The key role of organic anion transporter 3 in the drug-drug interaction between tranilast and methotrexate.

Abstract

Tranilast, N-(3',4'-dimethoxycinnamoyl)-anthranilic acid, is an anti-allergic drug and is considered for use in the treatment of rheumatoid arthritis. Methotrexate, an antimetabolite and folate antagonist to treat some cancers, is also a first-line drug for RA. The aim of this study was to understand whether tranilast could inhibit renal uptake transporters (Oat1, Oat3, and Oct2) and whether MTX combined with TL would have drug-drug interactions. The results of kidney slices and HEK293T-OAT3 cell uptake experiments showed that TL (10 μM) could inhibit the uptake of penicillin G and MTX, which are substrates of OAT3. When TL (10 mg/kg) was combined with MTX (5 mg/kg), the area under the curve and peak concentration of MTX increased by 46.46% and 113.51%, respectively, while the pharmacokinetic process of tranilast (10 mg/kg) was not changed by methotrexate (5 mg/kg). TL could increase plasma exposure of MTX by inhibiting Oat3 in vitro and in vivo.

• Authors: Jingjing Wang, Wenjing Yuan, Qingqing Shen, Qipeng Wu, Zhenzhou Jiang, Wei Wu, Luyong Zhang, Xin Huang
• Journal: Journal of biochemical and molecular toxicology (J Biochem Mol Toxicol) Vol. 36 Issue 4 Pg. e22983 (Apr 2022) ISSN: 1099-0461 [Electronic] United States
• PMID: 35019195 (Publication Type: Journal Article)
• Copyright: © 2022 Wiley Periodicals LLC.

Chemical References

• Organic Anion Transport Protein 1
• Organic Anion Transporters, Sodium-Independent
• ortho-Aminobenzoates
• tranilast
• Methotrexate

Topics

• Drug Interactions
• HEK293 Cells
• Humans
• Kidney
• Methotrexate (pharmacology)
• Organic Anion Transport Protein 1
• Organic Anion Transporters, Sodium-Independent
• ortho-Aminobenzoates