Wei Zhao 1,2, Emmanuel Lopez 3, Valérie Biran 4, Xavier Durrmeyer 5, May Fakhoury 1, Evelyne Jacqz-Aigrain 1,2
1. Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, Université Paris Diderot, Assistance Publique - Hôpitaux de Paris, Paris, France 2. Clinical Investigation Center CIC9202, INSERM, Paris, France 3. Department of Neonatology, Groupe Hospitalier Cochin-Broca-Hotel Dieu, Université Paris Descartes, Assistance Publique - Hôpitaux de Paris, Paris, France 4. Department of Neonatology, Hôpital Robert Debré, Université Paris Diderot, Assistance Publique - Hôpitaux de Paris, Paris, France 5. Department of Neonatology, Hôpital Henri Mondor, Université Paris-Est Créteil, Assistance Publique - Hôpitaux de Paris, Créteil, France
Objective: Pharmacokinetic data are limited for vancomycin continuous infusion in neonates. Different dosing regimens were currently used in routine. The aim of this work is to evaluate the likelihood of achieving the targeted concentration with currently used dosing regimens and to optimize vancomycin therapy in neonates
Methods: Vancomycin concentrations during routine TDM were collected prospectively from neonates receiving vancomycin continuous infusion in 3 hospitals. Vancomycin concentrations were compared among the different dosage regimens and the relationship with age, weight and renal function was evaluated. The population was developed based on TDM results using NONMEM software. The dosing regimen was then optimized using developed model.
Results: Two hundred and seven concentrations were obtained from 116 neonates. Preterm neonates presented larger variability than term neonates. TDM results demonstrated that the risk of underdosing (<15 mg/L) and overdosing (>25 mg/L) were 26% and 27%, respectively. The loading dose strategy presented fewer neonates with subtherapeutic levels. The uniform weight-normalized dosage regimen (mg/kg) was not suitable for the whole neonatal period. A one-compartment model was then developed. The covariate analysis identified birth weight, current weight, postnatal age and serum creatinine as significant predictors of vancomycin dosing. The model evaluation supported the predictive performance of developed model. The model-based dosing regimen achieved the target concentrations in typical neonates (preterm, median and term) and simulated clinical trials.
Conclusions: The loading dose strategy with consideration of the baby’s birth weight, current weight, postnatal age and serum creatinine could be used in routine to individualize vancomycin continuous infusion therapy in neonates.
Reference: PAGE 21 () Abstr 2590 [www.page-meeting.org/?abstract=2590]
Poster: Paediatrics