Population Pharmacokinetics of Gentamicin in Preterm and Term Newborn Infants
Nielsen, Elisabet I(1), Uwe Ewald (2), Lena E Friberg (1)
(1) Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy, Uppsala University, Sweden; (2) Department of Neonatology, University Children’s Hospital, Uppsala, Sweden
Objectives: Gentamicin is an aminoglycoside antibiotic commonly used in the prophylaxis and treatment of gram negative infections in the neonatal population. Gentamicin is eliminated almost exclusively by glomerular filtration, and changes in gentamicin clearance (CL) in the neonate are likely to correlate with the functional maturation of the glomerular filtration rate. The aim of the present study was to describe the population pharmacokinetics (PK) of gentamicin in preterm and term newborn infants and to identify predictive covariates relevant for new improved dosing regimens. A second aim was to evaluate cystatin C (CysC) as a marker for renal function in the neonatal population.
Methods: A total of 592 plasma concentrations from 42 neonates (4-33 samples per subject) were collected in a prospective clinical trial performed at the neonatal intensive care unit, University Children’s Hospital,
Results: A two-compartment model with a combined additive and proportional residual error model described the gentamicin PK in the neonates. Inter individual variability (IIV) was significant for clearance and central volume of distribution (V1). Body weight was included as the primary covariate according to an allometric power model. GA and PNA were significant covariates for CL and inclusion resulted in a reduction in the unexplained IIV. No significant covariates besides BW were found for V1 or for the other parameters.
1. Larsson A, et al. Scand J Clin Lab Invest 2004; 64: 25-30