Journal Article

Pharmacokinetic basis for the use of extended interval dosage regimens of gentamicin in neonates

José M. Lanao, Mª Victoria Calvo, José Antonio Mesa, Ana Martín-Suárez, Mª Teresa Carbajosa, Francisco Miguelez and Alfonso Domínguez-Gil

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 54, issue 1, pages 193-198
Published in print July 2004 | ISSN: 0305-7453
Published online July 2004 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkh261
Pharmacokinetic basis for the use of extended interval dosage regimens of gentamicin in neonates

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Objectives: To analyse the pharmacokinetic basis for the use of extended-interval dosage regimens of gentamicin in neonates using population pharmacokinetics.

Patients and methods: The population pharmacokinetics of gentamicin was studied retrospectively in a population of 113 neonates divided into two groups: one for computing the population model (n=97) and another for validation (n=36). A one-compartment pharmacokinetic model and non-linear mixed-effects modelling were used to assess the population pharmacokinetic model.

Results: Weight (W) and postnatal age (PA) were the covariates that influenced the pharmacokinetic parameters of gentamicin. The final population model obtained was: distribution volume, V (L)=0.636 × W (kg)0.852; clearance, Cl (L/h)=0.032 × W (kg)1.482+0.0024 × PA (days). The predictive performance of the model in the population validation was adequate for clinical purposes. The optimized population model allowed us to simulate gentamicin serum levels and their variability, in this kind of patient, when extended-interval dosage administration regimens were implemented.

Conclusions: According to our pharmacokinetic population model, initial doses of gentamicin of 10 mg/kg, and dosage intervals between 36–48 h, appear to be appropriate to achieve target peak and trough serum levels of 15–20 and <0.5 mg/L, respectively, when extended-interval dosage regimens are implemented in newborns. The half-life of gentamicin in premature babies of very low weight and gestational age <31 weeks is long. Thus, to achieve serum concentrations in the 1–10 mg/L range, the use of dosage regimens of 5 mg/kg at 36–48 h dosage intervals seems suitable.

Keywords: population pharmacokinetics; extended-interval dosage regimens; aminoglycosides

Journal Article.  3687 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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