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Effects of Calcineurin Inhibitors on Sirolimus Pharmacokinetics During Staggered Administration in Renal Transplant Recipients

Effects of Calcineurin Inhibitors on Sirolimus Pharmacokinetics During Staggered Administration in Renal Transplant Recipients

Fe-Lin Lin Wu, Meng-Kun Tsai, Russel Rhei-Long Chen, Shao-Wen Sun, Jin-Ding Huang, Rey-Heng Hu, Kuo-Hsin Chen, Po-Huang Lee

Pharmacotherapy. 2005 May;25(5):646-53.

PMID: 15899725

Abstract:

Study objective:
To compare the effects of different calcineurin inhibitors on sirolimus pharmacokinetics during long-term, staggered administration in kidney transplant recipients. Design. Randomized, open-label, parallel-group trial.
Setting:
A medical center and one of its teaching hospitals in Taiwan.
Patients:
Twenty-two de novo kidney transplant recipients.
Intervention:
Patients received cyclosporine microemulsion or tacrolimus capsules twice/day in combination with once-daily sirolimus solution and corticosteroids. Sirolimus was administered 6 hours after the morning dose of cyclosporine or tacrolimus. After receiving a 6-mg loading dose of sirolimus, participants received sirolimus 2 mg/day for at least 7 days. Neither the cyclosporine nor the tacrolimus dosage was adjusted for at least 3 days before and during blood sampling for pharmacokinetic profiling.
Measurements and main results:
One patient dropped out because of trimethoprim-sulfamethoxazole-related hepatotoxicity. We observed no differences between the two patient groups in terms of their demographic data, renal and liver function, or dosage of sirolimus during the study. During multiple-dose administration, the area under the whole-blood concentration-time curve and the peak and trough concentrations of sirolimus in the cyclosporine group were, respectively, 1.46 (95% confidence interval [CI] 1.21-1.71), 1.42 (95% CI 1.08-1.76), and 1.42 (95% CI 1.09-1.76) times higher than those of the tacrolimus group, even though sirolimus was administered 6 hours after the other agents.
Conclusion:
Sirolimus pharmacokinetics may change significantly when calcineurin inhibitors are switched, even with staggered administration, which may not completely prevent a drug interaction between cyclosporine and sirolimus solution.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP53123889-B	Sirolimus solution		53123-88-9	Price

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