Quantitative Evaluation of the Drug-Drug Interactions between Methotrexate and Nonsteroidal Anti-Inflammatory Drugs in the Renal Uptake Process Based on the Contribution of Organic Anion Transporters and Reduced Folate Carrier

2004 ◽  
Vol 309 (1) ◽  
pp. 226-234 ◽  
Author(s):  
Yoshitane Nozaki ◽  
Hiroyuki Kusuhara ◽  
Hitoshi Endou ◽  
Yuichi Sugiyama
Keyword(s):  
Drug Interactions ◽  
Quantitative Evaluation ◽  
Organic Anion ◽  
Reduced Folate Carrier ◽  
Organic Anion Transporters ◽  
Renal Uptake ◽  
Anion Transporters ◽  
Uptake Process ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Inhibition of methotrexate uptake by glucuronides of nonsteroidal anti-inflammatory drugs via organic anion transporters OAT1 and OAT3

2017 ◽  
Vol 32 (1) ◽  
pp. S51
Author(s):  
Masahiro Iwaki ◽  
Yuri Irino ◽  
Manami Take ◽  
Sachiko Egashira
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporters ◽  
Anion Transporters ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

scholarly journals Evaluation of para-Aminosalicylic Acid as a Substrate of Multiple Solute Carrier Uptake Transporters and Possible Drug Interactions with Nonsteroidal Anti-inflammatory Drugs In Vitro

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
M. Masud Parvez ◽  
Ho Jung Shin ◽  
Jin Ah Jung ◽  
Jae-Gook Shin
Keyword(s):  
Drug Interactions ◽  
Organic Anion ◽  
Multidrug Resistant ◽  
Aminosalicylic Acid ◽  
Anion Transporters ◽  
Net Uptake ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

ABSTRACT para-Aminosalicylic acid (PAS) is a second-line antituberculosis drug that has been used to treat multidrug-resistant and extensively drug-resistant tuberculosis for more than 60 years. Renal secretion and glomerular filtration are the major pathways for the elimination of PAS. We comprehensively studied PAS transport by using cell lines that overexpressed various transporters and found that PAS acts as a novel substrate of an organic anionic polypeptide (OATP1B1), organic cationic transporters (OCT1 and OCT2), and organic anion transporters (OAT1 and OAT3) but is not a substrate of any ATP-binding cassette (ABC) transporters. Net PAS uptake was measured, and the transport affinities (Km values) for OATP1B1, OCT1, OCT2, OAT1, and OAT3 were found to be 50.0, 20.3, 28.7, 78.1, and 100.1 μM, respectively. The net uptake rates suggested that renal OAT1 and OAT3 play relatively major roles in PAS elimination. The representative inhibitors rifampin for OATP1B1, probenecid for OAT1 and OAT3, and verapamil for OCT1 and OCT2 greatly inhibited PAS uptake, suggesting that PAS is dependent on multiple transporters for uptake. We also evaluated nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), and metformin for the inhibition of PAS uptake via these transporters. Half-maximal (50%) inhibitory concentrations (IC50s) were kinetically determined and used to predict the drug-drug interactions (DDIs) affecting these transporters' activity toward PAS. We found that rifampin, probenecid, ibuprofen, naproxen, cimetidine, and quinidine each exhibited a significant potential for in vivo DDIs with PAS. In this study, PAS was found to be a novel substrate of several transporters, and drugs that inhibit these transporters can reduce PAS elimination.

scholarly journals Inhibition of Methotrexate Uptake via Organic Anion Transporters OAT1 and OAT3 by Glucuronides of Nonsteroidal Anti-inflammatory Drugs

2017 ◽  
Vol 40 (6) ◽  
pp. 926-931 ◽  
Author(s):  
Masahiro Iwaki ◽  
Hiroaki Shimada ◽  
Yuri Irino ◽  
Manami Take ◽  
Sachiko Egashira
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporters ◽  
Anion Transporters ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Interactions of Human Organic Anion Transporters and Human Organic Cation Transporters with Nonsteroidal Anti-Inflammatory Drugs

2002 ◽  
Vol 303 (2) ◽  
pp. 534-539 ◽  
Author(s):  
Suparat Khamdang ◽  
Michio Takeda ◽  
Rie Noshiro ◽  
Shinichi Narikawa ◽  
Atsushi Enomoto ◽  
...  
Keyword(s):  
Organic Cation ◽  
Organic Anion ◽  
Organic Anion Transporters ◽  
Organic Cation Transporters ◽  
Anion Transporters ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Cation Transporters

