Authors: Xavière Panhard Mayeule Legrand AnneMarie Taburet Bertrand Diquet Cécile Goujard France Mentré the Cophar 1 ANRS 102 Study Group
Publish Date: 2007/08/11
Volume: 63, Issue: 11, Pages: 1019-1029
Abstract
Population PK of LMV STV and ZDV was separately evaluated from plasma concentrations obtained in 54 39 and 27 HIV1infected patients respectively enrolled in the COPHAR1ANRS102 trial The primary objective of this trial was to study the pharmacokinetics of indinavir IDV and nelfinavir NFV in treated patients with a sustained virological response Concentrations of nucleoside analogs NA were measured in plasma as a secondary objective A onecompartment model with firstorder elimination was used with zeroorder absorption for LMV and firstorder absorption for STV and ZDVMean parameters interpatient variability in coefficient of variation CV of LMV STV and ZDV were oral volume of distribution V/F 145 l 52 24 l 81 and 248 l 80 oral clearance Cl/F 32 l/h 16 l/h 74 and 124 l/h 51 respectively For LMV absorption duration T a was 146 h 64 For STV and ZDV k a was 046 h−1 and 29 h−1 respectively We found a systematic effect of combination with NFV vs IDV We found that intrapatient variability was greater than interpatient variability except for STV and greater than 55 for the three drugsThis trial enabled the estimation of the population PK parameters of three NA in patients with a sustained virological response and the median curves could be used as references for concentrationcontrolled strategies We observed as for the protease inhibitors a great variability of PK parametersWe gratefully acknowledge all members of the scientific committee of the COPHAR1ANRS102 trial Prof V Calvez Hôpital PitiéSalpétrière Paris Prof G Chêne INSERM U330 Bordeaux Prof B Diquet Hôpital PitiéSalpétrière Paris Prof C Katlama Hôpital PitiéSalpétrière Paris Prof C Leport Hôpital Bichat Paris Mrs A Metro ANRS Paris Dr G Peytavin Hôpital Bichat Paris Prof F Raffi Hôpital Hôtel Dieu Nantes Dr A Roux Hôpital Ambroise Paré Boulogne and Prof D SalmonCeron Hôpital Cochin Paris We would like to thank the investigators in the clinical centres for including patients JM Estavoyer R Laurent Besançon X Bazin Caen C Perrone Garches JF Delfraissy Kremlin Bicêtre F Raffi Nantes E Bouvet F Bricaire S Herson W Rozenbaum D Séréni D Sicard A Simon JL Vildé Paris X Lang Strasbourg and the pharmacological laboratories for performing drug assays B Royer P Muret Besançon M Tod Bobigny AM Taburet Kremlin Bicêtre C Solas Marseille D Hillaire Montpellier E Dailly Nantes B Diquet G Peytavin JM Poirier E Rey H Sauvageon Paris JC Alvarez Versailles We also thank the patients for their participation
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