Related Experiment Video
Updated: May 4, 2026

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
Evaluation of the effect of UGT1A1 polymorphisms on dolutegravir pharmacokinetics
Shuguang Chen1, Pamela St Jean, Julie Borland
1GlaxoSmithKline, Research Triangle Park, NC, USA.
Aim:
To evaluate potential pharmacogenetic effects of UGT1A1 polymorphisms on the pharmacokinetics (PK) of dolutegravir (Tivicay®; ViiV Healthcare, NC, USA), an HIV-1 integrase inhibitor.
Patients & Methods:
Analysis of pooled data from nine Phase I and II clinical studies was undertaken for 89 subjects receiving repeat dolutegravir 50 mg once daily (tablet formulation) who were genotyped for known UGT1A1 functional variants.
Results:
Geometric mean ratio (92% CI) for subjects carrying low (*28/*28 and *28/*37) and reduced activity (*1/*6, *1/*28, *1/*37, *28/*36 and *36/*37) polymorphisms compared with subjects with normal activity (*1/*1 and *1/*36) showed decreased oral clearance (CL/F; 0.765 [92% CI: 0.659-0.889]), increased area under the concentration-time curve (AUC(0-τ); 1.307 [1.125-1.518]) and C(max) (1.221 [1.063-1.402]), respectively.
Conclusion:
Increased dolutegravir exposure in carriers of UGT1A1 reduced function polymorphisms is not clinically significant based on accumulated safety data so dose adjustment in these individuals is not required.
Related Concept Videos
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

