Interaction of single-dose ezetimibe and steady-state cyclosporine in renal transplant patients.
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 Cmax 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 Cmax 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.
Clinical Drug Metabolism, Merck Research Laboratories, WP 75-100, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.
Arthur J
AJ
Bergman
Joanne
J
Burke
Patrick
P
Larson
Amy O
AO
Johnson-Levonas
Larisa
L
Reyderman
Paul
P
Statkevich
Stephen E
SE
Maxwell
Teddy
T
Kosoglou
Gail
G
Murphy
Keith
K
Gottesdiener
Richard
R
Robson
John F
JF
Paolini
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001384:Azetidines / Q000097:blood / Q000493:pharmacokinetics*; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged
D000924:Anticholesteremic Agents; D001384:Azetidines; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000069438:Ezetimibe