Whole Body Physiologically Based Pharmacokinetic Model to Explain A Patient With Drug-Drug Interaction Between Voriconazole and Flucloxacillin.

ABSTRACT:

Background and objectives

Voriconazole administered concomitantly with flucloxacillin may result in subtherapeutic plasma concentrations as shown in a patient with Staphylococcus aureus sepsis and a probable pulmonary aspergillosis. After switching our patient to posaconazole, therapeutic concentrations were reached. The aim of this study was to first test our hypothesis that flucloxacillin competes with voriconazole not posaconazole for binding to albumin ex vivo, leading to lower total concentrations in plasma.

Methods

A physiologically based pharmacokinetic (PBPK) model was then applied to predict the mechanism of action of the drug-drug interaction (DDI). The model included non-linear hepatic metabolism and the effect of a severe infectious disease on cytochrome P450 (CY

SUBMITTER: Abdullah-Koolmees H 

PROVIDER: S-EPMC11549138 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature