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.
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.
Authors: M Vogt; H Derendorf; J Krämer; H E Junginger; K K Midha; V P Shah; S Stavchansky; J B Dressman; D M Barends Journal: J Pharm Sci Date: 2007-01 Impact factor: 3.534
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