Pharmaceutics
Impact of Body Weight and Combined UGT1A1 and NR1I2 Polymorphisms on Dolutegravir Pharmacokinetics Among Thai People Living with HIV: A Population Pharmacokinetic Analysis
By Anan Chanruang, Angela K. Birnbaum, Sílvia M. Illamola and 8 others.
Abstract
Background/Objectives: Despite its role as a first-line therapy for Thai people living with HIV (PLWH), dolutegravir (DTG) exhibits significant pharmacokinetic (PK) variability influenced by both genetic and non-genetic factors. This variability may contribute to an increased incidence of neuropsychiatric adverse events (NP-AEs) at the standard 50 mg once daily (OD) dose.
Methods
To evaluate the impact of relevant covariates, a population PK model of DTG was developed using 1122 DTG plasma concentrations from 221 Thai PLWH. Monte Carlo simulations were performed to evaluate the probability of target attainment for pre-defined efficacy and safety thresholds across different dosage regimens.