Development of a physiologically-based pharmacokinetic pediatric brain model for prediction of cerebrospinal fluid drug concentrations and the influence of meningitis.

ABSTRACT: Different pediatric physiologically-based pharmacokinetic (PBPK) models have been described incorporating developmental changes that influence plasma drug concentrations. Drug disposition into cerebrospinal fluid (CSF) is also subject to age-related variation and can be further influenced by brain diseases affecting blood-brain barrier integrity, like meningitis. Here, we developed a generic pediatric brain PBPK model to predict CSF concentrations of drugs that undergo passive transfer, including age-appropriate parameters. The model was validated for the analgesics paracetamol, ibuprofen, flurbiprofen and naproxen, and for a pediatric meningitis population by empirical optimization of the blood-brain barrier penetration of the antibiotic meropenem. Plasma and CSF drug concentrations deriv

SUBMITTER: Verscheijden LFM 

PROVIDER: S-EPMC6592555 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature