Vancomycin pharmacokinetics and Bayesian estimation in pediatric patients

The vancomycin pharmacokinetic profile was characterized in six pediatric p atients and the potential of nonlinear mixed effects modeling and Bayesian forecasting for vancomycin monitoring was explored using NONMEM V (1.1). Ba sed on steady state serial vancomycin concentrations, the estimates of mean t(1/2), Vd, and CI derived by the Sawchuk and Zaske method(1) were 3.52 ho urs, 0.57 L/kg, and 0.12 Uh per kg, respectively. NONMEM analysis demonstra ted that a weight-adjusted two-compartment model described individual patie nts' data better than a comparable one-compartment model. The two-compartme nt estimates of mean t(1/2)alpha, t(1/2)beta, V-ss, and Cl were 0.80 hour, 5.63 hours, 0.63 L/kg, and 0.11 L/h per kg, respectively. The relatively lo ng mean t(1/2)alpha suggests that peak vancomycin concentrations measured e arlier than 4 hours postdose do not reflect postdistributional serum concen trations. NONMEM population modeling revealed that a weight-adjusted two-co mpartment model provided a better fit than a comparable one-compartment mod el. The resulting population parameters and variances were fixed in NONMEM to obtain Bayesian predictions of individual vancomycin serum concentration s. Bayesian estimation with either a single midinterval or trough sample ha s the potential to provide accurate and precise predictions of vancomycin c oncentrations. This should be evaluated using a vancomycin population pharm acokinetic model based on a larger sample of pediatric patients.