A vancomycin steady‐state trough concentration (
Cmin) of 15‐20 mg/L is recommended for achieving a ratio of the 24‐hour area under the curve to the minimum inhibitory concentration (AUC
0‐24/MIC) of ≥400 in adults. Since few paediatric data are available, our objectives were to (a) measure the
pharmacokinetic indices of vancomycin and (b) determine the correlation between
Cmin and AUC
0‐24/MIC in paediatric patients. Population‐based
pharmacokinetic modelling was performed for paediatric patients to estimate the individual parameters. The relationship between
Cmin and the calculated AUC
0‐24/MIC was explored using linear regression and a probabilistic framework. A sensitivity analysis was also conducted using Monte Carlo simulations. Body‐weight significantly influenced the
pharmacokinetics of vancomycin. Based on real data and simulations,
Cmin ranges of 5.0‐5.9 and 9.0‐12.9 mg/L were associated with AUC
0‐24/MIC ≥400 for MIC values of ≤0.5 and ≤1 mg/L, respectively. Vancomycin regimens of 10 and 15 mg/kg every 6 hours achieved a
Cmin of 5.0‐5.9 mg/L and AUC
0‐24/MIC ≥400 in >90% of the children when MIC was ≤0.5 mg/L. At a MIC of ≤1 mg/L, vancomycin at 15 mg/kg every 6 hours achieved
Cmin of 9.0‐12.9 mg/L and AUC
0‐24/MIC ≥400 in 2.0‐ and 1.6‐fold as many children compared to a dose of 10 mg/kg every 6 hours, respectively. Vancomycin
Cmin values of 5.0‐12.9 mg/L were strongly predictive of achieving AUC
0‐24/MIC ≥400, and rational dosing regimens of 10‐15 mg/kg q6h were required in paediatric patients, depending on the pathogen.
相似文献