Seideman P, Albertioni F, Beck O, Eksborg S, Peterson C
Danderyd Hospital, Stockholm, Sweden.
Arthritis Rheum. 1994 Jun;37(6):830-3. doi: 10.1002/art.1780370609.
To evaluate the effects of a single dose of chloroquine (CQ) on the pharmacokinetics of methotrexate (MTX) in patients with rheumatoid arthritis.
Eleven patients (ages 41-75 years) who were taking oral doses of MTX (15 mg/week) were studied after a dose of MTX alone and after a dose of MTX plus CQ (250 mg). Plasma and urine samples were collected for 24 hours after dose intake, and the concentrations of MTX and its major metabolite 7-hydroxymethotrexate were determined by high-performance liquid chromatography.
Administration of CQ together with MTX caused a reduction in the area under the plasma MTX concentration versus time curve (AUC). The median value of individual AUC ratios (MTX/MTX + CQ) was 1.6 (95% confidence interval 1.2-3.6).
The most likely mechanism for the interaction is that CQ reduces the bioavailability of MTX. This gives a possible explanation for a suggested reduction in MTX-associated liver toxicity by coadministration of CQ. The significance of the interaction for the therapeutic effect remains to be elucidated.
评估单剂量氯喹（CQ）对类风湿关节炎患者甲氨蝶呤（MTX）药代动力学的影响。
对11例口服MTX（15毫克/周）的患者（年龄41 - 75岁）进行研究，分别在单剂量服用MTX后以及服用MTX加CQ（250毫克）后进行观察。给药后24小时采集血浆和尿液样本，采用高效液相色谱法测定MTX及其主要代谢产物7 - 羟基甲氨蝶呤的浓度。
CQ与MTX联合给药导致血浆MTX浓度 - 时间曲线下面积（AUC）降低。个体AUC比值（MTX/MTX + CQ）的中位数为1.6（95%置信区间1.2 - 3.6）。
相互作用最可能的机制是CQ降低了MTX的生物利用度。这为联合使用CQ可降低MTX相关肝毒性的说法提供了一种可能的解释。这种相互作用对治疗效果的意义仍有待阐明。
