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

  • Pharmacokinetics and Disposition
  • Published:
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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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Author information

Authors and Affiliations

  1. EA7323, Evaluation des Thérapeutiques et Pharmacologie Périnatale et Pédiatrique, Université de Paris, 89 rue d’Assas, 75014, Paris, France

    D. Hirt, M. Oualha, B. Pasquiers, S. El Messaoudi, A. Béranger, Sana Boujaafar, Yi Zheng, Inès Gana, F. Foissac, J. M. Tréluyer, N. Bouazza & S. Benaboud

  2. Service de Pharmacologie Clinique, AP-HP, Hôpital Cochin, 27 rue du Faubourg Saint Jacques, 75014, Paris, France

    D. Hirt, Sana Boujaafar, Yi Zheng, Inès Gana, J. M. Tréluyer & S. Benaboud

  3. INSERM, U1018, Hôpital de Bicêtre, 78 Rue du Général Leclerc, 94270, Le Kremlin-Bicêtre, France

    D. Hirt

  4. Service de Réanimation et Surveillance Continue Médico-Chirurgicales Pédiatriques, Hôpital Necker Enfants Malades, 149 Rue de Sèvres, 75015, Paris, France

    M. Oualha & A. Béranger

  5. Service de Neurochirurgie, Hôpital Necker Enfants Malades, 149 Rue de Sèvres, 75015, Paris, France

    S. Blanot

  6. Service de Réanimation Chirurgicale Pédiatrique, Hôpital Necker Enfants Malades, 149 Rue de Sèvres, 75015, Paris, France

    R. Rubinstazjn

  7. Service de Chirurgie Orthopédique et Traumatologie Pédiatrique, Hôpital Necker Enfants Malades, 149 Rue de Sèvres, 75015, Paris, France

    C. Glorion

  8. Service de Pneumologie Pédiatrique, Hôpital Necker Enfants Malades, 149 Rue de Sèvres, 75015, Paris, France

    D. Drummond

  9. Service de Réanimation Cardiaque Pédiatrique, Hôpital Necker Enfants Malades, 149 Rue de Sèvres, 75015, Paris, France

    V. Lopez

  10. Service de Pédiatrie Générale - Équipe Mobile D’infectiologie, Hôpital Necker Enfants Malades, AP-HP, Université de Paris, 149 Rue de Sèvres, 75015, Paris, France

    J. Toubiana

  11. Service de Chirurgie Viscérale et Urologique Pédiatriques, Hôpital Necker Enfants Malades, 149 Rue de Sèvres, 75015, Paris, France

    Carmen Capito

  12. Service d’hématologie, Immunologie et Rhumatologie Pédiatrique Hôpital Necker Enfants Malades, 149 Rue de Sèvres, 75015, Paris, France

    S. Winter

  13. Service de Réanimation Pédiatrique, Hôpital Armand Trousseau, 26 Avenue du Dr Arnold Netter, 75012, Paris, France

    P. L. Léger

  14. Service de Néphrologie Pédiatrique, Hôpital Necker Enfants Malades, 149 Rue de Sèvres, 75015, Paris, France

    R. Berthaud

  15. Unite de Recherche Clinique Paris Descartes Necker Cochin, AP-HP, 89 rue d’Assas, 75014, Paris, France

    R. Berthaud, F. Foissac, J. M. Tréluyer & N. Bouazza

  16. CIC-1419 Inserm, Cochin-Necker, 149 Rue de Sèvres, 75015, Paris, France

    R. Berthaud, F. Foissac, J. M. Tréluyer & N. Bouazza

Authors
  1. D. Hirt
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  2. M. Oualha
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  3. B. Pasquiers
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  4. S. Blanot
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  5. R. Rubinstazjn
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  6. C. Glorion
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  7. S. El Messaoudi
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  8. D. Drummond
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  9. V. Lopez
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  10. J. Toubiana
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  11. A. Béranger
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  12. Sana Boujaafar
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  13. Yi Zheng
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  14. Carmen Capito
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  15. S. Winter
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  16. P. L. Léger
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  17. R. Berthaud
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  18. Inès Gana
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  19. F. Foissac
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  20. J. M. Tréluyer
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  21. N. Bouazza
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  22. S. Benaboud
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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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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 77, 1687–1695 (2021). https://doi.org/10.1007/s00228-021-03174-1

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  • DOI: https://doi.org/10.1007/s00228-021-03174-1

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