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Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Arab-Alameddine Mona, Fayet-Mello Aurélie, Lubomirov Rubin, Neely Michael, di Iulio Julia, Owen Andrew, Boffito Marta, Cavassini Matthias, Günthard Huldrych F, Rentsch Katharina, Buclin Thierry, Aouri Manel, Telenti Amalio, Decosterd Laurent Arthur, Rotger Margalida, Csajka Chantal, Swiss HIV Cohort Study Group,
Project Pharmacocinétique de population, pharmacogénétique, et profils métaboliques de la thérapie anti-HIV
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Original article (peer-reviewed)

Journal Antimicrobial agents and chemotherapy
Volume (Issue) 56(6)
Page(s) 2959 - 66
Title of proceedings Antimicrobial agents and chemotherapy
DOI 10.1128/AAC.05424-11


The objectives of this study were to characterize raltegravir (RAL) population pharmacokinetics in HIV-positive (HIV(+)) and healthy individuals, identify influential factors, and search for new candidate genes involved in UDP glucuronosyltransferase (UGT)-mediated glucuronidation. The pharmacokinetic analysis was performed with NONMEM. Genetic association analysis was performed with PLINK using the relative bioavailability as the phenotype. Simulations were performed to compare once- and twice-daily regimens. A 2-compartment model with first-order absorption adequately described the data. Atazanavir, gender, and bilirubin levels influenced RAL relative bioavailability, which was 30% lower in HIV(+) than in healthy individuals. UGT1A9*3 was the only genetic variant possibly influencing RAL pharmacokinetics. The majority of RAL pharmacokinetic variability remains unexplained by genetic and nongenetic factors. Owing to the very large variability, trough drug levels might be very low under the standard dosing regimen, raising the question of a potential relevance of therapeutic drug monitoring of RAL in some situations.