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Atorvastatin does not affect the pharmacokinetics of cyclosporine in renal transplant recipients

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Abstract

Objective

The aim of the present study was to evaluate the possible influence of atorvastatin on the pharmacokinetics of cyclosporine (INN ciclosporin) and its main metabolites, AM1 and AM9, in renal transplant recipients.

Methods

Whole blood samples from 18 renal transplanted patients on cyclosporine-based immunosuppressive therapy were collected prior to and after 4 weeks of treatment with atorvastatin (10 mg/day) and analysed with regard to both cyclosporine and its main metabolites, AM1 and AM9, using a specific chromatographic method with ultraviolet detection.

Results

On average, AUC0-12 [area under the whole blood concentration versus time curve in the dosing interval (0–12 h)] of cyclosporine was 5% (−16, 5) (90% confidence interval) lower upon co-administration with atorvastatin. No statistically significant changes in any of the calculated pharmacokinetic variables [AUC0-12, maximum whole blood concentration (Cmax), whole blood concentration 12 h post dose (C12), time to Cmax (tmax), terminal half-life (t1/2)] for cyclosporine or the two metabolites, AM1 and AM9, upon atorvastatin treatment were observed. On average, atorvastatin did not affect the ratio between the CYP3A4-mediated metabolite AM9 and cyclosporine, suggesting that atorvastatin does not affect the CYP3A4 metabolism of cyclosporine to any significant extent. However, the influence of atorvastatin on the ratio between AM9 and cyclosporine showed large interindividual variability.

Conclusion

The results of this study indicate that atorvastatin does not, on average, affect cyclosporine pharmacokinetics in renal transplant recipients.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, University of Oslo, PB 1068, Blindern, N-0316, Oslo, Norway

    Monica Hermann, Anders Åsberg & Hege Christensen

  2. Department of Pharmaceutical Analysis, School of Pharmacy, University of Oslo, Norway

    Jan Leo Egge Reubsaet

  3. Laboratory for Renal Physiology, Medical Department, The National Hospital, Oslo, Norway

    Anders Åsberg, Hallvard Holdaas & Anders Hartmann

Authors
  1. Monica Hermann
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  2. Anders Åsberg
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  3. Hege Christensen
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  4. Jan Leo Egge Reubsaet
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  5. Hallvard Holdaas
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  6. Anders Hartmann
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Corresponding author

Correspondence to Monica Hermann.

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Hermann, M., Åsberg, A., Christensen, H. et al. Atorvastatin does not affect the pharmacokinetics of cyclosporine in renal transplant recipients. Eur J Clin Pharmacol 61, 59–62 (2005). https://doi.org/10.1007/s00228-004-0874-5

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  • DOI: https://doi.org/10.1007/s00228-004-0874-5

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