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Moxifloxacin does not Alter Ciclosporin Pharmacokinetics in Transplant Patients

A Multiple-Dose, Uncontrolled, Single-Centre Study

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Abstract

Background: Moxifloxacin has a broad antibacterial spectrum and rapid bactericidal activity, and is thus a good option for the treatment of bacterial infections in patients who have undergone organ or bone marrow transplantation. Transplant patients also receive immunosuppressant therapy such as ciclosporin.

Objectives: The primary objective of this study was to assess the steady-state pharmacokinetics of ciclosporin with and without concomitant treatment with moxifloxacin in transplant recipients. A secondary objective was to determine the safety and tolerability of the combined treatment.

Methods: Patients (n = 9) with stable graft function after bone marrow or renal transplantation and who were already receiving ciclosporin therapy were enrolled into the study. The patients were given ciclosporin (Sandimmun® Optoral) capsules twice daily (total daily dosage 150–380 mg/day) throughout the study period. Moxifloxacin (Avolox®) tablets 400 mg once daily were given on days 2–8 inclusive. The primary outcome measure was the change in ciclosporin pharmacokinetics on coadministration with moxifloxacin. Secondary outcomes were the steady-state pharmacokinetics of moxifloxacin and ciclosporin plus its metabolites in patients receiving moxifloxacin and ciclosporin concomitantly. Moxifloxacin pharmacokinetic parameters in the presence of ciclosporin were compared with previously published pharmacokinetic data for moxifloxacin in healthy individuals.

Results: No significant changes occurred in the concentration-time curves of ciclosporin and its metabolites following combination therapy with moxifloxacin. The geometric means of whole blood concentrations of ciclosporin and ciclosporin plus its metabolites on day 1 were similar to those on day 8 following combined administration of ciclosporin and moxifloxacin for 7 days. The ratio of combination treatment to monotherapy for ciclosporin was 1.01 (90% CI 0.91, 1.11) for the area under the blood concentration-time curve from time zero to 12 hours at steady state (AUC12ss) and 0.96 (90% CI 0.88, 1.04) for the maximum steady-state blood drug concentration (Cmax,ss). For ciclosporin plus its metabolites the ratio was 1.07 (90% CI 0.99, 1.17) for AUC12,ss and 1.03 (90% CI 0.98, 1.09) for Cmax,ss. The pharmacokinetic parameters for moxifloxacin were unaffected by the presence of ciclosporin.

Conclusions: Concomitant administration of moxifloxacin does not alter the pharmacokinetic parameters of ciclosporin or ciclosporin plus its metabolites in immunosuppressed patients. Therefore, no dose adjustments or additional drug monitoring are required when ciclosporin is coadministered with moxifloxacin.

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Acknowledgements

This study was funded by Bayer HealthCare AG, Wuppertal, Germany. Highfield Communication Consultancy (funded by Bayer HealthCare AG) and Bayer HealthCare AG provided editorial assistance in the preparation of this manuscript. The authors thank Claudia Maschke for co-ordinating the study. H. Stass, H. Delesen and D. Kubitza are employees of Bayer HealthCare AG. The other authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Bayer Healthcare AG, Clinical Pharmacology, Room 219, Building 470, D-42096, Wuppertal, Germany

    Heino Stass (PhD) & Dagmar Kubitza

  2. Bayer HealthCare AG, Elberfeld, Germany

    Heinz Delesen

  3. Institute of Clinical Pharmacology and Toxicology, Charité Universitätsmedizin Berlin, Berlin, Germany

    Ingrid Mai, Steffen Bauer & Ivar Roots

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  1. Heino Stass
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  2. Heinz Delesen
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  3. Dagmar Kubitza
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Correspondence to Heino Stass.

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Stass, H., Delesen, H., Kubitza, D. et al. Moxifloxacin does not Alter Ciclosporin Pharmacokinetics in Transplant Patients. Clin. Drug Investig. 30, 279–287 (2010). https://doi.org/10.1007/BF03256904

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