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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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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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.
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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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DOI: https://doi.org/10.1038/s41390-023-02941-3