RT Journal Article SR Electronic T1 Pharmacokinetics and dose requirements of vancomycin in neonates JF Archives of Disease in Childhood - Fetal and Neonatal Edition JO Arch Dis Child Fetal Neonatal Ed FD BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health SP F221 OP F227 DO 10.1136/fn.81.3.F221 VO 81 IS 3 A1 C Grimsley A1 A H Thomson YR 1999 UL http://fn.bmj.com/content/81/3/F221.abstract AB 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 effects 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.