Development of a Semi-Mechanistic Population Pharmacokinetic Model for Predicting Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide Exposure in Plasma and Cellular Matrices During Pregnancy and Postpartum
Rattachement africain : us, Afrique du Sud. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
BACKGROUND AND OBJECTIVE: Tenofovir (TFV)-based regimens are backbones of both HIV treatment and pre-exposure prophylaxis during pregnancy. Multiple studies have shown up to one-third decreases in dried blood spot tenofovir-diphosphate concentrations during pregnancy among participants taking tenofovir disoproxil fumarate (TDF). Currently, there are no mechanism-based models describing the pharmacokinetics of tenofovir diphosphate (the active anabolite) in peripheral blood mononuclear cells (PBMCs) of pregnant individuals receiving TDF or tenofovir alafenamide (TAF), and the mechanisms behind observed differences between dried blood spots and PBMCs remain unclear. METHODS: To address this gap, we developed a semi-mechanistic model to simultaneously describe the pharmacokinetics of all clinically relevant TDF and TAF-derived moieties and conducted clinical trial simulations to compare TDF and TAF pharmacokinetics during pregnancy and postpartum. RESULTS: The pharmacokinetics of plasma TAF and TFV were best described by one-compartment and two-compartment models, respectively, with first-order absorption. A transit compartment was included to reflect the slower elimination rate of plasma TFV after receiving TAF. Cellular matrix PBMC and dried blood spots were included using a biophase model. For TDF, plasma TFV apparent clearance increased by 24.9% and 13.1% during the second and third trimesters of pregnancy, respectively, compared with non-pregnant populations. In the postpartum period, plasma TFV apparent clearance in pregnant women was 9.3% lower than in non-pregnant women. The bioavailability for TAF decreased by 17.3% and 5.1% during the second and third trimesters, respectively, and increased by 18% during the postpartum period relative to non-pregnant women. In pregnant women, simulations showed that TAF maintains approximately five times higher tenofovir diphosphate concentrations in PBMCs compared with TDF during the second and third trimesters, despite a decrease in PBMC tenofovir diphosphate concentrations for both drugs. This finding is consistent with the higher PBMC loading effect of TAF observed in non-pregnant populations. CONCLUSIONS: Our semi-mechanistic model provides a framework for understanding pregnancy-associated pharmacokinetic changes and supports future research to refine dosing strategies for HIV treatment and prevention in pregnancy.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Development of a Semi-Mechanistic Population Pharmacokinetic Model for Predicting Tenofovir Disoproxil Fumarate and Tenofovir Alafenamide Exposure in Plasma and Cellular Matrices During Pregnancy and Postpartum
- Date Crossref
- 12/11/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University at Buffalo pays non établi dans la noticeUniversité ou école supérieure
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University of Colorado Anschutz pays non établi dans la noticeUniversité ou école supérieure
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University of Montana pays non établi dans la noticeUniversité ou école supérieure
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Eastern Virginia Medical School pays non établi dans la noticeUniversité ou école supérieure
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Old Dominion University CONRAD pays non établi dans la noticeUniversité ou école supérieure
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University of California San Diego Pediatrics Department pays non établi dans la noticeUniversité ou école supérieure
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University at Buffalo, University of Colorado Anschutz et University of Montana, avec 9 autres affiliations. Pays d’affiliation : Afrique du Sud.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.