Interaction between methotrexate and nonsteroidal anti-inflammatory drugs in organic anion transporter.
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Uwai Y, Saito H, Inui K
Interaction between methotrexate and nonsteroidal anti-inflammatory drugs in organic anion transporter.
Eur J Pharmacol. 2000 Dec 1;409(1):31-6.
- PubMed ID
- 11099697 [ View in PubMed]
- Abstract
The antifolate drug methotrexate is mainly eliminated from the body by renal tubular secretion via organic anion transporters. In clinical situations, severe methotrexate toxicity, due to an increase in serum concentrations, was observed after coadministration with nonsteroidal anti-inflammatory drugs (NSAIDs) or probenecid. In this study, we examined the effects of NSAIDs and probenecid on methotrexate transport via the rat renal organic anion transporter rOAT1, using Xenopus laevis oocytes. [3H]Methotrexate uptake was markedly stimulated in the rOAT1 cRNA-injected oocytes, and this uptake was inhibited by probenecid and various NSAIDs, whereas the influence of salicylate was less. The Dixon plots showed that probenecid, indomethacin and salicylate competitively inhibited rOAT1 with apparent K(i) values of 15.8 microM, 4.2 microM and 1.0 mM, respectively. These findings demonstrate that rOAT1 is the major site of the transporter-mediated interaction between methotrexate and NSAIDs and/or probenecid, leading to a decrease in renal excretion of methotrexate.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Dexibuprofen Solute carrier family 22 member 6 Protein Humans UnknownNot Available Details Flufenamic acid Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails Ibuprofen Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails Indomethacin Solute carrier family 22 member 6 Protein Humans UnknownSubstrateInhibitorDetails Ketoprofen Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails Phenylbutazone Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails Probenecid Solute carrier family 22 member 6 Protein Humans UnknownSubstrateInhibitorDetails Salicylic acid Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails