HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Sign In to gain access to subscriptions and/or personal tools.

This Article Full Text Full Text (PDF) All Versions of this Article: 0091270008322908v1 48/11/1282    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gagnieu, M.-C. Articles by Tod, M. Search for Related Content PubMed PubMed Citation Articles by Gagnieu, M.-C. Articles by Tod, M. Social Bookmarking                         What's this?

Population Pharmacokinetics of Tenofovir in AIDS Patients

From the Hospices Civils de Lyon, Laboratoire de pharmacologie, Hôpital Edouard Herriot, Lyon, France (Dr Gagnieu); Hospices Civils de Lyon, Laboratoire de ciblage thérapeutique en cancérologie, Centre Hospitalier Lyon-Sud, Pierre Bénite, France (Dr Guitton); Université de Lyon, Laboratoire de Toxicologie, ISPB, faculté de pharmacie, Lyon, France (Dr El Barkil, Dr Guitton, Dr Tod); Hospices Civils de Lyon, Service d'Immunologie Clinique, Hôpital Edouard Herriot, Lyon, France (Dr Livrozet); Hospices Civils de Lyon, Service de Gastroenterologie, Hôpital de l'Hotel-Dieu, Lyon, France (Dr Cotte, Dr Miailhes); and Hospices Civils de Lyon, Service des maladies infectieuses et tropicales, Hôpital de la Croix-Rousse, Lyon, France (Dr Boibieux).

The interindividual variability of tenofovir pharmacokinetics in HIV+ patients is quite large, but the sources of variability are incompletely understood. Intraindividual variability has not been characterized, although it may have an impact on efficacy and therapeutic drug monitoring. The aims of the study were to estimate intraindividual variability of tenofovir clearance and to assess interactions with associated antiviral drugs. Tenofovir concentrations (median 2; range, 1-5) were measured in 175 patients during several dosing intervals. Covariates and dosing regimen of associated antiretroviral drugs were recorded prospectively. The data were analyzed by a population approach. The final model was a 2-compartment model with first-order absorption rate. The elimination clearance was found to be related to the ratio of body weight to serum creatinine. Among the 15 drugs coadministered, no interaction on tenofovir kinetics was significant. The global variability of CL/F, after accounting for variability to variation of body weight and serum creatinine, was about 50%, with 20% due to interindividual variability and 30% due to interoccasion variability. In a few patients, clearance (and AUC) could vary by a factor of 2 between occasions. The interoccasion variability was not related to the delay between occasions. In the context of drug monitoring, for a given patient, the dose should not be adapted unless the variation of concentration between 2 occasions is large, or the 24-hour trough concentration at steady state is lower than 12 µg/L.

Key Words: Tenofovir • pharmacokinetics • drug interaction • intraindividual variability

Address for reprints: Dr Guitton Jérôme, Laboratoire de toxicologie, Université Lyon I, ISPB, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France; e-mail: jerome.guitton{at}recherche.univ-lyon1.fr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?