The aim of this study was to characterize and validate the population pharmacokinetics of gentamicin in infants and to determine
the influences of clinically relevant covariates to explain the inter- and intraindividual variabilities associated with this
drug. Infants receiving intravenous gentamicin and with routine therapeutic drug monitoring were consecutively enrolled in the
study. Plasma concentration and time data were retrospectively collected from 208 infants (1 to 24 months old) of the Hospital
Universitario Severo Ochoa (Spain), of whom 44% were males (mean age [standard deviation], 5.84.8 months; mean body
weight, 6.42.2 kg). Data analysis was performed with NONMEM 7.2. One- and two-compartment open models were analyzed
to estimate the gentamicin population parameters and the influences of several covariates. External validation was carried out in
another population of 55 infants. The behavior of gentamicin in infants exhibits two-compartment pharmacokinetics, with total
body weight being the covariate that mainly influences central volume (Vc) and clearance (CL); this parameter was also related to
creatinine clearance. Both parameters are age related and different from those reported for neonatal populations. On the basis of
clinical presentation and diagnosis, a once-daily dosage regimen of 7 mg/kg of body weight every 24 h is proposed for intravenous
gentamicin, followed by therapeutic drug monitoring in order to avoid toxicity and ensure efficacy with minimal blood
sampling. Gentamicin pharmacokinetics and disposition were accurately characterized in this pediatric population (infants),
with the parameters obtained being different from those reported for neonates and children. These differences should be considered
in the dosing and therapeutic monitoring of this antibiotic.