Colestipol metabolism

Interactions Antacids ciclosporin colestipol druas metabolized bv cytochrome P450 3A4 fibrates oral-contraceptiyes warfarin niacin erythromycin diaoxin azole-antifunaals... 

In addition to treatment with the statins, hypercholesterolemia is sometimes treated with the use of nonabsorbable anion-exchange resins like cholestyramine (5.13) and colestipol, which sequester bile acid in the intestine, excrete them, and thus increase their synthesis in the liver by a feedback mechanism. Increased bile acid synthesis increases cholesterol metabolism and also decreases LDL concentrations. Unfortunately, these resins interfere with the absorption of other fats and fat-soluble vitamins (A, D, E, and K). They... 

Bile acid sequestrates are anion-exchange resins, which sequester bile acid in the intestine. Cholestyramine and colestipol are the most commonly used in this category, which by this mechanism prevents bile acid re-absorption and causes decreased absorption of exogenous cholesterol and increased metabolism of endogenous cholesterol into bile acid in the liver by preventing enterohepatic recirculation. This leads to an increased expression of LDL receptors in liver and causes increased removal of LDL from blood and reduces the LDL cholesterol in the plasma. 

Pharmacokinetics Cholestyramine and colestipol are taken orally. Because they are insoluble in water and are very large (molecular weights are greater than 106), they are neither absorbed nor metabolically altered by the intestine. Instead, they are totally excreted in the feces. 

A large scale trial with patients treated for up to 3 years with colestipol showed lower cardiovascular mortality in men, but not in women."" The resins lower LDL-C a study with colestipol showed no change in HDL-C." The metabolic disposition of oral [ C]colestipol was studied in rats, dogs and man absorption was negligible and virtually all of the radioactivity was excreted in feces. ... 

Barbiturates, phenytoin, and rifampin may cause decreased paramethasone effects because of increased hepatic metabolism. Cholestyramine, colestipol, and antacids decrease the corticosteroid effect by absorbing the corticosteroid, decreasing the amount absorbed. 

Aluminum salts, cholestyramine, and colestipol may decrease absorption of /3 blockers. Pheny-toin, rifampin, and phenobarbital, as well as smoking, induce hepatic biotransformation enzymes and may decrease plasma concentrations of /3 receptor antagonists that are metabolized extensively (e.g., propranolol). Cimetidine and hydralazine may increase bioavailability of propranolol and metoprolol by affecting hepatic blood flow, fi Receptor antagonists can impair the clearance o/lidocaine. 

Cholestyramine, colestipol, and colesevelam are not orally absorbed and are not metabolized by gastrointestinal enzymes. They are excreted in the feces as an insoluble complex with bile acids. Their onset of action occurs within 24 to 48 hours however, it may take up to 1 month to achieve peak response (7,15,20). 

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