, po immediately after a breakfast of their choice, or intravenously (iv) on 3 consecutive weeks. Blood samples were taken at 0, 0.5, 1, 1.5, 2, 3, 4, and 6 h after po and 0, 0.08, 0.25, 0.5, 1, 1.5, 2, 3, 4, and 6 h after iv administration.
Fourteen patients (10 female) aged 2.8 to 15.1 yrs completed the study; the results of 13 patients were evaluable. The mean elimination rate constant was 0.27 +/- 0.065, 0.26 +/- 0.067, and 0.25 +/- 0.11 h-1 after po fasting, po fed, and iv administration, respectively. The total area under the serum concentration vs time curve was 1.87 +/- 0.83, 1.50 +/- 0.51, and 1.85 +/- 0.80 mumol/l.h after po fasting, po fed, and iv administration, respectively. The maximum serum MTX concentration (Cmax) was 0.65 +/- 0.33 and 0.39 +/- 0.18 mumol/l after po fasting and po fed administration, respectively (p = 0.0022). The time to Cmax was 0.94 +/- 0.40 and 1.32 +/- 0.68 h after po fasting and po fed administration, respectively (p = 0.1464). The bioavailability of oral MTX while fasting was 1.1 +/- 0.51, while that after a meal was 0.88 +/- 0.35 (p = 0.0211).
These data indicate greater oral bioavailability of MTX in the fasting state. We recommend that children receive MTX on an empty stomach.
确定青少年类风湿关节炎患者在空腹和进食状态下口服甲氨蝶呤（MTX）的生物利用度。
每位患者连续3周随机接受其常规每周MTX剂量，分别在禁食过夜后口服（po）、选择早餐后立即口服或静脉注射（iv）。口服给药后0、0.5、1、1.5、2、3、4和6小时以及静脉给药后0、0.08、0.25、0.5、1、1.5、2、3、4和6小时采集血样。
14例年龄在2.8至15.1岁的患者（10例女性）完成了研究；13例患者的结果可评估。空腹口服、进食后口服和静脉给药后，平均消除速率常数分别为0.27±0.065、0.26±0.067和0.25±0.11 h⁻¹。空腹口服、进食后口服和静脉给药后，血清浓度-时间曲线下总面积分别为1.87±0.83、1.50±0.51和1.85±0.80 μmol/l·h。空腹口服和进食后口服给药后，血清MTX最高浓度（Cmax）分别为0.65±0.33和0.39±0.18 μmol/l（p = 0.0022）。空腹口服和进食后口服给药后达到Cmax的时间分别为0.94±0.40和1.32±0.68小时（p = 0.1464）。空腹时口服MTX的生物利用度为1.1±0.51，进食后为0.88±0.35（p = 0.0211）。
这些数据表明MTX在空腹状态下口服生物利用度更高。我们建议儿童空腹服用MTX。
