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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals
Antimicrobial Agents and Chemotherapy, Volume 56, No. 6, Year 2012
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Description
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 onceand 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. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Fayet-Mello, Aurélie
Switzerland, Lausanne
Université de Lausanne Unil
Neely, Michael Noel
United States, Los Angeles
University of Southern California
Owen, Andrew
United Kingdom, Liverpool
University of Liverpool
Boffito, Marta A.
United Kingdom, London
Chelsea and Westminster Foundation Trust
Cavassini, Matthias L.
Switzerland, Lausanne
Université de Lausanne Unil
Günthard, Hüldrych Fritz
Switzerland, Zurich
Universität Zürich
Buclin, Thierry J.
Switzerland, Lausanne
Université de Lausanne Unil
Aouri, Manel
Switzerland, Lausanne
Université de Lausanne Unil
Telenti, Amalio
Switzerland, Lausanne
Université de Lausanne Unil
Décosterd, Laurent Arthur
Switzerland, Lausanne
Université de Lausanne Unil
Csajka, Chantal
Switzerland, Lausanne
Université de Lausanne Unil
Battegay, Manuel
Unknown Affiliation
Bernasconi, Enos
Unknown Affiliation
Böni, Jürg
Unknown Affiliation
Bucher, Heíner C.C.
Unknown Affiliation
Bürgisser, Ph
Unknown Affiliation
Calmy, Alexandra L.
Unknown Affiliation
Cattacin, Sandro
Unknown Affiliation
Cavassini, Matthias
Unknown Affiliation
Dubs, Rolf W.
Unknown Affiliation
Egger, Matthias
Unknown Affiliation
Elzi, Luigia
Unknown Affiliation
Fischer, Marek
Unknown Affiliation
Flepp, Markus J.
Unknown Affiliation
Fontana, Adriano
Unknown Affiliation
Francioli, Patrick B.
Unknown Affiliation
Furrer, Hansjakob
Unknown Affiliation
Fux, Christoph Andreas
Unknown Affiliation
Gorgievski, Meri
Unknown Affiliation
Hirsch, Hans H.
Unknown Affiliation
Hirschel, B. J.
Unknown Affiliation
Hösli, Irene Mathilde
Unknown Affiliation
Kahlert, Christian R.
Unknown Affiliation
Kaiser, Laurent K.
Unknown Affiliation
Karrer, Urs
Unknown Affiliation
Kind, Christian H.
Unknown Affiliation
Klimkait, Thomas
Unknown Affiliation
Ledergerber, Bruno
Unknown Affiliation
Martinetti, Gladys
Unknown Affiliation
Müller, Nicolas J.
Unknown Affiliation
Nadal, David
Unknown Affiliation
Paccaud, Fred Michel
Unknown Affiliation
Pantaleo, Giuseppe P.
Unknown Affiliation
Rauch, Andri
Unknown Affiliation
Regenass, Stephan
Unknown Affiliation
Rickenbach, Martin
Unknown Affiliation
Rudin, Christoph
Unknown Affiliation
Schmid, Patrick
Unknown Affiliation
Schültze, Detlev
Unknown Affiliation
Schüpbach, Jörg Rg
Unknown Affiliation
Speck, Roberto F.
Unknown Affiliation
Martínez de Tejada, Begoῆa
Unknown Affiliation
Taffé, Patrick
Unknown Affiliation
Trkola, Alexandra
Unknown Affiliation
Vernazza, Pietro Luigi
Unknown Affiliation
Weber, Rainer
Unknown Affiliation
Yerly, Sabine T.B.D.
Unknown Affiliation
Statistics
Citations: 37
Authors: 57
Affiliations: 6
Identifiers
Doi:
10.1128/AAC.05424-11
ISSN:
10986596
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study