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Interaction of Single‐Dose Ezetimibe and Steady‐State Cyclosporine in Renal Transplant Patients
Author(s) -
Bergman Arthur J.,
Burke Joanne,
Larson Patrick,
JohnsonLevonas Amy O.,
Reyderman Larisa,
Statkevich Paul,
Maxwell Stephen E.,
Kosoglou Teddy,
Murphy Gail,
Gottesdiener Keith,
Robson Richard,
Paolini John F.
Publication year - 2006
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 - 10.1177/0091270005284852
Subject(s) - medicine , pharmacokinetics , dosing , renal transplant , pharmacology , ezetimibe , toxicity , morning , urology , gastroenterology , kidney , statin
This open‐label, single‐period study evaluated the single‐dose pharmacokinetics of ezetimibe (EZE) 10 mg in the setting of steady‐state cyclosporine (CyA) dosing in renal transplant patients. A single 10‐mg dose of EZE was coadministered with the morning dose of CyA (75–150 mg twice a day). Total EZE (sum of unconjugated, parent EZE and EZE‐glucuronide; EZE‐total) AUC 0‐last and C max were compared to values derived from a prespecified database of healthy volunteers. Geometric mean ratios (90% CIs) for (EZE + CyA)/EZE alone for EZE‐total AUC (0‐last) and C max were 3.41 (2.55, 4.56) and 3.91 (3.13, 4.89), respectively. Compared to healthy controls, EZE‐total AUC (0‐last) was 3.4‐fold higher in transplant patients receiving CyA; similar exposure levels were seen in a prior multiple‐dose study in which EZE 50 mg was administered to healthy volunteers without dose‐related toxicity. Because the long‐term safety implications of both higher EZE exposures and undetermined effect on CyA are not yet understood, the clinical significance of this interaction is unknown.