Population pharmacokinetic analysis of vancomycin in neonates. A new proposal of initial dosage guideline
- 24 June 2010
- journal article
- Published by Wiley in British Journal of Clinical Pharmacology
- Vol. 70 (5), 713-720
- https://doi.org/10.1111/j.1365-2125.2010.03736.x
Abstract
To determine the population pharmacokinetic parameters of vancomycin in neonatal patients with a wide range of gestational age and birth weight, and subsequently to design an initial dosing schedule for vancomycin in neonates. Using nonlinear mixed-effects modelling (NONMEM VI), the pharmacokinetics of vancomycin were investigated in 70 neonates with postmenstrual age and body weight ranging 25.1-48.1 weeks and 0.7-3.7kg, respectively. A one-compartment linear disposition model with zero order input and first-order elimination was used to describe the data. Nine demographic characteristics and 21 co-administered drugs were evaluated as covariates of clearance (CL) and distribution volume (V(d) ) of vancomycin. Weight-normalized clearance of vancomycin was influenced by postmenstrual age (PMA) and co-administration of amoxicillin-clavulanic acid. Weight-normalized volume of distribution was influenced by co-administration of spironolactone. CL and V(d) of the typical individual in this study population (PMA = 34.6 weeks, weight = 1.7kg) were estimated to be 0.066lh(-1) kg(-1) (95% CI 0.059, 0.073lh(-1) kg(-1) ) and 0.572lkg(-1) (95% CI 0.505, 0.639lkg(-1) ), respectively. This model was used to predict a priori serum vancomycin concentrations in a validation group (n= 41), which were compared with observed concentrations to determine the predictive performance of the model. The 95% confidence interval of mean prediction error included zero for both peak and trough vancomycin concentrations. Postmenstrual age, co-administration of amoxicillin-clavulanic acid and spironolactone have a significant effect on the weight-normalized CL and V(d) . An initial dosage guideline for vancomycin is proposed for preterm and full-term neonates, whereas the population pharmacokinetic model can be used for dosage individualization of vancomycin.This publication has 23 references indexed in Scilit:
- Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearanceBritish Journal of Clinical Pharmacology, 2006
- INTERACTIONS OF AMOXICILLIN AND CEFACLOR WITH HUMAN RENAL ORGANIC ANION AND PEPTIDE TRANSPORTERSDrug Metabolism and Disposition, 2006
- Population Pharmacokinetics of Arbekacin, Vancomycin, and Panipenem in NeonatesAntimicrobial Agents and Chemotherapy, 2004
- VancomycinClinical Pharmacokinetics, 2004
- Dose regimen for vancomycin not needing serum peak levels?Archives of Disease in Childhood: Fetal & Neonatal, 2002
- Influence of Pharmacokinetic Model on Vancomycin Peak Concentration TargetsTherapeutic Drug Monitoring, 1996
- Vancomycin Pharmacokinetics and Dosing in Premature NeonatesTherapeutic Drug Monitoring, 1995
- Bayesian Forecasting of Serum Vancomycin Concentrations in Neonates and InfantsTherapeutic Drug Monitoring, 1995
- Population pharmacokinetics of vancomycin in neonatesClinical Pharmacology & Therapeutics, 1994
- Some suggestions for measuring predictive performanceJournal of Pharmacokinetics and Biopharmaceutics, 1981