Abstract
Fluconazole is used to treat hematogenous
Candida
meningoencephalitis in preterm and term infants. To characterize plasma and central nervous system exposure, an adult fluconazole physiologically‐based pharmacokinetic (PBPK) model was scaled to infants, accounting for age dependencies in glomerular filtration and metabolism. The model was optimized using 760 plasma samples from 166 infants (median postmenstrual age (range) 28 weeks (24–50)) and 27 cerebrospinal fluid (
CSF
) samples from 22 infants (
postmenstrual age
28 weeks (24–33)). Simulations evaluated achievement of the surrogate efficacy target of area under the unbound concentration‐time curve ≥ 400 mg • hour/L over the dosing interval in plasma and
CSF
using dosing guidelines. Average fold error of predicted concentrations was 0.73 and 1.14 for plasma and
CSF
, respectively. Target attainment in plasma and
CSF
was reached faster after incorporating a loading dose of 25 mg/kg.
PBPK
modeling can be useful in exploring
CNS
kinetics of drugs in children.
