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- Title
Developmental population pharmacokinetics-pharmacodynamics and dosing optimization of cefoperazone in children.
- Authors
Shi, Hai-Yan; Wang, Kai; Wang, Rong-Hua; Wu, Yue-E; Tang, Bo-Hao; Li, Xue; Du, Bin; Kan, Min; Zheng, Yi; Xu, Bao-Ping; Shen, A-Dong; Su, Le-Qun; Jacqz-Aigrain, Evelyne; Huang, Xin; Zhao, Wei
- Abstract
<bold>Objectives: </bold>To evaluate the population pharmacokinetics of cefoperazone in children and establish an evidence-based dosing regimen using a developmental pharmacokinetic-pharmacodynamic approach in order to optimize cefoperazone treatment.<bold>Methods: </bold>A model-based, open-label, opportunistic-sampling pharmacokinetic study was conducted in China. Blood samples from 99 cefoperazone-treated children were collected and quantified by HPLC/MS. NONMEM software was used for population pharmacokinetic-pharmacodynamic analysis. This study was registered at ClinicalTrials.gov (NCT03113344).<bold>Results: </bold>A two-compartment model with first-order elimination agreed well with the experimental data. Covariate analysis showed that current body weight had a significant effect on the pharmacokinetics of cefoperazone. Monte Carlo simulation showed that for bacteria for which cefoperazone has an MIC of 0.5 mg/L, 78.1% of hypothetical children treated with '40 mg/kg/day, q8h, IV drip 3 h' would reach the pharmacodynamic target. For bacteria for which cefoperazone has an MIC of 8 mg/L, 88.4% of hypothetical children treated with 80 mg/kg/day (continuous infusion) would reach the treatment goal. A 160 mg/kg/day (continuous infusion) regimen can cover bacteria for which cefoperazone has an MIC of 16 mg/L. Nevertheless, even if using the maximum reported dose of 160 mg/kg/day (continuous infusion), the ratio of hypothetical children reaching the treatment target was only 9.9% for bacteria for which cefoperazone has an MIC of 32 mg/L.<bold>Conclusions: </bold>For cefoperazone, population pharmacokinetics were evaluated in children and an appropriate dosing regimen was developed based on developmental pharmacokinetics-pharmacodynamics. The dose indicated in the instructions (20-160 mg/kg/day) can basically cover the clinically common bacteria for which cefoperazone has an MIC of ≤16 mg/L. However, for bacteria for which the MIC is >16 mg/L, cefoperazone is not a preferred choice.
- Subjects
CHINA; ANTIBIOTICS; RESEARCH; HIGH performance liquid chromatography; RESEARCH methodology; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; SYSTEM analysis; CEFOPERAZONE; MICROBIAL sensitivity tests
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2020, Vol 75, Issue 7, p1917
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkaa071