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.

Evaluation of Bayesian Predictability of Vancomycin Concentration Using Population Pharmacokinetic Parameters in Pediatric Patients

“…Wrishko et al also evaluated the predictive performance of VCM concentration in pediatric patients and showed that trough sampling alone could provide clinically acceptable predictions of VCM concentrations at other sam- pling points. 34) They also showed that a later sampling point improved the relative accuracy and precision of trough prediction. Theseˆndings coincide with our present results, although the compartment model used in each study is diŠerent.…”

Population Pharmacokinetics and Dosing Optimization of Vancomycin in Children with Malignant Hematological Disease

“…In children, the standard dose evaluation studies of antimicrobials are usually based on a "nonselected" pediatric population and do not take into account the potential impact of the disease and disease state, which are the main factors that ultimately influence drug exposure in the clinical setting (17). For the purposes of comparison, the demographics and pharmacokinetic parameters of vancomycin obtained from different pediatric studies (10,18,19) are summarized in Table 4. The magnitude of the differences provides strong argument for studying pharmacokinetics in selected subgroups of patients.…”

Current Recommended Dosing of Vancomycin for Children With Invasive Methicillin-Resistant Staphylococcus aureus Infections Is Inadequate

“…In this same study a weighted average of vancomycin CL from the three reported age groups (mean age of groups 3.9, 5.6, and 7.6 years) was calculated to obtain an overall mean vancomycin CL in children. The mean vancomycin CL for each study was: 0.114(15), 0.103(16), 0.157(17) and 0.110 L/hr/kg(18) respectively.…”

“…Four studies were identified in which vancomycin CL was calculated based on direct measures of vancomycin levels in children(15-18). In one study(17) a recalculated vancomycin CL was required to account for vancomycin infusion time (19), which had not been taken into account by the authors.…”