In Vitro Investigations into the Roles of Drug Transporters and Metabolizing Enzymes in the Disposition and Drug Interactions of Dolutegravir, a HIV Integrase Inhibitor

  title={In Vitro Investigations into the Roles of Drug Transporters and Metabolizing Enzymes in the Disposition and Drug Interactions of Dolutegravir, a HIV Integrase Inhibitor},
  author={Melinda J. Reese and Paul M. Savina and Grant T. Generaux and Helen Tracey and Joan E. Humphreys and Eri Kanaoka and Lindsey O. Webster and Kelly A. Harmon and James D. Clarke and Joseph W. Polli},
  journal={Drug Metabolism and Disposition},
  pages={353 - 361}
Dolutegravir (DTG; S/GSK1349572) is a potent HIV-1 integrase inhibitor with a distinct resistance profile and a once-daily dose regimen that does not require pharmacokinetic boosting. This work investigated the in vitro drug transport and metabolism of DTG and assessed the potential for clinical drug-drug interactions. DTG is a substrate for the efflux transporters P-glycoprotein (Pgp) and human breast cancer resistance protein (BCRP). Its high intrinsic membrane permeability limits the impact… 

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