Short communication: lack of correlation between UGT1A1*6, *28 genotypes, and plasma raltegravir concentrations in Japanese HIV type 1-infected patients

AIDS Res Hum Retroviruses. 2012 Aug;28(8):776-9. doi: 10.1089/AID.2011.0231. Epub 2011 Nov 9.

Abstract

Raltegravir is metabolized by glucuronidation via UDP-glucuronosyltransferase 1A1 (UGT1A1). We analyzed the genotypes of UGT1A1 (*6, *27, and *28) and their contribution to plasma raltegravir concentrations in 56 Japanese HIV-1-infected patients in the National Hospital Organization Nagoya Medical Center of Japan. Among the 56 patients, the UGT1A1 genotype in two patients was *6 homozygote. Heterozygous variants were found in 13 patients for *6 and in 11 patients for *28, while all of the patients were found to carry wild-type sequences at the position corresponding to the *27 allele. Plasma raltegravir concentration of a male patient with *6 homozygote (0.53 μg/ml) was modestly higher than that of patients with wild type (0.12 μg/ml) or *6 heterozygote (0.16 μg/ml). Another female patient with the *6 homozygote had a low plasma raltegravir concentration (0.03 μg/ml). Patients heterozygous for the *6 or *28 allele did not display significantly different plasma raltegravir concentrations compared to patients homozygous for the respective wild-type allele. Thus, in the present study, we showed that heterozygous reduced-function *6 and *28 alleles appear to have no significant effect on plasma raltegravir concentrations in Japanese HIV-1-infected patients. However, variability in raltegravir concentration and small patient population precluded a correlation between UGT1A1*6 homozygosity and plasma raltegravir concentration. To clarify the contribution of UGT1A1*6 or *28 polymorphisms to plasma raltegravir concentrations, further investigations on larger subject populations are required.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Retroviral Agents / blood*
  • Anti-Retroviral Agents / therapeutic use
  • Asian People
  • Female
  • Genotype
  • Glucuronosyltransferase / genetics*
  • HIV Infections / drug therapy
  • HIV Infections / ethnology
  • HIV Infections / genetics*
  • HIV-1*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Pyrrolidinones / blood*
  • Pyrrolidinones / therapeutic use
  • Raltegravir Potassium
  • Young Adult

Substances

  • Anti-Retroviral Agents
  • Pyrrolidinones
  • Raltegravir Potassium
  • UGT1A1 enzyme
  • Glucuronosyltransferase