Multiscale model of hepatitis C virus dynamics in plasma and liver following combination therapy

Abstract This work explores the application of a physiologically structured population (PSP) framework in modeling hepatitis C virus (HCV) kinetics. To do so, a model was developed for the viral RNA load in plasma and liver as observed in 15 patients treated with a combination therapy of pegylated i...

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Autores principales:	Xavier Woot de Trixhe, Wojciech Krzyzanski, An Vermeulen, Juan José Perez‐Ruixo
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/408653afc87f4315b2133467334bc8eb
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spelling	oai:doaj.org-article:408653afc87f4315b2133467334bc8eb2021-11-19T15:35:29ZMultiscale model of hepatitis C virus dynamics in plasma and liver following combination therapy2163-830610.1002/psp4.12604https://doaj.org/article/408653afc87f4315b2133467334bc8eb2021-08-01T00:00:00Zhttps://doi.org/10.1002/psp4.12604https://doaj.org/toc/2163-8306Abstract This work explores the application of a physiologically structured population (PSP) framework in modeling hepatitis C virus (HCV) kinetics. To do so, a model was developed for the viral RNA load in plasma and liver as observed in 15 patients treated with a combination therapy of pegylated interferon, ribavirin, and telaprevir. By including both intracellular and extracellular processes of the HCV lifecycle, the model provided a description of the treatment effect on the intracellular HCV lifecycle. Combining PSP models with a nonlinear mixed effects approach in a single model permits a natural inclusion of the direct‐acting antiviral effect on intracellular processes, which can then be integrated with the viral kinetics within the host while accounting for the interindividual variability between patients. This should allow an exploration of the treatment effect within the entire chronic HCV‐infected population.Xavier Woot de TrixheWojciech KrzyzanskiAn VermeulenJuan José Perez‐RuixoWileyarticleTherapeutics. PharmacologyRM1-950ENCPT: Pharmacometrics & Systems Pharmacology, Vol 10, Iss 8, Pp 826-838 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950
spellingShingle	Therapeutics. Pharmacology RM1-950 Xavier Woot de Trixhe Wojciech Krzyzanski An Vermeulen Juan José Perez‐Ruixo Multiscale model of hepatitis C virus dynamics in plasma and liver following combination therapy
description	Abstract This work explores the application of a physiologically structured population (PSP) framework in modeling hepatitis C virus (HCV) kinetics. To do so, a model was developed for the viral RNA load in plasma and liver as observed in 15 patients treated with a combination therapy of pegylated interferon, ribavirin, and telaprevir. By including both intracellular and extracellular processes of the HCV lifecycle, the model provided a description of the treatment effect on the intracellular HCV lifecycle. Combining PSP models with a nonlinear mixed effects approach in a single model permits a natural inclusion of the direct‐acting antiviral effect on intracellular processes, which can then be integrated with the viral kinetics within the host while accounting for the interindividual variability between patients. This should allow an exploration of the treatment effect within the entire chronic HCV‐infected population.
format	article
author	Xavier Woot de Trixhe Wojciech Krzyzanski An Vermeulen Juan José Perez‐Ruixo
author_facet	Xavier Woot de Trixhe Wojciech Krzyzanski An Vermeulen Juan José Perez‐Ruixo
author_sort	Xavier Woot de Trixhe
title	Multiscale model of hepatitis C virus dynamics in plasma and liver following combination therapy
title_short	Multiscale model of hepatitis C virus dynamics in plasma and liver following combination therapy
title_full	Multiscale model of hepatitis C virus dynamics in plasma and liver following combination therapy
title_fullStr	Multiscale model of hepatitis C virus dynamics in plasma and liver following combination therapy
title_full_unstemmed	Multiscale model of hepatitis C virus dynamics in plasma and liver following combination therapy
title_sort	multiscale model of hepatitis c virus dynamics in plasma and liver following combination therapy
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/408653afc87f4315b2133467334bc8eb
work_keys_str_mv	AT xavierwootdetrixhe multiscalemodelofhepatitiscvirusdynamicsinplasmaandliverfollowingcombinationtherapy AT wojciechkrzyzanski multiscalemodelofhepatitiscvirusdynamicsinplasmaandliverfollowingcombinationtherapy AT anvermeulen multiscalemodelofhepatitiscvirusdynamicsinplasmaandliverfollowingcombinationtherapy AT juanjoseperezruixo multiscalemodelofhepatitiscvirusdynamicsinplasmaandliverfollowingcombinationtherapy
_version_	1718420005816631296

Multiscale model of hepatitis C virus dynamics in plasma and liver following combination therapy

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