Repositioning Candidate Details
| Candidate ID: | R0135 |
| Source ID: | DB00375 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Colestipol |
| Synonyms: | Colestipol; Copolymer of bis(2-aminoethyl)amine and 2-(chloromethyl)oxirane; Epichlorohydrin-tetraethylenepentamine polymer |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | Bile acid sequestrants like colestipol have been in use since the 1970s. And even though such an agent may very well be useful in reducing elevated cholesterol levels and decreasing the risk for atherosclerotic vascular disease due to hypercholesterolemia, colestipol is still generally only employed as an adjunct therapy and the relatively physical nature of its pharmacological activity sometimes limits its usefulness. In particular, as colestipol's general mechanism of action ultimately results in the decreased absorption and enhanced secretion of bile acids and lipids in the feces, patients who take complicated medication regimens, experience constipation or biliary obstruction, etc. may not be good candidates for using the agent owing to its physical effects on the gut. Alternatively, colestipol predominantly elicits its activities within the gut environment because it undergoes little absorption and metabolism. The resultant lack of systemic exposure consequently means the medication generally demonstrates very few adverse effects inside the body. |
| CAS Number: | 26658-42-4 |
| Molecular Weight: | |
| DrugBank Indication: | Colestipol is indicated as adjunctive therapy to diet for the reduction of elevated serum total and low-density lipoprotein cholesterol (LDL-C) in patients with primary hypercholesterolemia (a condition that features elevated LDL-C) who do not respond adequately to dietary changes . Therapy with lipid-altering agents like colestipol should be a component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia . Treatment should begin and continue with dietary therapy . In general, a minimum of six months of intensive dietary therapy and counseling should be carried out prior to initiation of drug therapy such as that with colestipol . Shorter periods may be considered in patients with severe elevations of LDL-C or with definite coronary heart disease . Although colestipol is effective in all types of hypercholesterolemia, some regional prescribing information note in particular that it is medically most appropriate in patients with Fredrickson's type II hyperlipoproteinemia . Nevertheless, in patients with combined hypercholesterolemia and hypertriglyceridemia, although colestipol may be helpful in reducing elevated cholesterol, it is not formally indicated where hypertriglyceridemia is the abnormality of greatest concern . |
| DrugBank Pharmacology: | Cholesterol is the major, and probably the sole precursor of bile acids . During normal digestion, bile acids are secreted via the bile from the liver and gall bladder into the intestines . Bile acids emulsify the fat and lipid materials present in food, thus facilitating absorption . A major portion of the bile acids secreted is reabsorbed from the intestines and returned via the portal circulation to the liver, thus completing the enterohepatic cycle . Only very small amounts of bile acids are found in normal serum . Colestipol hydrochloride binds bile acids in the intestine forming a complex that is excreted in the feces . This nonsystemic action results in a partial removal of the bile acids from the enterohepatic circulation, preventing their reabsorption . Since colestipol hydrochloride is an anion exchange resin, the chloride anions of the resin can be replaced by other anions, usually those with a greater affinity for the resin than the chloride ion . |
| DrugBank MoA: | Colestipol is a lipid-lowering polymer that binds with bile acids in the intestine forming a complex that is excreted in the feces . This non-systemic action results in a continuous, partial removal of bile acids from the enterohepatic circulation preventing their reabsorption . This increased fecal loss of bile acids due to colestipol hydrochloride administration leads to increased oxidation of cholesterol to bile acids . This results in an increase in the number of hepatic low-density lipoprotein (LDL) receptors, and consequently an increased uptake of LDL and a decrease in serum/plasma beta lipoprotein or total and LDL cholesterol levels . Although hydrochloride produces an increase in the hepatic synthesis of cholesterol in man, serum cholesterol levels fall . |
| Targets: | Bile acids binder |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I11 | 5295 | Intestinal disease | A gastrointestinal system disease that is located_in the intestine. http://en.wikipedia.org/wiki/Human_gastrointestinal_tract | disease of anatomical entity/gastrointestinal system disease | Details |
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |