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

Nathan P. Wiederhold

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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.

Original languageEnglish (US)
JournalClinical Pharmacology: Advances and Applications
Volume8
DOIs
StatePublished - Dec 23 2015

Keywords

  • Antifungal prophylaxis
  • Delayed-release tablet
  • Pharmacokinetics
  • Posaconazole
  • Posaconazole oral suspension

ASJC Scopus subject areas

  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections'. Together they form a unique fingerprint.

Cite this