Pharmacokinetics of raltegravir in individuals with UGT1A1 polymorphisms

Clin Pharmacol Ther. 2009 Jun;85(6):623-7. doi: 10.1038/clpt.2009.12. Epub 2009 Mar 11.

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 (AUC(0-infinity)), 1.40 (0.86, 2.28) for maximum plasma concentration (C(max)), and 1.91 (1.43, 2.55) for concentration at the 12-h time point (C(12 h)). No clinically important differences in time to maximum concentration (T(max)) 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Area Under Curve
  • Female
  • Genotype
  • Glucuronosyltransferase / genetics*
  • Glucuronosyltransferase / metabolism
  • HIV Integrase Inhibitors / pharmacokinetics*
  • Half-Life
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Pyrrolidinones / pharmacokinetics*
  • Raltegravir Potassium

Substances

  • HIV Integrase Inhibitors
  • Pyrrolidinones
  • Raltegravir Potassium
  • UGT1A1 enzyme
  • Glucuronosyltransferase