Tran Hieu X, Herrington Jon D
Department of Pharmacy, Baylor University Medical Center, Baylor Scott & White Health, Dallas, Texas, USA.
Department of Pharmacy, Scott & White Memorial Hospital, Baylor Scott & White Health, Temple, Texas, USA Department of Medicine, Health Science Center, Texas A&M University, Temple, Texas, USA
J Oncol Pharm Pract. 2016 Dec;22(6):801-805. doi: 10.1177/1078155215608524. Epub 2015 Sep 28.
Numerous drug interactions with methotrexate have been identified, which can lead to serious life-threatening effects. Up to 90% of methotrexate is excreted unchanged in the urine with primary excretion dependent on organic anion transport in the renal proximal tubule. The two pathways responsible for methotrexate secretion are organic anion transport 1 and primarily organic anion transport 3. Penicillins undergo tubular secretion via organic anion transport, and cephalosporins are believed to also possess a similar risk when administered with methotrexate; however, there are no human studies observing this interaction with cephalosporins and methotrexate. Ceftriaxone undergoes biliary clearance and has low affinity for the same organic anion transports as methotrexate; therefore, ceftriaxone has a low potential to interact with methotrexate. Cefepime is primarily secreted by organic cation transport N2, and also has a low potential to interact with methotrexate. This case report describes the pharmacokinetic effect of concomitant beta-lactam therapy in a patient receiving high-dose methotrexate.
已发现许多与甲氨蝶呤的药物相互作用，这可能导致严重的危及生命的后果。高达90%的甲氨蝶呤以原形经尿液排泄，主要排泄取决于肾近端小管中的有机阴离子转运。负责甲氨蝶呤分泌的两条途径是有机阴离子转运体1和主要是有机阴离子转运体3。青霉素通过有机阴离子转运进行肾小管分泌，并且据信头孢菌素与甲氨蝶呤合用时也具有类似风险；然而，尚无人体研究观察到头孢菌素与甲氨蝶呤之间的这种相互作用。头孢曲松经胆汁清除，对与甲氨蝶呤相同的有机阴离子转运体亲和力低；因此，头孢曲松与甲氨蝶呤相互作用的可能性低。头孢吡肟主要通过有机阳离子转运体N2分泌，与甲氨蝶呤相互作用的可能性也低。本病例报告描述了在接受高剂量甲氨蝶呤治疗的患者中联合使用β-内酰胺类药物治疗的药代动力学效应。
