| http://purl.uniprot.org/citations/18314419 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18314419 | http://www.w3.org/2000/01/rdf-schema#comment | "ObjectiveThe uptake of drugs into hepatocytes is a key determinant for hepatic metabolism, intrahepatic action, their subsequent systemic plasma concentrations, and extrahepatic actions. In vitro and in vivo studies indicate that many drugs used for treatment of cardiovascular diseases (e.g., oral antidiabetic drugs, statins) are taken up into hepatocytes by distinct organic anion transporters (organic anion transporting polypeptides [OATPs]; gene symbol SLCO/SLC21) or organic cation transporters (OCTs; gene symbol SLC22). Because most patients with type 2 diabetes receive more than one drug and inhibition of drug transporters has been recognized as a new mechanism underlying drug-drug interactions, we tested the hypothesis of whether oral antidiabetic drugs can inhibit the transport mediated by hepatic uptake transporters.Research design and methodsUsing stably transfected cell systems recombinantly expressing the uptake transporters OATP1B1, OATP1B3, OATP2B1, or OCT1, we analyzed whether the antidiabetic drugs repaglinide, rosiglitazone, or metformin influence the transport of substrates and drugs (for OATPs, sulfobromophthalein [BSP] and pravastatin; for OCT1, 1-methyl-4-phenylpyridinium [MPP(+)] and metformin).ResultsMetformin did not inhibit the uptake of OATP and OCT1 substrates. However, OATP-mediated BSP and pravastatin uptake and OCT1-mediated MPP(+) and metformin uptake were significantly inhibited by repaglinide (half-maximal inhibitory concentration [IC(50)] 1.6-5.6 micromol/l) and rosiglitazone (IC(50) 5.2-30.4 micromol/l).ConclusionsThese in vitro results demonstrate that alterations of uptake transporter function by oral antidiabetic drugs have to be considered as potential mechanisms underlying drug-drug interactions."xsd:string |
| http://purl.uniprot.org/citations/18314419 | http://purl.org/dc/terms/identifier | "doi:10.2337/db07-1515"xsd:string |
| http://purl.uniprot.org/citations/18314419 | http://purl.uniprot.org/core/author | "Glaeser H."xsd:string |
| http://purl.uniprot.org/citations/18314419 | http://purl.uniprot.org/core/author | "Fromm M.F."xsd:string |
| http://purl.uniprot.org/citations/18314419 | http://purl.uniprot.org/core/author | "Konig J."xsd:string |
| http://purl.uniprot.org/citations/18314419 | http://purl.uniprot.org/core/author | "Bachmakov I."xsd:string |
| http://purl.uniprot.org/citations/18314419 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18314419 | http://purl.uniprot.org/core/name | "Diabetes"xsd:string |
| http://purl.uniprot.org/citations/18314419 | http://purl.uniprot.org/core/pages | "1463-1469"xsd:string |
| http://purl.uniprot.org/citations/18314419 | http://purl.uniprot.org/core/title | "Interaction of oral antidiabetic drugs with hepatic uptake transporters: focus on organic anion transporting polypeptides and organic cation transporter 1."xsd:string |
| http://purl.uniprot.org/citations/18314419 | http://purl.uniprot.org/core/volume | "57"xsd:string |
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