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Further exploration into the DDI between Gemfibrozil & Repaglinide in rats: Uptake Transporters

  • Published on September 27, 2017
  • Drug Drug Interactions (DDI)
  • Drug Transporters
  • Scientific Posters

Presented at ISSX 2017 Annula Meeting


Chase I. McCoy, Forrest A. Stanley, Chandra Kollu, Seema Muranjan, Krystal M. Green and Joanna E. Barbara


The clinically-relevant drug-drug interaction (DDI) between the dyslipidemia drug gemfibrozil and the antidiabetic repaglinide is well-documented throughout the literature. InHumans, repaglinide is predominantly cleared by hepatic metabolism involving cytochrome P450 (P450) 3A4 and 2C8 and UGT1A1 and 1A3. Gemfibrozil and its glucuronide metabolite inhibit CYP2C8 and UGT1A1, as well as the hepatic uptake transporter OATP1B1.

These factors have been implicated in the clinical interaction. A gemfibrozil / repaglinide DDI resulting in increased repaglinide and metabolite plasma exposure (>3-fold) and a vectoral shift in elimination pathways from biliary to urinary excretion following administration of gemfibrozil was previously established in male Sprague-Dawley rats. In that study, negligible effects on liver enzyme activity were observed following gemfibrozil treatment, suggesting that the DDI in rats was unlikely to be caused by P450 or UGT inhibition. In the present study, the potential role of uptake transporter proteins in the interaction was explored in vitro.

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