Vancomycin pharmacokinetics and Bayesian estimation in pediatric patients

Ther Drug Monit. 2000 Oct;22(5):522-31. doi: 10.1097/00007691-200010000-00004.

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.

MeSH terms

  • Anti-Bacterial Agents / pharmacokinetics*
  • Bayes Theorem
  • Child
  • Child, Preschool
  • Cohort Studies
  • Drug Monitoring* / methods
  • Female
  • Humans
  • Male
  • Vancomycin / pharmacokinetics*

Substances

  • Anti-Bacterial Agents
  • Vancomycin