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Comparison of the Influence of Cyclosporine and Tacrolimus on the Pharmacokinetics of Prednisolone in Adult Male Kidney Transplant Recipients

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Abstract

Background and Objective

Cyclosporine has been observed to precipitate cushingoid features in kidney transplant recipients already on prednisolone. Some pharmacokinetic studies have demonstrated increased prednisolone exposure in patients on cyclosporine therapy compared with azathioprine, whereas other studies have found no difference. The objective of this study was to determine whether cyclosporine impacts on prednisolone exposure as compared with tacrolimus.

Methods

Adult male kidney transplant recipients treated with prednisolone and either cyclosporine or tacrolimus were recruited for pharmacokinetic blood sampling at the outpatient clinic at the Princess Alexandra Hospital, Brisbane, Australia. Prednisolone plasma concentrations were determined using ultra-high-performance liquid chromatography. Dose-adjusted area under the plasma concentration–time curve (AUC) of free and total prednisolone was estimated using a previously developed limited sampling strategy and non-compartmental analysis.

Results

A total of 55 patients were eligible for analysis; 38 % received cyclosporine and 62 % received tacrolimus co-therapy. No significant difference in mean dose-adjusted total prednisolone AUC from 0 to 6 h post-dose or mean dose-adjusted free prednisolone AUC from 0 to 12 h was observed between the cyclosporine and tacrolimus groups (449 versus 428 nmol·h/L/mg, p = 0.43, and 32 versus 30 nmol·h/L/mg, p = 0.51, respectively).

Conclusion

Cyclosporine does not change the dose-adjusted exposure of prednisolone compared with tacrolimus. Adult kidney transplant recipients can therefore continue on their usual prednisolone dose when changing therapy between cyclosporine and tacrolimus.

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Acknowledgments

The authors acknowledge financial support from a National Health and Medical Research Council (NHMRC) Project Grant #511109. No author has any conflict of interest to declare.

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Authors and Affiliations

  1. School of Pharmacy, University of Queensland, Brisbane, Australia

    Troels K. Bergmann & Christine E. Staatz

  2. Department of Clinical Pharmacology, Aarhus University Hospital, Wilhelm Meyers Alle 4, 8000, Aarhus C, Denmark

    Troels K. Bergmann

  3. Department of Nephrology, University of Queensland at the Princess Alexandra Hospital, Brisbane, Australia

    Nicole M. Isbel, Katherine A. Barraclough & Scott B. Campbell

  4. Department of Chemical Pathology, Pathology Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Australia

    Brett C. McWhinney

Authors
  1. Troels K. Bergmann
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  2. Nicole M. Isbel
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  3. Katherine A. Barraclough
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  4. Scott B. Campbell
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  5. Brett C. McWhinney
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  6. Christine E. Staatz
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Correspondence to Troels K. Bergmann.

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Bergmann, T.K., Isbel, N.M., Barraclough, K.A. et al. Comparison of the Influence of Cyclosporine and Tacrolimus on the Pharmacokinetics of Prednisolone in Adult Male Kidney Transplant Recipients. Clin Drug Investig 34, 183–188 (2014). https://doi.org/10.1007/s40261-013-0162-1

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