Pharmacokinetics and dose requirements of vancomycin in neonates
C Grimsleya b, A H Thomsonb c
a Pharmacy Department
Yorkhill NHS Trust
Glasgow G3 8SJ, b Department
of Pharmaceutical Sciences University of
Strathclyde Glasgow, c Department of Medicine and
Therapeutics University of Glasgow
West Glasgow Hospitals Trust
Glasgow
Correspondence to: Ms Carol Grimsley. Email:a.h.thomson{at}clinmed.gla.ac.uk
Accepted 15 May 1999
AIMS
To design and
evaluate dosing guidelines for vancomycin based on data collected
during routine use of the drug.
METHODSFollowing 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.
RESULTSPostconceptual
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%.
CONCLUSIONSThe
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.
Keywords: vancomycin; population pharmacokinetics; guidelines
© 1999 by Archives of Disease in Childhood
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