Disease relevance of UN2320

• Treatment of primary moderate hypercholesterolemia with lovastatin (mevinolin) and colestipol [1].
• In the chronic bile fistula rat, colestipol increased bile salt synthesis by 100% while diosgenin and fructose diets had no effect [2].
• Although LDL apheresis combined with simvastatin was more effective than colestipol plus simvastatin in reducing LDL cholesterol and lipoprotein(a), it was less beneficial in influencing coronary atherosclerosis and should be reserved for patients unresponsive to drugs [3].
• Long-term colestipol therapy in conjunction with diet may reduce xanthoma size, arrest progression of coronary artery atherosclerosis, and may reduce mortality from coronary heart disease [4].
• Side effects were equally distributed between colestipol HCl and placebo and were primarily gastrointestinal (upper abdominal distress, constipation) [5].

Psychiatry related information on UN2320

• Lipid-lowering therapy may consist of dietary modification and drug treatment with colestipol hydrochloride (Colestid), cholestyramine (Cholybar, Questran), lovastatin (Mevacor), gemfibrozil (Lopid), and nicotinic acid (Nicolar) [6].

High impact information on UN2320

• We performed an analysis of the cost-effectiveness of treating individuals with significantly elevated levels of total serum cholesterol (greater than 6.85 mmol/L [greater than 265 mg/dL], comparing treatment with three alternative agents: cholestyramine resin, colestipol, and oat bran (a soluble fiber) [7].
• Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholeserolemia heterozygotes. 1983 [8].
• Interruption of the enterohepatic circulation with colestid resulted in upregulation of these parameters for both enzymes, as a consequence of stimulated gene expression mainly in the periportal zone [9].
• Thriteen patients with heterozygous familial hypercholesterolaemia (FH) were sequentially treated with: a low-cholesterol, fat-restricted diet; diet and colestipol; and diet and colestipol and nicotinic acid [10].
• HDL cholesterol levels were similar on both the diet (40 mg/dl) and colestipol (43 mg/dl) treatment periods but increased to 53 mg/dl on the combined drug regimen [10].

Chemical compound and disease context of UN2320

• Probucol with colestipol in the treatment of hypercholesterolemia [11].
• Effect of lovastatin or niacin combined with colestipol and regression of coronary atherosclerosis [12].
• The effects of colestipol HCl resin and clofibrate on plasma lipid and lipoprotein levels were compared in 65 patients with primary hypercholesterolemia [13].
• Modification of the carcinogenic process in colorectal cancer by endogenous and exogenous factors: effect of colestipol hydrochloride on tumors induced by dimethylhydrazine [14].
• The nonabsorbable bile acid sequestrant resin, colestipol, was administered to 16 patients with primary hypercholesterolemia, and its effect on serum lipids, lipoprotein fractions, and circulating platelet aggregate ratio and platelet aggregation in response to adenosine diphosphate (ADP) was compared with that of sitosterol [15].

Biological context of UN2320

• Results related to long term treatment with Colestipol (a new resin sequestering bile acids) in 23 subjects with familial hypercholesterolaemia, 12 with Type IIA, 8 with Type IIB and 3 homozygotes are reported [16].
• (4) Colestipol therapy plus diet had no effect on prothrombin time, serum 25-hydroxycholecalciferol, folate, or calcium metabolism (as studied by sequential determination of serum total and ionized calcium phosphorus, alkaline phosphatase, and parathyroid hormone) [17].
• The bioavailability was reduced by colestipol 80%, by cholestyramine 95% and by activated charcoal 99.5% [18].
• The circulating platelet aggregate ratio was significantly lower in the group of patients with hypercholesterolemia who received colestipol initially than in control subjects, but platelet aggregation in response to ADP was not significantly different between these two groups [15].
• The newest BAS, colesevelam, has greater specificity for bile acids compared with the older agents cholestyramine and colestipol, eliminating most drug interactions and reducing the tendency for constipation [19].

