DT-Web

DB00375 - Colestipol


Identification
Name Colestipol
Accession Number DB00375 (APRD00884)
Type small molecule
Description Highly crosslinked and insoluble basic anion exchange resin used as anticholesteremic. It may also may reduce triglyceride levels. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 281.826
Groups approved
Monoisotopic Weight 281.19823825
Pharmacology
Indication For use, as adjunctive therapy to diet, for the reduction of elevated serum total and LDL-C in patients with primary hypercholesterolemia (elevated LDL-C) who do not respond adequately to diet.
Mechanism of action Colestipol is a non-absorbed, lipid-lowering polymer that binds bile acids in the intestine, impeding their reabsorption. As the bile acid pool becomes depleted, the hepatic enzyme, cholesterol 7-(alpha)-hydroxylase, is upregulated, which increases the conversion of cholesterol to bile acids. This causes an increased demand for cholesterol in the liver cells, resulting in the dual effect of increasing transcription and activity of the cholesterol biosynthetic enzyme, hydroxymethyl-glutaryl-coenzyme A (HMG-CoA) reductase, and increasing the number of hepatic low-density lipoprotein (LDL) receptors. These compensatory effects result in increased clearance of LDL cholesterol (LDL-C) from the blood, resulting in decreased serum LDL-C levels. Serum triglyceride levels may increase or remain unchanged. The end result is increased clearance of LDL-cholesterol from the blood with decreased serum LDL-cholesterol.
Absorption Not absorbed from the gastrointestinal tract.
Protein binding Not applicable (not hydrolyzed by digestive enzymes and not absorbed).
Biotransformation Not applicable (not hydrolyzed by digestive enzymes and not absorbed).
Route of elimination Colestipol hydrochloride binds bile acids in the intestine forming a complex that is excreted in the feces. In humans, less than 0.17% of a single 14C-labeled colestipol hydrochloride dose is excreted in the urine when given following 60 days of chronic dosing of 20 grams of colestipol hydrochloride per day. The increased fecal loss of bile acids due to colestipol hydrochloride administration leads to an increased oxidation of cholesterol to bile acids.
Toxicity Oral LD50 in rats is > 1000 mg/kg. Symptoms of overdose may include eye irritation, constipation, abdominal cramps, nausea, vomiting, diarrhea, and hypersensitivity. However, as colestipol is not absorbed, the risk of systemic toxicity is low.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Acenocoumarol The bile acid sequestrant, colestipol, may decrease the anticoagulant effect of acenocoumarol by decreasing its absorption.
Anisindione The bile acid sequestrant, colestipol, may decrease the anticoagulant effect of anisindione by decreasing its absorption.
Chlorothiazide Bile acid sequestrants may decrease the absorption of thiazide diuretics such as chlorothiazide. The diuretic response is likewise decreased. Monitor for decreased therapeutic effects of thiazide diuretics if coadministered with a bile acid sequestrant. If these agents are used concomitantly, separate doses 2 or more hours to minimize the interaction.
Cholecalciferol Bile acid sequestrants such as colestipol may decrease the serum concentration of Vitamin D analogs such as cholecalciferol. More specifically, bile acid sequestrants may impair absorption of Vitamin D analogs. Avoid concomitant administration of vitamin D analogs and bile acid sequestrants. Monitor plasma calcium concentrations in patients receiving combined therapy with these agents. This is particularly important in patients receiving higher doses of a bile acid sequestant (i.e., 30 g/day or more of cholestyramine or equivalent) or in patients experiencing bile acid sequestrant-induced steatorrhea. Specific recommendations regarding the separation of administration of these agents are not defined; however, it would seem prudent to separate the administration of these agents by several hours to minimize the potential risk of interaction. Similar precautions do not apply to parenterally administered vitamin D analogs.
Dicumarol The bile acid sequestrant, colestipol, may decrease the anticoagulant effect of dicumarol by decreasing its absorption.
Digoxin The resin decreases the effect of digoxin
Fluvastatin Increased/decreased effect according to spacing
Hydrocortisone Cholestyramine decreases the effect of hydrocortisone
Levothyroxine The resin, colestipol, decreases the absorption of the thyroid hormone, levothyroxine.
Liothyronine The resin, colestipol, decreases the absorption of the thyroid hormone, liothyronine.
Liotrix The resin, colestipol, decreases the absorption of the thyroid hormone, liotrix.
Lomitapide Bile acid sequestrants also used for treating high cholesterol may interfere with the absorption of oral medications, thus separate administration by 4 hours.
Raloxifene The resin decreases the effect of raloxifene
Sulindac The bile acid sequestrant, colestipol, may decrease the absorption of the NSAID, sulindac. Monitor for changes in the therapeutic and adverse effects of sulindac if colestipol is initiated, discontinued or dose changed. Administering the two agents 2 or more hours apart may reduce, but not eliminate, the risk of this interactions.
Thyroglobulin The resin, colestipol, decreases the absorption of the thyroid hormone, thyroglobulin.
Tiaprofenic acid The bile acid sequestrant, Colestipol, may reduce Tiaprofenic acid absorption and therapeutic effect.
Tolmetin Colestipol may decrease the absorption of Tolmetin. Monitor for changes in the therapeutic and adverse effects of Tolmetin if Colestipol is initiated, discontinued or dose changed. Spacing administration by at least 2 hours may reduce the risk of interaction.
Torasemide Colestipol may decrease the bioavailability of Torasemide by inhibiting Torasemide absorption. Monitor for changes in the therapeutic and adverse effects of Torasemide if Colestipol is initiated, discontinued or dose changed. Spacing administration by at least 2 hours may reduce the risk of interaction.
Trichlormethiazide The bile acid sequestrant, Colestipol, may inhibit the absorption of Trichlormethiazide.
Ursodeoxycholic acid The resin decreases the effect of ursodiol
Warfarin The bile acid sequestrant, colestipol, may decrease the anticoagulant effect of warfarin by decreasing its absorption.
Food Interactions
  • Take with food.

Targets


Bile acids
Name Bile acids
Gene Name Not Available
Pharmacological action yes
Actions binder
References
  • LaRosa JC: The mechanism of action of lipid-lowering drugs. Angiology. 1982 Sep;33(9):562-76. - Pubmed
  • Farmer JA, Gotto AM Jr: Currently available hypolipidaemic drugs and future therapeutic developments. Baillieres Clin Endocrinol Metab. 1995 Oct;9(4):825-47. - Pubmed
  • Reiner Z: Combined therapy in the treatment of dyslipidemia. Fundam Clin Pharmacol. 2010 Feb;24(1):19-28. Epub 2009 Aug 14. - Pubmed
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
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