Population pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing regimens

Abstract

Purpose

This study aimed to characterize pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing scheme.

Methods

Children treated with ciprofloxacin were included. Pharmacokinetics were described using non-linear mixed-effect modelling and validated with an external dataset. Monte Carlo simulations investigated dosing regimens to achieve a target AUC0-24 h/MIC ratio ≥ 125.

Results

A total of 189 children (492 concentrations) were included. A two-compartment model with first-order absorption and elimination best described the data. An allometric model was used to describe bodyweight (BW) influence, and effects of estimated glomerular filtration rate (eGFR) and age were significant on ciprofloxacin clearance.

Conclusion

The recommended IV dose of 10 mg/kg q8h, not exceeding 400 mg q8h, would achieve AUC0-24 h to successfully treat bacteria with MICs ≤ 0.25 (e.g. Salmonella, Escherichia coli, Proteus, Haemophilus, Enterobacter, and Klebsiella). A dose increase to 600 mg q8h in children > 40 kg and to 15 mg/kg q8h (max 400 mg q8h, max 600 mg q8h if augmented renal clearance, i.e., eGFR > 200 mL/min/1.73 m2) in children < 40 kg would be needed for the strains with highest MIC (16% of Pseudomonas aeruginosa and 47% of Staphylococcus aureus). The oral recommended dose of 20 mg/kg q12h (not exceeding 750 mg) would cover bacteria with MICs ≤ 0.125 but may be insufficient for bacteria with higher MIC and a dose increase according bodyweight and eGFR would be needed. These doses should be prospectively confirmed, and a therapeutic drug monitoring could be used to refine them individually.

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Data availability

Yes.

Code availability

Yes.

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Author information

Affiliations

Authors

Contributions

M. Oualha and JM. Treluyer conceived and designed the analysis; M. Oualha, S. Blanot, R. Rubinstazjn, C. Glorion, D. Drummond, V. Lopez, J. Toubiana, A. Béranger, Carmen Capito, S. Winter, P.L. Léger, and R. Berthaud contributed to the data; S. Boujaafar, I. Gana, Y Zheng, and S. Messaoudi contributed to analysis tool; D. Hirt, S. Benaboud, B. Pasquiers, N. Bouazza, and F. Foissac performed or contributed to the analysis; and D. Hirt wrote the paper.

Corresponding author

Correspondence to D. Hirt.

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Competing interests

The authors declare no competing interests.

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Hirt, D., Oualha, M., Pasquiers, B. et al. Population pharmacokinetics of intravenous and oral ciprofloxacin in children to optimize dosing regimens. Eur J Clin Pharmacol (2021). https://doi.org/10.1007/s00228-021-03174-1

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Keywords

  • Population pharmacokinetics
  • Ciprofloxacin
  • Children
  • Dose optimization