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A multicompartment population PK model to predict tenofovir and emtricitabine mucosal tissue concentrations for HIV prevention
- Source :
- CPT: Pharmacometrics & Systems Pharmacology, Vol 12, Iss 12, Pp 1922-1930 (2023)
- Publication Year :
- 2023
- Publisher :
- Wiley, 2023.
-
Abstract
- Abstract A priori use of mathematical modeling and simulation to predict outcomes from incomplete adherence or reduced frequency dosing strategies may mitigate the risk of clinical trial failure with HIV pre‐exposure prophylaxis regimens. We developed a semi‐physiologic population pharmacokinetic model for two antiretrovirals and their active intracellular metabolites in three mucosal tissues using pharmacokinetic data from a phase I, dose‐ranging study. Healthy female volunteers were given a single oral dose of tenofovir disoproxil fumarate (150, 300, or 600 mg) or emtricitabine (100, 200, or 400 mg). Simultaneous co‐modeling of all data was performed on a Linux cluster. A 16 compartment, bolus input, linear kinetic model best described the data, containing 986 observations in 23 individuals across three matrices and four analytes. Combined with a defined efficacious concentration target in mucosal tissues, this model can be used to optimize the dose and dosing frequency through Monte‐Carlo simulations.
- Subjects :
- Therapeutics. Pharmacology
RM1-950
Subjects
Details
- Language :
- English
- ISSN :
- 21638306
- Volume :
- 12
- Issue :
- 12
- Database :
- Directory of Open Access Journals
- Journal :
- CPT: Pharmacometrics & Systems Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.84690a7c263a4274a59a10aac8b74601
- Document Type :
- article
- Full Text :
- https://doi.org/10.1002/psp4.13042