Pharmacokinetic Model of Tenofovir and Emtricitabine and Their Intracellular Metabolites in Patients in the ANRS 134-COPHAR 3 Trial Using Dose Records.

HIV antiretroviral mixed-effect models nonlinear models pharmacogenetics pharmacokinetics

Journal

Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061

Informations de publication

Date de publication:
17 05 2023
Historique:
medline: 19 5 2023
pubmed: 26 4 2023
entrez: 26 4 2023
Statut: ppublish

Résumé

Tenofovir (TFV) and emtricitabine (FTC) are part of the recommended highly active antiretroviral therapy (ART). Both molecules show a large interindividual pharmacokinetic (PK) variability. Here, we modeled the concentrations of plasma TFV and FTC and their intracellular metabolites (TFV diphosphate [TFV-DP] and FTC triphosphate [FTC-TP]) collected after 4 and 24 weeks of treatment in 34 patients from the ANRS 134-COPHAR 3 trial. These patients received daily (QD) atazanavir (300 mg), ritonavir (100 mg), and a fixed-dose combination of coformulated TFV disoproxil fumarate (300 mg) and FTC (200 mg). Dosing history was collected using a medication event monitoring system. A three-compartment model with absorption delay (

Identifiants

pubmed: 37098914
doi: 10.1128/aac.02339-18
pmc: PMC10190280
doi:

Substances chimiques

Tenofovir 99YXE507IL
Emtricitabine G70B4ETF4S
Anti-HIV Agents 0
triphosphoric acid NU43IAG5BC

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0233918

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

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Auteurs

Julie Bertrand (J)

UMR 1137, IAME, INSERM, Université Paris Cité, Paris, France.

Aurélie Barrail-Tran (A)

AP-HP, Hôpital Bicêtre, Pharmacie Clinique, Le Kremlin-Bicêtre, France.
UMR 1184, Center for Immunology of Viral Infections and Autoimmune Diseases, INSERM, Université Paris Sud, Paris, France.

Lucie Fayette (L)

UMR 1137, IAME, INSERM, Université Paris Cité, Paris, France.

Rada Savic (R)

Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, USA.

Cécile Goujard (C)

AP-HP, Hôpital Bicêtre, Service de médecine interne et d'immunologie clinique, Le Kremlin-Bicêtre, France.
CESP, Team Epidémiologie Clinique, INSERM UMR 1018, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre, France.

Elina Teicher (E)

AP-HP, Hôpital Bicêtre, Service de médecine interne et d'immunologie clinique, Le Kremlin-Bicêtre, France.

Caroline Barau (C)

AP-HP, Hôpital Henri Mondor, Plateforme de Ressources Biologiques, Créteil, France.

Alain Pruvost (A)

Département Médicaments et Technologies pour la Santé, SPI, CEA, INRAE, Université Paris Saclay, Paris, France.

Anne-Marie Taburet (AM)

AP-HP, Hôpital Bicêtre, Pharmacie Clinique, Le Kremlin-Bicêtre, France.
UMR 1184, Center for Immunology of Viral Infections and Autoimmune Diseases, INSERM, Université Paris Sud, Paris, France.

France Mentré (F)

UMR 1137, IAME, INSERM, Université Paris Cité, Paris, France.

Céline Verstuyft (C)

CESP, Team Epidémiologie Clinique, INSERM UMR 1018, Faculté de Médecine, Univ Paris-Saclay, Le Kremlin Bicêtre, France.
AP-HP, Hôpital Bicêtre, Service de génétique moléculaire et pharmacogénétique, Le Kremlin-Bicêtre, France.

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