Developmental population pharmacokinetics-pharmacodynamics and dosing optimization of cefoperazone in children.

The Journal of Antimicrobial Chemotherapy
Hai-Yan ShiWei Zhao

Abstract

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. 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). 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...Continue Reading

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Jan 31, 2018·Antimicrobial Agents and Chemotherapy·Zhong-Ren ShiWei Zhao
Nov 26, 2018·International Journal of Antimicrobial Agents·Hui QiA-Dong Shen

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Citations

Aug 14, 2020·The Journal of Antimicrobial Chemotherapy·Tom G JacobsUNKNOWN WHO Paediatric Antiretroviral Working Group

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