Article date: November 2010
By: María‐Remedios Marqués‐Miñana, Anas Saadeddin, José‐Esteban Peris, in Volume 70, Issue 5, pages 713-720
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
AIM
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.
METHODS
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 0.7–3.7 kg, 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 (Vd) of vancomycin.
RESULTS
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 Vd of the typical individual in this study population (PMA = 34.6 weeks, weight = 1.7 kg) were estimated to be 0.066 l h−1 kg−1 (95% CI 0.059, 0.073 l h−1 kg−1) and 0.572 l kg−1 (95% CI 0.505, 0.639 l kg−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.
CONCLUSIONS
Postmenstrual age, co‐administration of amoxicillin‐clavulanic acid and spironolactone have a significant effect on the weight‐normalized CL and Vd. 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.
DOI: 10.1111/j.1365-2125.2010.03736.x
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