Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections

Nathan P Wiederhold Departments of Pathology and Medicine/Infectious Diseases, University of Texas Health Science Center at San Antonio, South Texas Reference Laboratories, San Antonio, TX, USA Abstract: Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various...

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Autor principal:	Wiederhold NP
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Posaconazole pharmacokinetics delayed release tablet Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/15e67c350ada42bda555c30ac0557085
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spelling	oai:doaj.org-article:15e67c350ada42bda555c30ac05570852021-12-02T00:06:21ZPharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections1179-1438https://doaj.org/article/15e67c350ada42bda555c30ac05570852015-12-01T00:00:00Zhttps://www.dovepress.com/pharmacokinetics-and-safety-of-posaconazole-delayed-release-tablets-fo-peer-reviewed-article-CPAAhttps://doaj.org/toc/1179-1438Nathan P Wiederhold Departments of Pathology and Medicine/Infectious Diseases, University of Texas Health Science Center at San Antonio, South Texas Reference Laboratories, San Antonio, TX, USA Abstract: Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data regarding clinical efficacy are needed. Keywords: posaconazole, pharmacokinetics, delayed-release tablet, antifungal prophylaxis, posaconazole oral suspensionWiederhold NPDove Medical PressarticlePosaconazolepharmacokineticsdelayed release tabletTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol 2016, Iss Issue 1, Pp 1-8 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Posaconazole pharmacokinetics delayed release tablet Therapeutics. Pharmacology RM1-950
spellingShingle	Posaconazole pharmacokinetics delayed release tablet Therapeutics. Pharmacology RM1-950 Wiederhold NP Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections
description	Nathan P Wiederhold Departments of Pathology and Medicine/Infectious Diseases, University of Texas Health Science Center at San Antonio, South Texas Reference Laboratories, San Antonio, TX, USA Abstract: Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data regarding clinical efficacy are needed. Keywords: posaconazole, pharmacokinetics, delayed-release tablet, antifungal prophylaxis, posaconazole oral suspension
format	article
author	Wiederhold NP
author_facet	Wiederhold NP
author_sort	Wiederhold NP
title	Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections
title_short	Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections
title_full	Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections
title_fullStr	Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections
title_full_unstemmed	Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections
title_sort	pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/15e67c350ada42bda555c30ac0557085
work_keys_str_mv	AT wiederholdnp pharmacokineticsandsafetyofposaconazoledelayedreleasetabletsforinvasivefungalinfections
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Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections

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