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Physiologically‐Based Pharmacokinetic Modeling Combined with Swiss HIV Cohort Study Data Supports No Dose Adjustment of Bictegravir in Elderly Individuals Living With HIV
Author(s) -
Stader Felix,
Courlet Perrine,
Decosterd Laurent A.,
Battegay Manuel,
Marzolini Catia
Publication year - 2021
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.2178
Subject(s) - medicine , physiologically based pharmacokinetic modelling , pharmacokinetics , cohort , dosing , cohort study
Clinical studies in aging people living with HIV (PLWH) are sparse for the novel integrase inhibitor bictegravir, leading to some uncertainty about dosing recommendations for elderly PLWH. The objective of this study was to investigate the continuous impact of aging on bictegravir pharmacokinetics by combining clinically observed data with modeling to support a safe and efficient anti‐HIV therapy with advanced age. A physiologically‐based pharmacokinetic (PBPK) model was developed for bictegravir with clinically observed data from phase I studies. The predictive model performance was verified using bictegravir plasma concentrations sampled as part of the general therapeutic drug monitoring (TDM) program of the Swiss HIV Cohort Study in young (20–55 years) and elderly PLWH (55–85 years). The verified PBPK model subsequently predicted the continuous impact of aging on bictegravir pharmacokinetics across adulthood (20–99 years). Bictegravir exposure was unchanged in elderly compared with young PLWH when analyzing the TDM data of the Swiss HIV Cohort Study. PBPK simulations predicted clinically observed data from 60 young and 32 elderly PLWH mostly within the 95% confidence interval, demonstrating the predictive power of the used modeling approach. Simulations predicted drug exposure to increase up to 40% during adulthood, which was not statistically significantly different from the age‐related pharmacokinetic changes of other HIV and non‐HIV drugs. Sex had no impact on the age‐related changes of bictegravir pharmacokinetics. Considering the safety margin of bictegravir, a dose adjustment for the novel integrase inhibitor is a priori not necessary in elderly PLWH in the absence of severe comorbidities.