Pharmacokinetics and dose requirements of vancomycin in neonates

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 co ncentrations were outside the target range, new dose guidelines were develo ped using a population pharmacokinetic approach. NONMEM (non-linear mixed e ffects model) was used to analyse dose histories and 347 concentration meas urements collected during routine therapeutic drug monitoring in 59 neonate s. Results-Postconceptual ages in the patient group ranged from 26-45 weeks, w eights from 0.57-4.23 kg, and creatinine concentrations from 18-172 mu mol/ l. The population estimate of vancomycin clearance (1/h/kg) was 3.56/creati nine concentration (mu mol/l) with an interpatient coefficient of variation (CV) of 22% and volume of distribution 0.67 l/kg with a CV of 18%. Residua l error was 4.5 mg/l. When the new recommendations on dosing were used pros pectively in a separate group of neonates the proportion of acceptable trou ghs increased from 33% to 72%. Conclusions-The pharmacokinetics of vancomycin in neonates and young infant s depend on weight and serum creatinine. Preliminary results from the new g uidelines indicate an improvement on previous practice, but also an ongoing need to monitor concentrations.