Pharmacology of the ACAT inhibitor avasimibe (CI-1011).

摘要: Avasimibe is a novel orally bioavailable ACAT inhibitor, currently under clinical development (phase III trials). It was safe when administered to rats, dogs, and humans. In vitro studies in human macrophages demonstrated that avasimibe reduces foam cell formation not only by enhancing free cholesterol efflux, but also inhibiting the uptake of modified LDL. The concentration-dependent reduction cellular cholesteryl ester content these cells accompanied an increase intracellular cholesterol, which agreement with good safety profile for avasimibe. liver, caused significant secretion apo B B-containing lipoproteins into plasma. induced 7alpha-hydroxylase increased bile acid synthesis cultured rat hepatocytes, its administration rats did produce lithogenicity index bile. hypolipidemic efficacy compound cholesterol-fed as well non-cholesterol-fed animals. models, plasma levels were reduced, mainly due decrease non-HDL fraction. Clinical data are scarce, study performed 130 men women combined hyperlipidemia hypoalphalipoproteinemia, avasimibe, 50-500 mg/day, significantly reduced total triglyceride VLDL-cholesterol. Although LDL-cholesterol, HDL-cholesterol unchanged, it must be stressed animal suggest may have direct antiatherosclerotic activity addition cholesterol-lowering effect. treatment can contribute plaque stability, accumulation lipids arterial wall, inhibits macrophage infiltration media matrix metalloproteinase expression activity. Moreover, statins been shown synergistic effects, combination therapy inhibit atherosclerotic lesion progression induce regression, independently changes cholesterol.