JAC Advance Access published online on May 18, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh261
© 2004 by The British Society for Antimicrobial Chemotherapy
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1 Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University Hospital, University of Salamanca, Salamanca, Spain
* To whom correspondence should be addressed. E-mail: jmlanao{at}usal.es.
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 x W (kg)0.852; clearance, Cl (L/h)=0.032 x W (kg)1.482+0.0024 x 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.
Revised March 5, 2004
Accepted April 4, 2004
Original article
Pharmacokinetic basis for the use of extended interval dosage regimens of gentamicin in neonates
2 Department of Pharmacy Service, University Hospital, University of Salamanca, Salamanca, Spain
3 Department of Neonatology Unit, Pediatrics Service, University Hospital, University of Salamanca, Salamanca, Spain
4 Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University Hospital, University of Salamanca, Salamanca, Spain; Department of Pharmacy Service, University Hospital, University of Salamanca, Salamanca, Spain
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