Effects of ezetimibe on cyclosporine pharmacokinetics in healthy subjects.
This single-center, open-label, 2-period crossover study investigated the effects of multiple-dose ezetimibe (EZE) on a single dose of cyclosporine (CyA). Healthy subjects received 2 treatments in random order with a 14-day washout: (1) CyA 100 mg alone and (2) EZE 20 mg for 7 days with CyA 100 mg coadministered on day 7; EZE 20 mg alone was administered on day 8. AUC(0-last) and Cmax geometric mean ratios (90% confidence interval) for ([CyA + EZE]/CyA alone) were 1.15 (1.07, 1.25) and 1.10 (0.97, 1.26), respectively. Tmax (approximately 1.3 hours) was similar with and without EZE (P >.200). Mean CyA exposure slightly increased (approximately 15%) with multiple-dose EZE 20 mg; however, this value was contained within (0.80, 1.25). The implications for chronic EZE dosing within the usual clinical paradigm of chronic CyA dosing have not been established; caution is recommended when using these agents concomitantly. CyA concentrations should be monitored in patients receiving EZE and CyA.
Bergman
Arthur J
AJ
Merck Research Laboratories, West Point, PA 19486, USA.
Burke
Joanne
J
Larson
Patrick
P
Johnson-Levonas
Amy O
AO
Reyderman
Larisa
L
Statkevich
Paul
P
Kosoglou
Teddy
T
Greenberg
Howard E
HE
Kraft
Walter K
WK
Frick
Glenn
G
Murphy
Gail
G
Gottesdiener
Keith
K
Paolini
John F
JF
D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D019540:Area Under Curve; D001384:Azetidines / Q000494:pharmacology*; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D008297:Male
D000924:Anticholesteremic Agents; D001384:Azetidines; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000069438:Ezetimibe