The aim was to investigate if the pharmacokinetics of methotrexate (MTX) are affected by the addition of cyclosporin (CsA). Forty patients diagnosed with early rheumatoid arthritis (RA) were included in this open prospective study: 20 patients were treated with a dose of 7.5 mg MTX and a dose of 2.5 mg/kg CsA, 20 patients were treated with a dose of 7.5 mg MTX and placebo. Baseline measurements of plasma MTX and erythrocyte MTX were made. Area under the plasma concentration versus time curve (AUC) and other pharmacokinetic variables were estimated by means of a population based software model. Clinical improvement of 20–50–70% according to the American College of Rheumatology (ACR) and adverse events were evaluated ongoing for 52 weeks. We found that mean peak plasma MTX concentration was significantly higher in the MTX + CsA combination treatment group (p = .003). No differences in AUC, erythrocyte MTX or other pharmacokinetic parameters were found between the two treatment groups. Estimated Glomerular Filtration Rate (eGFR) decreased significantly in the MTX + CsA treatment group (p < .001), but no serious adverse events occurred in either of the two groups. In conclusion, CsA added to methotrexate treatment in early RA significantly increased peak-plasma MTX concentration, but other pharmacokinetic parameters and measurements of MTX were unchanged.

目的是研究甲氨蝶呤（MTX）的药代动力学是否受环孢菌素（CsA）的影响。这项开放的前瞻性研究包括40名被诊断为早期类风湿关节炎（RA）的患者：20例患者接受7.5 mg MTX剂量和2.5 mg / kg CsA剂量治疗，20例患者接受7.5 mg MTX剂量治疗和安慰剂。对血浆MTX和红细胞MTX进行基线测量。血浆浓度-时间曲线下面积（AUC）和其他药代动力学变量是通过基于人群的软件模型估算的。根据美国风湿病学会（ACR）的临床改善20％至50％至70％，不良事件持续52周进行了评估。p = .003）。在两个治疗组之间未发现AUC，红细胞MTX或其他药代动力学参数的差异。MTX + CsA治疗组的估计肾小球滤过率（eGFR）显着降低（p <.001），但两组均未发生严重的不良事件。总之，在RA早期，在甲氨蝶呤治疗中加入CsA会显着增加血浆血浆MTX的峰值浓度，但其他药代动力学参数和MTX的测定均未改变。