title: Correlation between UGT1A1 polymorphisms and raltegravir plasma trough concentrations in Japanese HIV-1-infected patients.
abstract: Raltegravir (RAL), an HIV integrase inhibitor, is metabolized mainly by UDP-glucuronosyltransferase 1A1 (UGT1A1). Polymorphisms in UGT1A1 may cause alterations in the pharmacodynamics of RAL, which is taken twice daily with no dietary restrictions. We compared the effect of two polymorphic alleles in this gene, UGT1A1*6 and UGT1A1*28 on plasma RAL concentrations in Japanese HIV-1-infected patients. Of 114 Japanese HIV-1-infected patients who received RAL, the frequencies of UGT1A1*6 and UGT1A1*28 were 18% and 13%, respectively. The percentage of homozygotes for UGT1A1*6 and UGT1A1*28 was 6% and 4%, respectively, the percentage of compound heterozygotes for UGT1A1*6 and UGT1A1*28 was 2%, and that of heterozygotes for UGT1A1*6 and UGT1A1*28 was 22% and 17%, respectively. RAL plasma trough concentrations were compared for each polymorphism. Significantly higher levels of RAL were observed with patients who were homozygous for UGT1A1*6 (median: 1.0 μg/mL) than for the normal allele (median: 0.11 μg/mL; p = 0.021). Multivariate logistic regression analysis showed that the presence of one or two alleles of UGT1A1*6 or two alleles of UGT1A1*28 were independent factors associated with high RAL plasma trough concentrations (≥ 0.17 μg/mL). These results indicated that UGT1A1*6 and UGT1A1*28 are both factors influencing the RAL plasma trough concentrations in Japanese HIV-1-infected patients.
authors.affiliation: Department of Pharmacy, National Hospital Organization Osaka National Hospital, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yagura
authors.affiliation: AIDS Medical Center, National Hospital Organization Osaka National Hospital, Japan. Electronic address: dai@onh.go.jp.
authors.forename: Dai
authors.initials: D
authors.lastname: Watanabe
authors.affiliation: AIDS Medical Center, National Hospital Organization Osaka National Hospital, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Ashida
authors.affiliation: Department of Pharmacy, National Hospital Organization Osaka National Hospital, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kushida
authors.affiliation: AIDS Medical Center, National Hospital Organization Osaka National Hospital, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hirota
authors.affiliation: AIDS Medical Center, National Hospital Organization Osaka National Hospital, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Ikuma
authors.affiliation: AIDS Medical Center, National Hospital Organization Osaka National Hospital, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: AIDS Medical Center, National Hospital Organization Osaka National Hospital, Japan.
authors.forename: Keishiro
authors.initials: K
authors.lastname: Yajima
authors.affiliation: AIDS Medical Center, National Hospital Organization Osaka National Hospital, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kasai
authors.affiliation: AIDS Medical Center, National Hospital Organization Osaka National Hospital, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishida
authors.affiliation: AIDS Medical Center, National Hospital Organization Osaka National Hospital, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Uehira
authors.affiliation: Department of Pharmacy, National Hospital Organization Himeji Medical Center, Japan.
authors.forename: Munehiro
authors.initials: M
authors.lastname: Yoshino
authors.affiliation: AIDS Medical Center, National Hospital Organization Osaka National Hospital, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Shirasaka
mesh_terms: D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D019428:HIV Integrase Inhibitors / Q000378:metabolism / Q000627:therapeutic use; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007564:Japan; D011110:Polymorphism, Genetic; D000068898:Raltegravir Potassium / Q000097:blood* / Q000627:therapeutic use*; D012044:Regression Analysis; D000099148:UGT1A1 Enzyme
chemical_list: D014453:Glucuronosyltransferase; D019428:HIV Integrase Inhibitors; D000068898:Raltegravir Potassium; D000099148:UGT1A1 Enzyme
keywords: HIV-1; Polymorphisms; Raltegravir; UGT1A1