Dolutegravir Population Pharmacokinetics in a Real-Life Cohort of People Living With HIV Infection: A Covariate Analysis

Therapeutic Drug Monitoring
Francois ParantMarie-Claude Gagnieu

Abstract

There are growing concerns about dolutegravir (DTG)-related neuropsychiatric adverse events and about differences in the characteristics of people living with HIV infection (PLWH) potentially associated with higher risks of said side effects. Several studies have shown that DTG was stopped more frequently among women, older PLWH, and PLWH who initiated abacavir (ABC) at the same time. This study aimed to clarify the factors affecting the pharmacokinetics (PKs) of DTG in a real-life cohort of PLWH using a population PK approach. The model-building strategy was based on a previously published model developed from premarketing trials (1-compartment model with first-order absorption and a lag time). Sparse therapeutic drug monitoring data were obtained from a real-life cohort of 279 PLWH, and population PK analysis was performed using Monolix software. A stepwise covariate model-building strategy was used to evaluate any relevant effects of age, body weight, gender, total bilirubin, smoking status, formulations of DTG, morning versus evening dosing, backbone therapy, and other comedications including CYP/UGT inducers/inhibitors. For a typical 70-kg PLWH, the apparent clearance (CL/F) and apparent volume of distribution (V/F) were 0...Continue Reading

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Citations

May 24, 2019·The Journal of Antimicrobial Chemotherapy·Catalina BarceloUNKNOWN Swiss HIV Cohort Study
Aug 28, 2020·Expert Opinion on Drug Metabolism & Toxicology·Nuti DesaiTheodore J Cory
Apr 30, 2021·Expert Opinion on Drug Metabolism & Toxicology·Andrea CalcagnoStefano Bonora
Sep 16, 2021·AIDS Patient Care and STDs·Lucia TaramassoUNKNOWN Behalf of the CISAI Study Group

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