Colestipol, cholesterol-lowering effects

Colestipol was well tolerated and reduced plasma cholesterol levels during a 2 year study in types II, III and IV hyperlipoproteinemic subjects.In another study, colestipol, at a daily dose of 15 g, decreased plasma cholesterol levels in type II and IV subjects. The addition of clofibrate further reduced cholesterol values. Serum triglyceride levels were elevated by colestipol but the effect could be reversed by clofibrate.61 Similar triglyceride elevations have been observed with cholestyramlne62 which, during the past year received FDA approval for a lipid-lowering indication. 

A combination of bile acid sequestrants with nicotinic acid or probucol or an HMG-CoA reductase inhibitor can be used to produce synergistic effects in lowering plasma lipoprotein levels, particularly LDL. The efficacy of drug treatment was shown in a recent study in which lovas-tatin and colestipol were used to reduce cholesterol levels in men with CHD. The rate of progression of coronary lesions was decreased and that of regression increased. These changes also were associated with reduced cardiovascular abnormalities. 

Cholestyramine and colestipol are bile acid sequestranls that enhance cholesterol loss into the feces, thereby stimulating new bile salt synthesis, which lowers liver cholesterol levels and consequently plasma LDL levels. Their adverse effects are also listed. 

A more physicochemical mechanism for lowering serum cholesterol is by the sequestering of bile acids in the gut ionically, causing their fecal excretion rather than allowing reabsorption. The quaternary ammonium anion-exchange resin cholestyramine (Table 11-6), which is a copolymer styrene and divinylbenzene, does this effectively so does colestipol, a copolymeric resin without aromatic components. The resins, though hydrophilic, are not water soluble, are not absorbed, and are not degraded. 

Cholestyramine was originally developed in the 1960s to treat pruritus secondary to elevated plasma concentrations of bile acids in patients with cholestasis. Its ability to bihd (i.e., to hold or to sequester) bile acids and to increase their fecal eliminafion was subsequently shown to produce beneficial effects in lowering serum cholesterol levels. In 1973, cholestyramine was approved for fhe treatment of hypercholesterolemia ih patiehts who do hot respond to dietary modifications. Colestipol and colesevelam, which retain the key structural features required to bind bile acids, were approved in 1977 and 2000, respectively (7,15). 

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