Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Why population pharmacokinetic studies are instrumental to boost clinical research in neonates, and suggestions on how clinicians should assess these papers

Pediatric Research volume 95, pages 1181–1183 (2024)Cite this article

A paper on the population pharmacokinetics of ciprofloxacin in newborns with early-onset neonatal sepsis and suspected meningitis has recently been published in this journal.1 The authors hereby mainly intended to quantify the pharmacokinetics of ciprofloxacin in the plasma and the cerebrospinal fluid compartment of neonates. This obviously has compound-specific, clinical relevance in the event of suspected or proven meningitis. However, we rather wanted to comment and reflect on the methodology applied, i.e., population pharmacokinetics, and why this research tool is relevant.

This methodology has occasionally been reported in papers on neonatal pharmacokinetics (i.c. ciprofloxacin, theophylline, caffeine, doxapram) recently published in this journal.1,2,3,4 At least as relevant to the readership, clinical researchers should be aware that this methodology holds the promise to be instrumental in making clinical research on pharmacokinetics more feasible. Furthermore, we felt that some suggestions on how to read and assess these papers are valuable for colleagues involved in developing neonatal formularies and clinicians who have to make bedside dosing decisions for their patients.5 Interested readers in search of a broader scope on the safety, dosing, and pharmaceutical quality for studies that evaluate drugs in neonates are referred to a review initiated by the International Neonatal Consortium (INC), and published in this journal.5

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Schematic comparison of population data analyses.

References

  1. Kunal, G. et al. Population pharmacokinetics of ciprofloxacin in newborns with early onset neonatal sepsis and suspected meningitis. Pediatr. Res. https://doi.org/10.1038/s41390-023-02941-3 (2023).

  2. Lim, S. Y., May, C. B., Johnson, P. N. & Miller, J. L. Caffeine dosing in premature neonates: impact of birth weight on a pharmacokinetic simulation study. Pediatr. Res. 93, 696–700 (2023).

    Article  CAS  PubMed  Google Scholar 

  3. Flint, R. B. et al. The bioavailability and maturing clearance of doxapram in preterm infants. Pediatr. Res. 89, 1268–1277 (2021).

    Article  CAS  PubMed  Google Scholar 

  4. Frymoyer, A. et al. Theophylline dosing and pharmacokinetics for renal protection in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia. Pediatr. Res. 88, 871–877 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ward, R. M. et al. Safety, dosing, and pharmaceutical quality for studies that evaluate medicinal products (including biological products) in neonates. Pediatr. Res. 81, 692–711 (2017).

    Article  PubMed  Google Scholar 

  6. Schouwenburg, S. et al. Review of scavenged sampling for sustainable therapeutic drug monitoring: do more with less. Ther. Drug Monit. 44, 215–223 (2022).

    Article  PubMed  Google Scholar 

  7. De Cock, R. F. et al. A neonatal amikacin covariate model can be used to predict ontogeny of other drugs eliminated through glomerular filtration in neonates. Pharm. Res. 31, 754–767 (2014).

    Article  PubMed  Google Scholar 

  8. Zhao, W. et al. External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings. Br. J. Clin. Pharm. 75, 1068–1080 (2013).

    Article  CAS  Google Scholar 

  9. Allegaert, K. et al. Covariates of tramadol disposition in the first months of life. Br. J. Anaesth. 100, 525–532 (2008).

    Article  CAS  PubMed  Google Scholar 

  10. Mahoney, L. et al. Grading the level of evidence of neonatal pharmacotherapy: midazolam and phenobarbital as examples. Pediatr. Res. https://doi.org/10.1038/s41390-023-02779-9 (2023).

Download references

Acknowledgements

Besides the affiliations mentioned, Karel Allegaert is appointed as Honorary Guest Professor at Henan, Zhengzhou Children’s Hospital (2023–2028).

Author information

Authors and Affiliations

  1. GCP office, Children’s Hospital Affiliated to Zhengzhou University, 450018, Zhengzhou, China

    Yan Li

  2. Department of Pharmacy, Children’s Hospital Affiliated to Zhengzhou University, 450018, Zhengzhou, China

    Yan Li

  3. Department of Development and Regeneration, KU Leuven, Leuven, Belgium

    Karel Allegaert

  4. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium

    Karel Allegaert

  5. Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands

    Karel Allegaert

Authors
  1. Yan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karel Allegaert
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors contributed to the commentary and agreed on the final version of the paper.

Corresponding author

Correspondence to Karel Allegaert.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Y., Allegaert, K. Why population pharmacokinetic studies are instrumental to boost clinical research in neonates, and suggestions on how clinicians should assess these papers. Pediatr Res 95, 1181–1183 (2024). https://doi.org/10.1038/s41390-023-03011-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-023-03011-4

Search

Advanced search

Quick links