Stader, Felix, Courlet, Perrine, Decosterd, Laurent A 
ORCID: 0000-0002-9840-1325, Battegay, Manuel and Marzolini, Catia ORCID: 0000-0002-2312-7050
(2021)
Physiologically-Based Pharmacokinetic Modeling Combined with Swiss HIV Cohort Study Data Supports No Dose Adjustment of Bictegravir in Elderly Individuals Living With HIV.
Clinical pharmacology and therapeutics, 109 (4).
pp. 1025-1029.
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Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, HIV Infections, Amides, Piperazines, Pyridones, Heterocyclic Compounds, 3-Ring, HIV Integrase Inhibitors, Anti-Retroviral Agents, Drug Monitoring, Metabolic Clearance Rate, Area Under Curve, Aging, Models, Biological, Adult, Aged, Aged, 80 and over, Middle Aged, Switzerland, Female, Male, Young Adult |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 29 Feb 2024 08:17 |
| Last Modified: | 29 Feb 2024 08:17 |
| DOI: | 10.1002/cpt.2178 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178974 |
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