Vancomycin population pharmacokinetics in neonates

Background: Recently the value of vancomycin therapeutic drug monitoring, a s well as the required therapeutic range, has been subject of debate, resul ting in new recommendations, This study was performed to incorporate these new insights in an up-to-date dosing scheme far neonates of various gestati onal ages, Methods: In this retrospective study with prospective validation, 108 newbo rns with suspected central line-related septicemia during the first month o f life received 30 mg/kg/day vancomycin divided into two doses regardless o f gestational or postconceptional age, Trough and peak vancomycin serum con centrations were determined before and after the third dose. Vancomycin dat a were analyzed according to a one-compartment open model with use of NONME M population pharmacokinetic software, Model parameters were evaluated and then used to simulate vancomycin dosing for different dose and dose interva l combinations. Targets were a trough concentration between 5 and 15 mg/L a nd a peak below 40 mg/L, In the prospective study, the optimal scheme was t ested in 22 patients. Results: Of the 108 patients, 34.3% of measured trough concentrations and 1 7.6K of peak concentrations were outside the desired therapeutic range. The model that best fitted the data included clearance and volume per kilogram and was independent of gestational age, Simulation of various dosing schem es showed that a dosing schedule of 30 mg/kg/day; irrespective of gestation al age, in three doses was optimal, and this scheme was prospectively teste d, Mean trough concentrations before the second dose were 8.2 +/- 2.2 mg/L versus a predicted trough of 8.9 +/- 2.5 mg/L, No peak levels higher than 4 0 mg/L were found, Conclusions: The use of the proposed schedule leads to adequate vancomycin trough serum concentrations, and there is no need for routine monitoring of peak serum concentrations.