Abstract
Dolutegravir (DTG) is a potent integrase inhibitor of human immunodeficiency virus. Because DTG is a substrate of the efflux transporter ABCG2 and ABCG2 is highly polymorphic, we asked whether dose adjustment of DTG is needed for ABCG2-deficient individuals. Using Abcg2-null mice, the current work investigated the impact of ABCG2 deficiency on DTG metabolism and pharmacokinetics. Compared with wild-type mice, no statistically significant difference was found in the systemic and tissue-specific (liver, kidney, and brain) pharmacokinetics of DTG in Abcg2-null mice. In addition, ABCG2 deficiency had no statistically significant impact on the production and excretion of DTG metabolites. In summary, this study demonstrated that deficiency of ABCG2 does not alter DTG metabolism and pharmacokinetics, suggesting that dose adjustment of DTG is not needed for individuals with ABCG2 deficiency. SIGNIFICANCE STATEMENT: The current work demonstrated that deficiency of ATP-binding cassette subfamily G member 2 (ABCG2) does not alter Dolutegravir (DTG) metabolism and pharmacokinetics, suggesting that dose adjustment of DTG is not needed for individuals with ABCG2 deficiency.