Biomaterial Database

Interaction between methotrexate and nonsteroidal anti-inflammatory drugs in organic anion transporter. 2000

Y Uwai, and H Saito, and K Inui

Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Sakyo, Japan.

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.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008727	Methotrexate	An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.	Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D009865	Oocytes	Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).	Ovocytes,Oocyte,Ovocyte
D011339	Probenecid	The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy.	Benecid,Benemid,Benuryl,Pro-Cid,Probecid,Probenecid Weimer
D002352	Carrier Proteins	Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes.	Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000894	Anti-Inflammatory Agents, Non-Steroidal	Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.	Analgesics, Anti-Inflammatory,Aspirin-Like Agent,Aspirin-Like Agents,NSAID,Non-Steroidal Anti-Inflammatory Agent,Non-Steroidal Anti-Inflammatory Agents,Nonsteroidal Anti-Inflammatory Agent,Anti Inflammatory Agents, Nonsteroidal,Antiinflammatory Agents, Non Steroidal,Antiinflammatory Agents, Nonsteroidal,NSAIDs,Nonsteroidal Anti-Inflammatory Agents,Agent, Aspirin-Like,Agent, Non-Steroidal Anti-Inflammatory,Agent, Nonsteroidal Anti-Inflammatory,Anti-Inflammatory Agent, Non-Steroidal,Anti-Inflammatory Agent, Nonsteroidal,Anti-Inflammatory Analgesics,Aspirin Like Agent,Aspirin Like Agents,Non Steroidal Anti Inflammatory Agent,Non Steroidal Anti Inflammatory Agents,Nonsteroidal Anti Inflammatory Agent,Nonsteroidal Anti Inflammatory Agents,Nonsteroidal Antiinflammatory Agents
D000964	Antimetabolites, Antineoplastic	Antimetabolites that are useful in cancer chemotherapy.	Antineoplastic Antimetabolites
D014528	Uricosuric Agents	Gout suppressants that act directly on the renal tubule to increase the excretion of uric acid, thus reducing its concentrations in plasma.	Uricosuric Agent,Agent, Uricosuric,Agents, Uricosuric
D014982	Xenopus laevis	The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.	Platanna,X. laevis,Platannas,X. laevi