Physiologically-Based Pharmacokinetic Modeling Combined with Swiss HIV Cohort Study Data Supports No Dose Adjustment of Bictegravir in Elderly Individuals Living With HIV.

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State: Public
Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_04518947F853
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Physiologically-Based Pharmacokinetic Modeling Combined with Swiss HIV Cohort Study Data Supports No Dose Adjustment of Bictegravir in Elderly Individuals Living With HIV.
Journal
Clinical pharmacology and therapeutics
Author(s)
Stader F., Courlet P., Decosterd L.A., Battegay M., Marzolini C.
ISSN
1532-6535 (Electronic)
ISSN-L
0009-9236
Publication state
Published
Issued date
04/2021
Peer-reviewed
Oui
Volume
109
Number
4
Pages
1025-1029
Language
english
Notes
Publication types: Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
Adult, Aged, Aged, 80 and over, Aging/physiology, Amides/pharmacokinetics, Amides/therapeutic use, Anti-Retroviral Agents/pharmacokinetics, Anti-Retroviral Agents/therapeutic use, Area Under Curve, Drug Monitoring, Female, HIV Infections/drug therapy, HIV Integrase Inhibitors/pharmacokinetics, HIV Integrase Inhibitors/therapeutic use, Heterocyclic Compounds, 3-Ring/pharmacokinetics, Heterocyclic Compounds, 3-Ring/therapeutic use, Humans, Male, Metabolic Clearance Rate, Middle Aged, Models, Biological, Piperazines/pharmacokinetics, Piperazines/therapeutic use, Pyridones/pharmacokinetics, Pyridones/therapeutic use, Switzerland, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
08/02/2021 14:46
Last modification date
27/08/2023 7:08
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