Comparison of the influence of cyclosporine and tacrolimus on the pharmacokinetics of prednisolone in adult male kidney transplant recipients

Bergmann, Troels K., Isbel, Nicole M., Barraclough, Katherine A., Campbell, Scott B., McWhinney, Brett C. and Staatz, Christine E. (2014) Comparison of the influence of cyclosporine and tacrolimus on the pharmacokinetics of prednisolone in adult male kidney transplant recipients. Clinical Drug Investigation, 34 3: 183-188. doi:10.1007/s40261-013-0162-1

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Author Bergmann, Troels K.
Isbel, Nicole M.
Barraclough, Katherine A.
Campbell, Scott B.
McWhinney, Brett C.
Staatz, Christine E.
Title Comparison of the influence of cyclosporine and tacrolimus on the pharmacokinetics of prednisolone in adult male kidney transplant recipients
Journal name Clinical Drug Investigation   Check publisher's open access policy
ISSN 1173-2563
1179-1918
Publication date 2014-03-01
Year available 2014
Sub-type Article (original research)
DOI 10.1007/s40261-013-0162-1
Open Access Status File (Author Post-print)
Volume 34
Issue 3
Start page 183
End page 188
Total pages 6
Place of publication Mairangi Bay, Auckland, New Zealand
Publisher Adis International
Language eng
Formatted 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.
Keyword Pharmacology & Pharmacy
Pharmacology & Pharmacy
PHARMACOLOGY & PHARMACY
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 511109
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
School of Pharmacy Publications
 
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Created: Tue, 18 Feb 2014, 02:20:50 EST by Dr Christine Staatz on behalf of School of Pharmacy