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Desired vancomycin trough concentration to achieve an AUC 0‐24 /MIC ≥400 in Chinese children with complicated infectious diseases
Author(s) -
Zhang Tao,
Cheng Hua,
Pan Zhenyu,
Mi Jie,
Dong Yuzhu,
Zhang Ying,
Sun Dan,
Du Qian,
Cheng Xiaoliang,
Dong Yalin
Publication year - 2020
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.13303
Subject(s) - cmin , vancomycin , pharmacokinetics , medicine , minimum inhibitory concentration , trough concentration , therapeutic drug monitoring , population , pharmacology , antibiotics , cmax , microbiology and biotechnology , biology , staphylococcus aureus , environmental health , bacteria , genetics
A vancomycin steady‐state trough concentration ( C min ) 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 C min 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 C min 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, C min 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 C min 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 C min 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 C min 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.