Renal organic anion transporters in drug–drug interactions and diseases

2018 ◽  
Vol 112 ◽  
pp. 8-19 ◽  
Author(s):  
Xiaokui Huo ◽  
Kexin Liu
Keyword(s):  
Drug Interactions ◽  
Organic Anion ◽  
Organic Anion Transporters ◽  
Anion Transporters

Renal Uptake of Substrates for Organic Anion Transporters Oat1 and Oat3 and Organic Cation Transporters Oct1 and Oct2 is Altered in Rats with Adenine-Induced Chronic Renal Failure

2013 ◽  
Vol 102 (3) ◽  
pp. 1086-1094 ◽  
Author(s):  
Hiroki Komazawa ◽  
Hiroaki Yamaguchi ◽  
Kazuhiro Hidaka ◽  
Jiro Ogura ◽  
Masaki Kobayashi ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Organic Cation ◽  
Organic Anion ◽  
Organic Anion Transporters ◽  
Organic Cation Transporters ◽  
Renal Uptake ◽  
Anion Transporters ◽  
Cation Transporters

The Contribution of Organic Anion Transporters OAT1 and OAT3 to the Renal Uptake of Rosuvastatin

2007 ◽  
Vol 322 (3) ◽  
pp. 1221-1227 ◽  
Author(s):  
A. S. Windass ◽  
S. Lowes ◽  
Y. Wang ◽  
C. D. A. Brown
Keyword(s):  
Organic Anion ◽  
Organic Anion Transporters ◽  
Renal Uptake ◽  
Anion Transporters

Potent Inhibitors of Organic Anion Transporters 1 and 3 From Natural Compounds and Their Protective Effect on Aristolochic Acid Nephropathy

2020 ◽  
Vol 175 (2) ◽  
pp. 279-291
Author(s):  
Caiyu Li ◽  
Xue Wang ◽  
Yajuan Bi ◽  
Heshui Yu ◽  
Jing Wei ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Natural Compound ◽  
Aristolochic Acid ◽  
Organic Anion ◽  
Critical Role ◽  
Natural Compounds ◽  
Organic Anion Transporters ◽  
Herbal Products ◽  
Anion Transporters

Abstract Organic anion transporters 1 and 3 (OAT1 and OAT3) play a critical role in renal drug-drug interactions and are involved in the nephrotoxicity of many anionic xenobiotics. To date, relatively little is known about the interaction of natural compounds with OAT1 and OAT3. Of the 270 natural compounds screened in the present study, 21 compounds inhibited OAT1 and 45 compounds inhibited OAT3. Further concentration-dependent studies identified 7 OAT1 inhibitors and 10 OAT3 inhibitors with IC50 values of <10 μM, and most of them were flavonoids, the most commonly ingested polyphenolic compounds in the diet and herbal products. Computational modeling of OAT1 and OAT3 revealed the important residues for the recognition of inhibitors. The two strong OAT inhibitors, namely wedelolactone and wogonin, were evaluated for their in vivo interactions with the OAT substrate aristolochic acid I (AAI), a natural compound causing aristolochic acid-induced nephropathy (AAN) in many species. The cytotoxicity of AAI increased in two OAT-overexpressing cell lines, with more cytotoxicity in OAT1-overexpressing cells, suggesting a more important role of OAT1 than OAT3 in AAN. Both wedelolactone and wogonin markedly increased serum AAI concentrations in AAI-treated rats and ameliorated kidney injuries in AAI-treated mice. To conclude, the present findings are of significant value in understanding natural compound-drug interactions and provide a natural source for developing treatments for AAN.

Species differences of organic anion transporters involved in the renal uptake of 4-amino-3-chlorophenyl hydrogen sulfate, a metabolite of resatorvid, between rats and dogs

2013 ◽  
Vol 34 (4) ◽  
pp. 236-246
Author(s):  
Toshiyuki Takeuchi ◽  
Fumihiro Jinno ◽  
Takuya Ebihara ◽  
Yuu Moriya ◽  
Rie Kadotani ◽  
...  
Keyword(s):  
Species Differences ◽  
Organic Anion ◽  
Organic Anion Transporters ◽  
Hydrogen Sulfate ◽  
Renal Uptake ◽  
Anion Transporters
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