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.
Bergman
Arthur J
AJ
Clinical Drug Metabolism, Merck Research Laboratories, WP 75-100, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.
Burke
Joanne
J
Larson
Patrick
P
Johnson-Levonas
Amy O
AO
Reyderman
Larisa
L
Statkevich
Paul
P
Maxwell
Stephen E
SE
Kosoglou
Teddy
T
Murphy
Gail
G
Gottesdiener
Keith
K
Robson
Richard
R
Paolini
John F
JF
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