Hai-Yan Shi1,2, Kai Wang3, Rong-Hua Wang4, Yue-E Wu2, Bo-Hao Tang2, Xue Li2, Bin Du2, Min Kan2, Yi Zheng2, Bao-Ping Xu5, A-Dong Shen6, Le-Qun Su1, Evelyne Jacqz-Aigrain7, Xin Huang1,2, Wei Zhao1,2. 1. Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan, China. 2. Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan, China. 3. Department of Paediatric Respiratory Cardiology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China. 4. Department of Pharmacy, The Affiliated Weihai Second Municipal Hospital of Qingdao University, Weihai, China. 5. China National Clinical Research Centre for Respiratory Diseases, Respiratory Department, Beijing Children's Hospital, Capital Medical University, National Centre for Children's Health, Beijing, China. 6. Beijing Key Laboratory of Paediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Centre for Respiratory Diseases, National Key Discipline of Paediatrics (Capital Medical University), Beijing Paediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Centre for Children's Health, Beijing, China. 7. Department of Paediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France.
Abstract
OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVES: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
Authors: Bin Du; Yue Zhou; Bo-Hao Tang; Yue-E Wu; Xin-Mei Yang; Hai-Yan Shi; Bu-Fan Yao; Guo-Xiang Hao; Dian-Ping You; John van den Anker; Yi Zheng; Wei Zhao Journal: Front Pharmacol Date: 2021-03-15 Impact factor: 5.810
Authors: Stef Schouwenburg; Robin F J van der Klip; Tim J L Smeets; Nicole G M Hunfeld; Robert B Flint; Matthijs de Hoog; Henrik Endeman; Birgit C P Koch; Enno D Wildschut; Alan Abdulla Journal: Ther Drug Monit Date: 2022-02-01 Impact factor: 3.118