Related Experiment Video
Updated: Dec 23, 2025

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
ABCG2 Deficiency Does Not Alter Dolutegravir Metabolism and Pharmacokinetics
Junjie Zhu1, Xin Tian1, Amina I Shehu1
1Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy (J.Z., X.T., A.I.S., X.M.) and Division of Infectious Disease, Department of Medicine (D.K.M.), University of Pittsburgh, Pittsburgh, Pennsylvania.
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.
More Related Videos
Related Concept Videos
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
Pharmacokinetics in Pediatric Patients: Drug Excretion
Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Metabolism
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
Factors Influencing Drug Absorption: Disease States and Pharmacology
Substances such as alcohol and specific drugs, including antineoplastics, can also negatively impact drug absorption. For instance,...
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug

