Evaluatie van doseerrichtlijnen en populatiefarmacokinetiek van vancomycine bij kinderen met kanker.

BACKGROUND Vancomycin is standard therapy in pediatric oncology patients with neutropenic fever. In a previous study we showed that with a starting dose of 60 mg/kg/day in four doses 58% of patients had inadequate trough levels. As a result the starting dose was increased to 90 mg/kg/day. OBJECTIVE To determine whether a starting dose of 90 mg/kg/day in four doses leads to a higher percentage therapeutic trough levels compared to 60 mg/kg/day in four doses. Furthermore, population pharmacokinetics were described in pediatric oncology patients. DESIGN AND METHODS Prospective data from the VANCOPOP study were combined with retrospective data from the Academisch Medisch Centrum, Amsterdam. The percentage therapeutic trough levels (10-15 mg/L) in the first three days of therapy was the primary endpoint. As a secondary endpoint, renal toxicity was evaluated. Population pharmacokinetics were described using nonlinear mixed-effects modelling. RESULTS Data was available from 53 and 22 patients receiving 60 and 90 mg/kg/day, respectively. The percentages therapeutic trough concentrations were comparable in both groups (21% and 23%, respectively). The percentages sub- (68% and 41%, respectively) and supratherapeutic concentrations (12% and 36%, respectively) were different between dosing groups (p < 0.05). The population pharmacokinetics of vancomycin were described by a two-compartment model with creatinine clearance significantly affecting clearance. Based on Monte Carlo simulations the following doses were proposed: younger than two years 90 mg/kg/day, two till six years 80 mg/kg/day, six till twelve years 70 mg/kg/day and twelve till eighteen years 60 mg/kg/day, all in four doses. CONCLUSION Vancomycin clearance is age-dependent and highly variable in pediatric oncology patients. A prospective study is necessary to evaluate the proposed dosing guidelines for different age groups. [ABSTRACT FROM AUTHOR]