Vakily Majid, Amer Fouad, Kukulka Michael J, Andhivarothai Nupun
Department of Drug Metabolism & Pharmacokinetics, TAP Pharmaceutical Products Inc., 675 North Field Drive, Lake Forest, IL 60045, USA.
J Clin Pharmacol. 2005 Oct;45(10):1179-86. doi: 10.1177/0091270005280100.
Drugs prescribed for rheumatoid arthritis are often associated with gastrointestinal toxicity, and proton pump inhibitors may be coadministered for gastroprotection. In this open-label study, the effect of lansoprazole 30 mg qd and naproxen 500 mg bid on the pharmacokinetic profile of methotrexate was investigated. Twenty-seven adult rheumatoid arthritis patients on stable oral methotrexate doses (7.5-15 mg/week) for a minimum of 3 months were enrolled. Methotrexate pharmacokinetics were assessed on days -1 (methotrexate alone) and 7 (methotrexate with lansoprazole and naproxen). Pharmacokinetics of methotrexate and 7-hydroxymethotrexate were not altered by coadministration of methotrexate with lansoprazole and naproxen; point estimates and 90% confidence intervals for the peak plasma concentration and area under the plasma concentration-time curve of methotrexate and 7-hydroxymethotrexate were within the 0.80 to 1.25 boundaries. Therefore, coadministration of naproxen and lansoprazole for 7 days does not affect the pharmacokinetic profile of low doses of methotrexate.
用于治疗类风湿性关节炎的药物通常会引发胃肠道毒性，因此可能会联合使用质子泵抑制剂来进行胃保护。在这项开放性研究中，研究了每日一次服用30毫克兰索拉唑和每日两次服用500毫克萘普生对甲氨蝶呤药代动力学特征的影响。招募了27名成年类风湿性关节炎患者，这些患者口服稳定剂量的甲氨蝶呤（7.5 - 15毫克/周）至少3个月。在第 -1天（单独服用甲氨蝶呤）和第7天（服用甲氨蝶呤与兰索拉唑和萘普生）评估甲氨蝶呤的药代动力学。甲氨蝶呤与兰索拉唑和萘普生联合使用并未改变甲氨蝶呤和7 - 羟基甲氨蝶呤的药代动力学；甲氨蝶呤和7 - 羟基甲氨蝶呤的血浆峰浓度和血浆浓度 - 时间曲线下面积的点估计值和90%置信区间在0.80至1.25范围内。因此，萘普生和兰索拉唑联合使用7天不会影响低剂量甲氨蝶呤的药代动力学特征。
