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JAC Advance Access published online on June 16, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl244
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received November 4, 2005
Revised May 12, 2006
Accepted May 22, 2006

Original article

Population pharmacokinetics of gentamicin in premature newborns

Benito García 1, Emilia Barcia 2 *, Fernando Pérez 3, and Irene T. Molina 2

1 Pharmacy Service, Hospital Severo Ochoa, Leganés, Spain
2 Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University Complutense of Madrid, Spain
3 Pediatric Service, Hospital Severo Ochoa, Leganés, Spain

* To whom correspondence should be addressed.
Emilia Barcia, E-mail: ebarcia{at}farm.ucm.es


  Abstract

Objectives: To determine the pharmacokinetic parameters of gentamicin in a population of 200 premature newborns and to investigate the influence of several clinical and physiopathological covariates on the pharmacokinetics of the drug. To validate the pharmacokinetic analysis performed in another population of 50 premature newborns.

Methods: A total of 200 premature newborns were evaluated at the neonatal intensive care unit of Severo Ochoa Hospital (Madrid, Spain). Four hundred and seventeen serum drug concentrations were included. Mean gestational age (GA) was 32.19 ± 2.97 weeks, mean postnatal age (PNA) was 5.49 ± 5.41 days and mean body weight (BW) was 1.68 ± 0.63 kg. Fifty additional newborns were studied for validation (mean GA 32.62 ± 3.07 weeks, mean PNA 5.17 ± 3.77 days and mean BW 1.80 ± 0.67 kg). Dosing, serum gentamicin concentrations and 15 covariates were collected. Data analysis was performed with NONMEM. One- and two-compartment open models were evaluated. Four parameters were analysed with the two-compartment open model: clearance (CL), central volume (Vc), peripheral volume (Vp) and intercompartmental clearance (Q).

Results and conclusions: The two-compartment open model was found to significantly better describe gentamicin pharmacokinetics in the neonate. More than PNA or GA, creatinine clearance (CLCR) plays an important role in the elimination of gentamicin in premature newborns. Creatinine clearance is also related to GA. The appropriate dosing regimens given in accordance with the characteristics of the patients are 5 mg/kg/48 h and 4 mg/kg/24 or 36 h for neonates <32 weeks and ≥32 weeks of GA, respectively.

Keywords: NONMEM; aminoglycosides; neonates.
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