A multicompartment population PK model to predict tenofovir and emtricitabine mucosal tissue concentrations for HIV prevention
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 mo...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-12-01
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| Series: | CPT: Pharmacometrics & Systems Pharmacology |
| Online Access: | https://doi.org/10.1002/psp4.13042 |
| _version_ | 1797388944315252736 |
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| author | Erick Leung Mackenzie L. Cottrell Craig Sykes Nicole White Angela D. M. Kashuba Julie B. Dumond |
| author_facet | Erick Leung Mackenzie L. Cottrell Craig Sykes Nicole White Angela D. M. Kashuba Julie B. Dumond |
| author_sort | Erick Leung |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T22:48:17Z |
| format | Article |
| id | doaj.art-84690a7c263a4274a59a10aac8b74601 |
| institution | Directory Open Access Journal |
| issn | 2163-8306 |
| language | English |
| last_indexed | 2024-03-08T22:48:17Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | CPT: Pharmacometrics & Systems Pharmacology |
| spelling | doaj.art-84690a7c263a4274a59a10aac8b746012023-12-16T18:59:25ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062023-12-0112121922193010.1002/psp4.13042A multicompartment population PK model to predict tenofovir and emtricitabine mucosal tissue concentrations for HIV preventionErick Leung0Mackenzie L. Cottrell1Craig Sykes2Nicole White3Angela D. M. Kashuba4Julie B. Dumond5Division of Pharmacotherapy and Experimental Therapeutics University of North Carolina UNC Eshelman School of Pharmacy Chapel Hill North Carolina USADivision of Pharmacotherapy and Experimental Therapeutics University of North Carolina UNC Eshelman School of Pharmacy Chapel Hill North Carolina USADivision of Pharmacotherapy and Experimental Therapeutics University of North Carolina UNC Eshelman School of Pharmacy Chapel Hill North Carolina USAUniversity of North Carolina School of Medicine Chapel Hill North Carolina USADivision of Pharmacotherapy and Experimental Therapeutics University of North Carolina UNC Eshelman School of Pharmacy Chapel Hill North Carolina USADivision of Pharmacotherapy and Experimental Therapeutics University of North Carolina UNC Eshelman School of Pharmacy Chapel Hill North Carolina USAAbstract 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.https://doi.org/10.1002/psp4.13042 |
| spellingShingle | Erick Leung Mackenzie L. Cottrell Craig Sykes Nicole White Angela D. M. Kashuba Julie B. Dumond A multicompartment population PK model to predict tenofovir and emtricitabine mucosal tissue concentrations for HIV prevention CPT: Pharmacometrics & Systems Pharmacology |
| title | A multicompartment population PK model to predict tenofovir and emtricitabine mucosal tissue concentrations for HIV prevention |
| title_full | A multicompartment population PK model to predict tenofovir and emtricitabine mucosal tissue concentrations for HIV prevention |
| title_fullStr | A multicompartment population PK model to predict tenofovir and emtricitabine mucosal tissue concentrations for HIV prevention |
| title_full_unstemmed | A multicompartment population PK model to predict tenofovir and emtricitabine mucosal tissue concentrations for HIV prevention |
| title_short | A multicompartment population PK model to predict tenofovir and emtricitabine mucosal tissue concentrations for HIV prevention |
| title_sort | multicompartment population pk model to predict tenofovir and emtricitabine mucosal tissue concentrations for hiv prevention |
| url | https://doi.org/10.1002/psp4.13042 |
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