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Influence of Everolimus on Steady‐State Pharmacokinetics of Cyclosporine in Maintenance Renal Transplant Patients
Author(s) -
Budde Klemens,
Lehne Gustav,
Winkler Michael,
Renders Lutz,
Lison Arno,
Fritsche Lutz,
Soulillou JeanPaul,
Fauchald Per,
Neumayer HansHellmut,
Dantal Jaques
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005277196
Subject(s) - everolimus , pharmacokinetics , medicine , renal transplant , pharmacology , urology , intensive care medicine , transplantation
To investigate possible interactions of the novel immunosuppressant everolimus with cyclosporine, a multicenter, randomized, double‐blind, placebo‐controlled, dose‐escalating phase I study was performed. Everolimus regimens (0.75–10 mg/d) were administered for 28 days to stable renal allograft recipients receiving the microemulsion form of cyclosporine. Steady‐state cyclosporine profiles were assessed at baseline on day 0 (cyclosporine alone) and on day 21 with everolimus on steady state. By day 21, mean dose‐normalized cyclosporine AUC 0–12 increased by 15% in patients receiving placebo. In everolimus‐treated patients, mean increases in cyclosporine AUC 0–12 ranged from 7% to 43%, which were not significantly different across all dosing cohorts including placebo. Linear regression of everolimus AUC on day 21 versus the increase in cyclosporine AUC 0–12 yielded a slope not significantly different from a horizontal line (P = ns). In conclusion, these results suggest that steady‐state everolimus exposure over the wide range assessed in this study did not affect steady‐state cyclosporine pharmacokinetics.