title: Short communication: lack of correlation between UGT1A1*6, *28 genotypes, and plasma raltegravir concentrations in Japanese HIV type 1-infected patients.
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.
authors: Department of Pharmacy, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.
authors: Atsushi
authors: A
authors: Hirano
authors: Kenji
authors: K
authors: Ikemura
authors: Masaaki
authors: M
authors: Takahashi
authors: Masaaki
authors: M
authors: Shibata
authors: Katsuo
authors: K
authors: Amioka
authors: Toshiharu
authors: T
authors: Nomura
authors: Yoshiyuki
authors: Y
authors: Yokomaku
authors: Wataru
authors: W
authors: Sugiura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044966:Anti-Retroviral Agents / Q000097:blood* / Q000627:therapeutic use; D044466:Asian People; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011760:Pyrrolidinones / Q000097:blood* / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D055815:Young Adult; D000099148:UGT1A1 Enzyme
chemical_list: D044966:Anti-Retroviral Agents; D014453:Glucuronosyltransferase; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D000099148:UGT1A1 Enzyme