As an active transporter of anionic molecules in the kidney, OAT3 plays a role in the renal elimination of many drugs and is also thought to be involved in drug-drug interactions in the kidney. A number of drugs have been identified as substrates or inhibitors of OAT3 including several non-steroidal anti-inflammatory drugs (NSAIDs) and various antibiotics. To date, most studies of drug interactions with OAT3 have focused on a few compounds or at most, a small panel of structural analogs. The goal of the current study was to identify FDA approved drugs that interact with OAT3 using a high-throughput screening approach. A library of 937 FDA approved drugs was screened using a cell-based fluorescence assay. A total of 55 drugs were identified as hits including NSAIDS, anti-diabetic agents, and macrolide antibiotics not previously known to interact with OAT3. Kinetics profiles were generated for a selection of drugs as validation for the screen.
|Advisor:||Giacomini, Kathy M.|
|Commitee:||Giacomini, Kathy M., Kroetz, Deanna L., Kwok, Pui Y.|
|School:||University of California, San Francisco|
|Department:||Pharmaceutical Sciences and Pharmacogenomics|
|School Location:||United States -- California|
|Source:||MAI 47/06M, Masters Abstracts International|
|Keywords:||Drug drug interaction, Membrane transporters, OAT3, Screen|
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