Pharmacokinetics of Raltegravir in Individuals With UGT1A1 Polymorphisms

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Abstract
Raltegravir is a human immunodeficiency virus–1 (HIV‐1) integrase strand transfer inhibitor metabolized by glucuronidation via UDP‐glucuronosyltransferase 1A1 (UGT1A1). In this study, 30 subjects with a UGT1A1*28/*28 genotype (associated with decreased activity of UGT1A1) and 27 UGT1A1*1/*1 control subjects (matched by race, age, gender, and body mass index) received a single 400‐mg dose of raltegravir after fasting. No serious adverse experiences were reported, and there were no discontinuations due to adverse experiences. The geometric mean ratio (GMR) (UGT1A1*28/*28 to UGT1A1*1/*1) and 90% confidence interval (CI) were 1.41 (0.96, 2.09) for raltegravir area under the concentration–time curve (AUC0–∞), 1.40 (0.86, 2.28) for maximum plasma concentration (Cmax), and 1.91 (1.43, 2.55) for concentration at the 12‐h time point (C12 h). No clinically important differences in time to maximum concentration (Tmax) or half‐life were observed. Plasma concentrations of raltegravir are modestly higher in individuals with the UGT1A1*28/*28 genotype than in those with the UGT1A1*1/*1 genotype. This increase is not clinically significant, and therefore no dose adjustment of raltegravir is required for individuals with the UGT1A1*28/*28 genotype. Clinical Pharmacology & Therapeutics (2009); 85, 6, 623–627 doi:10.1038/clpt.2009.12

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