Modeling and Simulation as a Tool to Assess Voriconazole Exposure in the Central Nervous System.

ABSTRACT: Voriconazole is a triazole antifungal used empirically for the treatment of complicated meningitis associated with Cryptococcus neoformans. Biopsy studies show that the drug exhibits adequate brain penetration although levels of cerebral spinal fluid (CSF) are highly variable. Considering that CSF is one of the main surrogates for CNS exposure, the present work proposed the building of a population pharmacokinetic modeling (popPK) model able to describing the exposure achieved by voriconazole in the plasma, interstitial cerebral fluid and CSF of healthy and infected rats. The developed popPK model was described by four compartments, including total plasma, free brain and total CSF concentrations. The following PK parameters were determined: K_m = 4.76 mg/L, V_max

SUBMITTER: Staudt KJ 

PROVIDER: S-EPMC10384042 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature