title: Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men.
abstract: This study evaluates changes in cholesterol balance in hypercholesterolemic subjects following treatment with an inhibitor of cholesterol absorption or cholesterol synthesis or coadministration of both agents. This was a randomized, double blind, placebo-controlled, four-period crossover study to evaluate the effects of coadministering 10 mg ezetimibe with 20 mg simvastatin (ezetimibe/simvastatin) on cholesterol absorption and synthesis relative to either drug alone or placebo in 41 subjects. Each treatment period lasted 7 weeks. Ezetimibe and ezetimibe/simvastatin decreased fractional cholesterol absorption by 65% and 59%, respectively (P < 0.001 for both relative to placebo). Simvastatin did not significantly affect cholesterol absorption. Ezetimibe and ezetimibe/simvastatin increased fecal sterol excretion (corrected for dietary cholesterol), which also represents net steady state cholesterol synthesis, by 109% and 79%, respectively (P < 0.001). Ezetimibe, simvastatin, and ezetimibe/simvastatin decreased plasma LDL-cholesterol by 20, 38, and 55%, respectively. The coadministered therapy was well tolerated. The decreases in net cholesterol synthesis and increased fecal sterol excretion yielded nearly additive reductions in LDL-cholesterol for the coadministration of ezetimibe and simvastatin.
authors.affiliation: Institute of Clinical Chemistry and Pharmacology, University of Bonn, Bonn, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sudhop
authors.forename: Michael
authors.initials: M
authors.lastname: Reber
authors.forename: Diane
authors.initials: D
authors.lastname: Tribble
authors.forename: Aditi
authors.initials: A
authors.lastname: Sapre
authors.forename: William
authors.initials: W
authors.lastname: Taggart
authors.forename: Patrice
authors.initials: P
authors.lastname: Gibbons
authors.forename: Thomas
authors.initials: T
authors.lastname: Musliner
authors.forename: Klaus
authors.initials: K
authors.lastname: von Bergmann
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001384:Azetidines / Q000627:therapeutic use*; D002784:Cholesterol / Q000378:metabolism*; D004311:Double-Blind Method; D004338:Drug Combinations; D000069438:Ezetimibe; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D004338:Drug Combinations; D002784:Cholesterol; D019821:Simvastatin; D000069438:Ezetimibe