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Population pharmacokinetics of ciprofloxacin in newborns with early onset neonatal sepsis and suspected meningitis

Pediatric Research volume 95, pages 1273–1278 (2024)Cite this article

Abstract

Background

Neonatal Sepsis accounts for significant proportion of neonatal mortality globally. Ciprofloxacin can be used as an effective antimicrobial against common causative agents of neonatal sepsis. However, there is only limited information about its pharmacokinetic distribution in plasma and Cerebrospinal fluid (CSF) of neonates.

Methods

Plasma and CSF samples were taken using a sparse sampling technique from neonates who received at least one dose of intravenous ciprofloxacin. Ciprofloxacin levels were analysed using high-performance liquid chromatography (HPLC). Population pharmacokinetic analysis was conducted using a non-linear mixed-effects modelling using Pumas® (Pharmaceutical Modelling and Simulation) package (Version 2.0).

Results

53 neonates were enroled in the study of whom; 9 (17%) had meningitis. The median concentration of ciprofloxacin in CSF was 1.4 (0.94–2.06) ug/ml and plasma was 2.94 (1.8–5.0) ug/ml. A one-compartment model with first-order elimination fitted the data. Body weight was found to be a significant covariate on volume of distribution (Vd). Simulations based on the final model suggest that dose of 10 mg/kg, intravenous b.d may not be able to achieve the desirable indices.

Conclusions

One compartment model with weight as a covariate explained the available data. Further studies with modified sampling strategy, larger sample size and variable dose levels are needed.

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Fig. 1: Ciprofloxacin plasma concentrations versus time for all included individuals.
Fig. 2: Observation data versus population predictions (up left) and versus individual predictions (up right) in the final model.
Fig. 3: Visual predictive check plot.
Fig. 4: Scatter plot distribution of CCSF/ Cplasma in relation to neonates with and without meningitis.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Author notes

  1. These authors jointly supervised this work: Kunal Garg, Ritika Kondel Bhandari.

Authors and Affiliations

  1. Department of Neonatology, Government Medical College and Hospital, Chandigarh, India

    Kunal Garg, Suksham Jain, Deepak Chawla & Supreet Khurana

  2. Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Ritika Kondel Bhandari & Nusrat Shafiq

  3. Department of Biochemistry, Government Medical College and Hospital, Chandigarh, India

    Shivani Jaswal

  4. Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India

    Surulivelrajan Mallayasamy & Jaya Shree Dilli Batcha

Authors
  1. Kunal Garg
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  2. Ritika Kondel Bhandari
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  4. Suksham Jain
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  8. Supreet Khurana
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Contributions

K.G. for writing the initial draft, RKB for analysis and re-review of manuscript along with N.S., N.S. for conceptualizing designing, planning and manuscript writing; pharmacokinetic modelling and preparation of manuscript; S.K.M. for data analysis and critical review of manuscript; D.C. for data analysis and critical review of manuscript; S.J. for biochemical sample separation and storage, M.S.R. for giving expert view on pharmacokinetic modelling; S.K. for conceptualisation of study, writing, data analysis and critical review of manuscript; J.D.B. for assisting in pharmacokinetic modelling.

Corresponding author

Correspondence to Supreet Khurana.

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Competing interests

The authors declare no competing interests.

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Consent was taken from either of parent’s before enroling neonate in the study.

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Garg, K., Bhandari, R.K., Shafiq, N. et al. Population pharmacokinetics of ciprofloxacin in newborns with early onset neonatal sepsis and suspected meningitis. Pediatr Res 95, 1273–1278 (2024). https://doi.org/10.1038/s41390-023-02941-3

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