Ezetimibe selectively inhibits intestinal cholesterol absorption in rodents in the presence and absence of exocrine pancreatic function.

Content Provider	Semantic Scholar
Author	Heek, Margaret Van Farley, Constance
Copyright Year	2001
Abstract	1. Ezetimibe potently inhibits the transport of cholesterol across the intestinal wall, thereby reducing plasma cholesterol in preclinical animal models of hypercholesterolemia. The effect of ezetimibe on known absorptive processes was determined in the present studies. 2. Experiments were conducted in the hamster and/or rat to determine whether ezetimibe would affect the absorption of molecules other than free cholesterol, namely cholesteryl ester, triglyceride, ethinylestradiol, progesterone, vitamins A and D, and taurocholic acid. In addition, to determine whether exocrine pancreatic function is involved in the mechanism of action of ezetimibe, a biliary anastomosis model, which eliminates exocrine pancreatic function from the intestine while maintaining bile flow, was established in the rat. 3. Ezetimibe reduced plasma cholesterol and hepatic cholesterol accumulation in cholesterol-fed hamsters with an ED(50) of 0.04 mg kg(-1). Utilizing cholesteryl esters labelled on either the cholesterol or the fatty acid moiety, we demonstrated that ezetimibe did not affect cholesteryl ester hydrolysis and the absorption of fatty acid thus generated in both hamsters and rats. The free cholesterol from this hydrolysis, however, was not absorbed (92 - 96% inhibition) in the presence of ezetimibe. Eliminating pancreatic function in rats abolished hydrolysis of cholesteryl esters, but did not affect the ability of ezetimibe to block absorption of free cholesterol (-94%). Ezetimibe did not affect the absorption of triglyceride, ethinylestradiol, progesterone, vitamins A and D, and taurocholic acid in rats. 4. Ezetimibe is a potent inhibitor of intestinal free cholesterol absorption that does not require exocrine pancreatic function for activity. Ezetimibe does not affect the absorption of triglyceride as a pancreatic lipase inhibitor (Orlistat) would, nor does it affect the absorption of vitamin A, D or taurocholate, as a bile acid sequestrant (cholestyramine) would.
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://pubmedcentralcanada.ca/pmcc/articles/PMC1572957/pdf/134-0704260a.pdf
PubMed reference number	11564660v1
Volume Number	134
Issue Number	2
Journal	British journal of pharmacology
Language	English
Access Restriction	Open
Subject Keyword	Animal Model Bile Acids Bile acid sequestrants Bile fluid Cholesterol Esters Cholestyramine Resin Ethinyl Estradiol Fatty Acids Hamsters Hypercholesterolemia Intestinal Wall Tissue Intestines Lipase Progesterone Rodent Structure of beta Cell of islet Taurocholate Taurocholic Acid Triglycerides Vitamin A ezetimibe intestinal cholesterol absorption orlistat
Content Type	Text
Resource Type	Article