Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences.
Drug Metab Pharmacokinet. 2014;29(1):12-9. doi: 10.2133/dmpk.dmpk-13-rv-119. Epub 2013 Nov 26.
Methotrexate (MTX) is a derivative of folic acid (folate) and commonly used as an anchor drug for the treatment of rheumatoid arthritis (RA). The pharmacokinetics (PK) and pharmacodynamics (PD) of MTX entirely depends on the function of specific transporters that belong to the two major superfamilies, solute carrier transporters and ATP-binding cassette transporters. Several transporters have been identified as being able to mediate the transport of MTX, and suggested to be involved in the disposition in the body and in the regulation of intracellular metabolism in target cells, together with several enzymes involved in folate metabolism. Thus, drug-drug interactions through the transporters and their genetic polymorphisms may alter the PK and PD of MTX, resulting in an interpatient variability of efficacy. This review summarizes the PK and PD of MTX, particularly in relation to RA therapy and focuses on the roles of transporters involved in PK and PD with the aim of facilitating an understanding of the molecular basis of the mechanism of MTX action to achieve its effective use in RA therapy.
甲氨蝶呤（MTX）是叶酸（叶酸）的衍生物，通常用作治疗类风湿关节炎（RA）的锚定药物。MTX 的药代动力学（PK）和药效动力学（PD）完全取决于属于两个主要超家族的特定转运体的功能，即溶质载体转运体和 ATP 结合盒转运体。已经确定了几种转运体能够介导 MTX 的转运，并认为它们参与了体内的处置以及靶细胞内代谢的调节，同时还涉及几种参与叶酸代谢的酶。因此，通过转运体及其遗传多态性的药物-药物相互作用可能会改变 MTX 的 PK 和 PD，导致疗效的个体间差异。本综述总结了 MTX 的 PK 和 PD，特别是与 RA 治疗有关的 PK 和 PD，并重点介绍了参与 PK 和 PD 的转运体的作用，旨在帮助理解 MTX 作用机制的分子基础，以实现其在 RA 治疗中的有效应用。