Anatomical context of UN2320

• In liver microsomes isolated from rats fed both mevinolin and colestipol, the Mr 100,000 form was the predominant species, whereas in microsomes from animals fed only colestipol, the Mr 200,000 species was the major form [20].
• We conclude that no major alterations in thyroid function occurred with colestipol therapy [21].
• The effect of the bile acid sequestrant, colestipol hydrochloride, on the incidence of dimethylhydrazine-induced tumors of the large intestine was determined in male Swiss mice [14].
• The taurine-conjugated and dihydroxy bile acids dissociated more slowly from cholestyramine and colestipol than the glycine-conjugated and trihydroxy bile acids and, therefore, would be expected to avoid reabsorption to a greater extent by the terminal ileum and colon in vivo [22].
• These results indicate that colestipol hydrochloride and cholestyramine can differ in their effects on the absorption of certain drugs from the GI tract of the rat [23].

Associations of UN2320 with other chemical compounds

• Complementarity of colestipol, niacin, and lovastatin in treatment of severe familial hypercholesterolemia [24].
• Comparative efficacy of colestipol and clofibrate in type IIa hyperlipoproteinemia [25].
• Biliary bile acid secretion is altered by a variety of drugs, including cheno- and ursodeoxycholic acids (CDCA and UCDA), the bile acid sequestrants cholestyramine and colestipol, and ethinyloestradiol [26].
• The combination of probucol and colestipol plus diet appears to be effective in treating most patients with familial hypercholesterolemia [27].
• Gemfibrozil serum elimination half-life was not significantly altered by combination with colestipol [28].

Gene context of UN2320

• CONCLUSION: Colestipol and lovastatin reduced CETP activity to the same amount, regardless of the apo E phenotype [29].
• Effects on plasma lipoproteins, lecithin:cholesterol acyltransferase (LCAT), and postheparin lipase (LPL and HTGL) activities were studied in 18 patients with familial hypercholesterolemia during 8-week treatment periods with colestipol (15 g/d), fenofibrate (0.25 g/d), and colestipol plus fenofibrate [30].
• Reductase mRNA decayed with a half-life of 2.5 h when mevinolin, a potent inhibitor of HMG-CoA reductase, and colestipol, a bile acid sequesterant, were removed from the diet of hypophysectomized rats [31].
• In the adult mouse, dietary cholesterol or colestipol induce cholesterol 7alpha-hydroxylase mRNA levels but do not affect oxysterol 7alpha-hydroxylase enzyme activity, mRNA, or protein levels [32].
• Feeding of rats with the bile-acid-sequestering anion-exchange resin colestid resulted in a pronounced stimulation of cholesterol 7 alpha-hydroxylase activity and bile acid mass production, but decreased the perivenous/periportal ratio of both parameters [33].

Analytical, diagnostic and therapeutic context of UN2320

• Electron microscopy revealed that LDL particles were smaller in size and analytical ultracentrifugation demonstrated that colestipol therapy selectively depleted larger, more buoyant LDL particles of Sf degrees 6-7 [34].
• Twenty-two patients suffering from hyperlipidemia and receiving therapy consisting of a lipid-lowering diet and clofibrate (1 g X 2) were in addition given colestipol hydrochloride (5 g X 3) (Colestid, Upjohn) in a randomized, cross-over study for 2 periods of 6 weeks [35].
• The bile acid resin binding agent Colestid improves diarrhea induced by enteral feeding [36].
• The purpose of this study was to investigate and compare the efficacy, safety, and patient acceptability of a new formulation of colestipol, colestipol tablets (T), with those of colestipol granules (G), in a randomized, double-blind, placebo-controlled, multicenter study [37].
• The effect of equivalent hypolipidaemic doses of cholestyramine (8 g) or colestipol (10 g) on the plasma concentrations of propranolol and 4'-hydroxypropranolol was studied in 12 normal volunteers following the oral administration of 120 mg of normal release propranolol tablets [38].

References