Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid arthritis therapy.

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Inoue K, Yuasa H

Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid arthritis therapy.

Drug Metab Pharmacokinet. 2014;29(1):12-9. Epub 2013 Nov 26.

PubMed ID

24284432 [ View in PubMed

]

Abstract

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.

DrugBank Data that Cites this Article

Drugs

Methotrexate

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Methotrexate	Bifunctional purine biosynthesis protein PURH	Protein	Humans	Yes	Inhibitor	Details
Methotrexate	Dihydrofolate reductase	Protein	Humans	Yes	Inhibitor	Details
Methotrexate	Thymidylate synthase	Protein	Humans	Yes	Inhibitor	Details

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Methotrexate	Folate receptor beta	Protein	Humans	Unknown	Substrate	Details
Methotrexate	Proton-coupled amino acid transporter 1	Protein	Humans	Unknown	Substrate	Details
Methotrexate	Solute carrier family 15 member 1	Protein	Humans	Unknown	Substrate	Details