Pharmacokinetics and dose requirements of vancomycin in neonates
- aPharmacy Department Yorkhill NHS Trust Glasgow G3 8SJ, bDepartment of Pharmaceutical Sciences University of Strathclyde Glasgow, cDepartment of Medicine and Therapeutics University of Glasgow West Glasgow Hospitals Trust Glasgow
- Ms Carol Grimsley. Email:a.h.thomson{at}clinmed.gla.ac.uk
- Accepted 15 May 1999
Abstract
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.
