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

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2023 Apr 26

PMID 37098914

Authors

Julie Bertrand

Aurelie Barrail-Tran

Lucie Fayette

Rada Savic

Cecile Goujard

Elina Teicher

Caroline Barau

Alain Pruvost

Anne-Marie Taburet

France Mentre

Celine Verstuyft

Affiliations

Soon will be listed here.

Abstract

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 () was selected to describe the PK of, respectively, TFV/TFV-DP and FTC/FTC-TP. TFV and FTC apparent clearances, 114 L/h (relative standard error [RSE] = 8%) and 18.1 L/h (RSE = 5%), respectively, were found to decrease with age. However, no significant association was found with the polymorphisms rs717620, rs1751034, and rs1045642. The model allows prediction of TFV-DP and FTC-TP concentrations at steady state with alternative regimens.

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