New vancomycin dosage guidelines have been developed that achieve trough concentrations of 10-15 mg/L earlier and more consistently than current guidelines.

Aims-To design and evaluate dosing guidelines for vancomycin based on data collected during routine use of the drug. Methods-Following the observation that 66% of neonatal vancomycin trough concentrations were outside the target range, new dose guidelines were developed using a population pharmacokinetic approach. NONMEM (non-linear mixed eVects model) was used to analyse dose histories and 347 concentration measurements collected during routine therapeutic drug monitoring in 59 neonates. Results-Postconceptual ages in the patient group ranged from 26-45 weeks, weights from 0.57-4.23 kg, and creatinine concentrations from 18-172 µmol/l. The population estimate of vancomycin clearance (l/h/kg) was 3.56/creatinine concentration (µmol/l) with an interpatient coefficient of variation (CV) of 22% and volume of distribution 0.67 l/kg with a CV of 18%. Residual error was 4.5 mg/l. When the new recommendations on dosing were used prospectively in a separate group of neonates the proportion of acceptable troughs increased from 33% to 72%. Conclusions-The pharmacokinetics of vancomycin in neonates and young infants depend on weight and serum creatinine. Preliminary results from the new guidelines indicate an improvement on previous practice, but also an ongoing need to monitor concentrations. (Arch Dis Child Fetal Neonatal Ed 1999;81:F221-F227)