A Minimal Physiologically Based Pharmacokinetic Model to Characterize CNS Distribution of Metronidazole in Neuro Care ICU Patients.

ABSTRACT: Understanding antibiotic concentration-time profiles in the central nervous system (CNS) is crucial to treat severe life-threatening CNS infections, such as nosocomial ventriculitis or meningitis. Yet CNS distribution is likely to be altered in patients with brain damage and infection/inflammation. Our objective was to develop a physiologically based pharmacokinetic (PBPK) model to predict brain concentration-time profiles of antibiotics and to simulate the impact of pathophysiological changes on CNS profiles. A minimal PBPK model consisting of three physiological brain compartments was developed from metronidazole concentrations previously measured in plasma, brain extracellular fluid (ECF) and cerebrospinal fluid (CSF) of eight brain-injured patients. Volumes and blood flows were fixed t

SUBMITTER: Chauzy A 

PROVIDER: S-EPMC9598284 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature