Sudhop T, Reber M, Tribble D, Sapre A, Taggart W, Gibbons P, Musliner T, von Bergmann K, Lütjohann D.

Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men

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, 4-period crossover study to evaluate the effects of coadministering ezetimibe 10 mg with simvastatin 20 mg (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-C 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-C for the coadministration of ezetimibe and simvastatin.