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Effect of ciprofloxacin on the pharmacokinetics of ropivacaine

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

To assess the effect of ciprofloxacin on the pharmacokinetics of ropivacaine.

Methods

In a double-blind, randomised, cross-over study, nine healthy volunteers were treated for 2.5 days with 500 mg oral ciprofloxacin or placebo twice daily. On day 3, they received a single dose of 0.6 mg/kg ropivacaine intravenously over 30 min. Ropivacaine, 3-hydroxyropivacaine (3-OH-ropivacaine), and (S)-2′,6′-pipecoloxylidide (PPX) in venous plasma and urine were measured for up to 12 h and 24 h, respectively.

Results

Ciprofloxacin decreased the mean clearance (CL) of ropivacaine by 31% (P<0.05), with a considerable inter-individual variation (range from −52% to +39%). It also decreased the area under the plasma concentration–time curve (AUC) of 3-OH-ropivacaine by 38% (P<0.05) and urinary excretion of 3-OH-ropivacaine by 27% (P<0.05). Ciprofloxacin increased the AUC of PPX by 71% (P<0.01) and urinary excretion of PPX by 97% (P<0.01).

Conclusion

Ciprofloxacin modestly decreased the mean ropivacaine CL by inhibiting the CYP1A2-mediated formation of 3-OH-ropivacaine. At the same time, the CYP3A4-mediated formation of PPX was increased. There was a marked inter-individual variation in the extent of the interaction, and, for some individuals, the concomitant use of ciprofloxacin with ropivacaine might produce toxic symptoms.

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Acknowledgements

We thank Jouko Laitila, Kerttu Mårtensson, Mikko Neuvonen and Lisbet Partanen for the skilful determination of plasma and urine drug concentrations; and Pirkko Herranen, Anne Karhu, Minna Korvenpää and Anja Liukko for excellent technical assistance. This study was supported by grants from the Helsinki University Central Hospital Research Fund and the National Technology Agency of Finland (TEKES), and it complies with the current laws of Finland.

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Authors and Affiliations

  1. Department of Anaesthesia and Intensive Care, Helsinki University Central Hospital, P.O. Box 340, 00029 HUS, Finland

    Mika J. Jokinen, Klaus T. Olkkola & Jouni Ahonen

  2. Department of Clinical Pharmacology, University of Helsinki, P.O. Box 20, 00029 HUS, Finland

    Mika J. Jokinen & Pertti J. Neuvonen

Authors
  1. Mika J. Jokinen
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  2. Klaus T. Olkkola
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  3. Jouni Ahonen
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  4. Pertti J. Neuvonen
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Correspondence to Mika J. Jokinen.

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Jokinen, M.J., Olkkola, K.T., Ahonen, J. et al. Effect of ciprofloxacin on the pharmacokinetics of ropivacaine. Eur J Clin Pharmacol 58, 653–657 (2003). https://doi.org/10.1007/s00228-002-0540-8

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  • DOI: https://doi.org/10.1007/s00228-002-0540-8

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