P04?Non-compartmental analysis of vancomycin pharmacokinetics in critically ill children

摘要

Background Vancomycin is often used as the drug of choice in the treatment of bacteria that are methicillin resistant or in patients sensitive to penicillin. This study describes the pharmacokinetics of vancomycin in critically ill children. Methods Children aged 1month to 16 years admitted to the paediatric intensive care unit of the Red Cross War Memorial Hospital and on vancomycin treatment for ≥24 hours and ≤72 hours were prospectively recruited. Blood samples were collected around predetermined optimal sampling times. A minimum of three samples per patients was analysed. Non-compartmental analysis was used to determine the volume of distribution (V), clearance (CL), half-life (tsub1/2/sub), area under the concentration-time curve (AUC), elimination constant (Ke) and Mean residence time (MRT). The minimum concentration (Cmin) and maximum concentration (Cmax) of vancomycin were measured directly as trough and peak plasma concentration respectively. Analysis of data was performed using PKNCA version 0.8.5 in R. Results Forty-nine serum concentrations from 10 patients were included in the analysis. The ratio of male to female was 1:1. Median age (Range) was 1.6 (0.2–15) years, weight = 10.6 (3.1–31.3) kg, baseline serum creatinine (Scr) = 0.31 (0.15–0.78) mg/dL. Patients received daily vancomycin doses ranging from 56 to 78 mg/kg. Mean PK parameters (range) were as follows: CL = 0.12±0.15 (0.018–0.52) L/h/kg, V =0.68±0.47 (0.15–1.57) L/kg, Ke = 0.147±0.073 (0.07–0.33) hsup-1/sup, tsub1/2/sub =5.54±2.03 (2.11–9.62) h, MRT=8.02±2.92 (3.04–13.88) h, AUC =322.07±245.65 (31.6–850.4) mg/L.h, Cmin =6.21±3.66 (2.0–14.5) mg, Cmax =38.91±31.92 (10.4–97.2) mg. Trough concentration and AUC were not met in 80% and 75% of the patients. Conclusion Variability in vancomycin pharmacokinetics was observed in patients. At current doses, target trough concentrations and AUC were not met.