title: Vancomycin pharmacokinetics and Bayesian estimation in pediatric patients.
abstract: The vancomycin pharmacokinetic profile was characterized in six pediatric patients and the potential of nonlinear mixed effects modeling and Bayesian forecasting for vancomycin monitoring was explored using NONMEM V (1.1). Based on steady state serial vancomycin concentrations, the estimates of mean t1/2, Vd, and Cl derived by the Sawchuk and Zaske method (1) were 3.52 hours, 0.57 L/kg, and 0.12 L/h per kg, respectively. NONMEM analysis demonstrated that a weight-adjusted two-compartment model described individual patients' data better than a comparable one-compartment model. The two-compartment estimates of mean t1/2alpha, t1/2beta, Vss, and Cl were 0.80 hour, 5.63 hours, 0.63 L/kg, and 0.11 L/h per kg, respectively. The relatively long mean t1/2alpha suggests that peak vancomycin concentrations measured earlier than 4 hours postdose do not reflect postdistributional serum concentrations. NONMEM population modeling revealed that a weight-adjusted two-compartment model provided a better fit than a comparable one-compartment model. The resulting population parameters and variances were fixed in NONMEM to obtain Bayesian predictions of individual vancomycin serum concentrations. Bayesian estimation with either a single midinterval or trough sample has the potential to provide accurate and precise predictions of vancomycin concentrations. This should be evaluated using a vancomycin population pharmacokinetic model based on a larger sample of pediatric patients.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
authors.forename: R E
authors.initials: RE
authors.lastname: Wrishko
authors.forename: M
authors.initials: M
authors.lastname: Levine
authors.forename: D
authors.initials: D
authors.lastname: Khoo
authors.forename: P
authors.initials: P
authors.lastname: Abbott
authors.forename: D
authors.initials: D
authors.lastname: Hamilton
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001499:Bayes Theorem; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D014640:Vancomycin / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin