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Population pharmacokinetics and dose optimization of ceftriaxone for children with community-acquired pneumonia

  • Pharmacokinetics and Disposition
  • Published:
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Abstract

Purpose

To assess ceftriaxone population pharmacokinetics in a large pediatric population and describe the proper dose for establishing an optimized antibiotic regimen.

Methods

From pediatric patients using ceftriaxone, blood samples were obtained and the concentration was measured using high-performance liquid chromatography ultraviolet detection. The NONMEM software program was used for population pharmacokinetic analysis, for which data from 99 pediatric patients (2 to 12 years old) was collected and 175 blood concentrations were obtained.

Results

The best fit with the data was shown by the one-compartment model with first-order elimination. According to covariate analysis, weight had a significant impact on the clearance of ceftriaxone. Using Monte Carlo simulation, in a pediatric population with community-acquired pneumonia, a dose regimen of 100 mg/kg every 24 h produced satisfactory target attainment rates while remaining within the required minimum inhibitory concentration (2 mg/L).

Conclusion

Population pharmacokinetics of ceftriaxone was evaluated in children and an optimum dosing regimen was constructed on the basis of the pharmacokinetics-pharmacodynamics model-based approach.

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Funding

This work was supported by the National Science and Technology Major Projects for “Major New Drugs Innovation and Development” (2017ZX09304029-002, 2017ZX09304029-005), Scientific Research Foundation for the High-Level Returned Overseas Chinese Scholars (Ministry of Human Resources and Social Security, CG2016030001) and Hundred-Talent Program (The People’s Government of Hebei Province, E2015100010), Young Taishan Scholars Program of Shandong Province, Qilu Young Scholar Program of Shandong University, and Science and Technology Planning Project of Hebei Province (15277705D), We declare that we have no conflicts of interest relevant to this article.

Author information

Author notes

  1. Li-Yuan Tian and Wei Zhao contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, No. 44, Wenhua West Road, Jinan, Shandong Province, China

    Muhammad Wasim Khan, Yue-E Wu, Bo-Hao Tang, Min Kan, Yi Zheng & Wei Zhao

  2. Department of Respiratory Care, Children’s Hospital of Hebei Province affiliated to Hebei Medical University, Shijiazhuang, China

    Ya-Kun Wang & Li-Yuan Tian

  3. Department of Clinical Pharmacy, Clinical Trial Center, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, China

    Hai-Yan Shi & Wei Zhao

  4. China National Clinical Research Center for Respiratory Diseases, Respiratory Department, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

    Bao-Ping Xu

  5. Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, China

    A-Dong Shen

  6. Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, APHP, Paris, France

    Evelyne Jacqz-Aigrain

  7. University Paris Diderot, Sorbonne Paris Cité, Paris, France

    Evelyne Jacqz-Aigrain

Authors
  1. Muhammad Wasim Khan
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Contributions

LYT, BPX, ADS, EJA, and WZ designed the study; YKW, YEW, and LYT organized the trial and recruited patients; MK, YZ, and HYS set up the analytical method; MWK, BHT, and WZ performed PK analysis; MWK, YKW, LYT, and WZ drafted the first version of the manuscript and it was critically reviewed by all the other authors.

Corresponding author

Correspondence to Wei Zhao.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

This study was conducted at the Children’s Hospital of Hebei Province and was approved by the ethics board of the Children’s Hospital of Hebei Province affiliated to Hebei Medical University. This study was also registered at ClinicalTrials.gov (NCT03113344).

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Khan, M.W., Wang, YK., Wu, YE. et al. Population pharmacokinetics and dose optimization of ceftriaxone for children with community-acquired pneumonia. Eur J Clin Pharmacol 76, 1547–1556 (2020). https://doi.org/10.1007/s00228-020-02939-4

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