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Identification
Name Colestipol
Accession Number DB00375 (APRD00884)
Type small molecule
Groups approved
Description

Highly crosslinked and insoluble basic anion exchange resin used as anticholesteremic. It may also may reduce triglyceride levels. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Colestipolum [INN-Latin]
Brand names
  • Cholestabyl
  • Colestid
Brand name mixtures Not Available
Categories
  • Anion Exchange Resins
  • Antilipemic Agents
CAS number 50925-79-6
Weight Average: 281.826
Monoisotopic: 281.198238250
Chemical Formula C11H28ClN5O
InChI Key InChIKey=GMRWGQCZJGVHKL-UHFFFAOYSA-N
InChI
InChI=1S/C8H23N5.C3H5ClO/c9-1-3-11-5-7-13-8-6-12-4-2-10;4-1-3-2-5-3/h11-13H,1-10H2;3H,1-2H2
Plain Text
IUPAC Name
(2-aminoethyl)[2-({2-[(2-aminoethyl)amino]ethyl}amino)ethyl]amine; 2-(chloromethyl)oxirane
SMILES
ClCC1CO1.NCCNCCNCCNCCN
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Aliphatic and Aryl Amines
Substructures
  • Aliphatic and Aryl Amines
  • Ethers
  • Alkyl Halides
  • Heterocyclic compounds
  • Epoxides
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.
Pharmacodynamics 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.
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.
Volume of distribution Not Available
Protein binding Not applicable (not hydrolyzed by digestive enzymes and not absorbed).
Metabolism

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.
Half life Not Available
Clearance Not Available
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
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
  • Impax laboratories inc
Packagers
Dosage forms
Form Route Strength
Granule Oral
Tablet Oral
Prices
Unit description Cost Unit
Colestid 90 5 gm Packets Box 252.5 USD box
Colestid 30 5 gm Packets Box 81.11 USD box
Colestid Flavored 5 gm/7.5 gm Packets 3.29 USD packet
Colestid 5 g Powder Packet 1.04 USD packet
Colestid Orange 5 g Powder Packet 1.04 USD packet
Colestid 1 gm tablet 0.86 USD tablet
Colestipol hcl 1 gm tablet 0.66 USD tablet
Colestid 5 gm Granules 0.33 USD gm
Colestid Flavored 5 gm Granules 0.31 USD gm
Colestid flavored granules 0.3 USD g
Colestid 1 g Tablet 0.29 USD tablet
Patents
Country Patent Number Approved Expires
United States 5490987 1993-02-13 2013-02-13
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility Insoluble PhysProp
logP -2.206 PhysProp
Predicted Properties
Property Value Source
water solubility ALOGPS
logP ALOGPS
logP -2.52 ChemAxon Molconvert
logS ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 5 ChemAxon Molconvert
polar surface area 88.13 ChemAxon Molconvert
rotatable bond count 11 ChemAxon Molconvert
refractivity 56.04 ChemAxon Molconvert
polarizability 23.97 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C06925 Link_out
PubChem Compound 62816 Link_out
PubChem Substance 46505777 Link_out
ChemSpider 56550 Link_out
PharmGKB PA449096 Link_out
Drug Product Database 642975 Link_out
RxList http://www.rxlist.com/cgi/generic/colestipol.htm Link_out
Drugs.com http://www.drugs.com/cdi/colestipol.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/col1094.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Colestipol Link_out
ATC Codes
  • C10AC02
AHFS Codes
  • 24:06.04
PDB Entries Not Available
FDA label Not Available
MSDS show (53.5 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take with food.
Targets

1. Bile acids

Pharmacological action: yes
Actions: binder

References:
  1. LaRosa JC: The mechanism of action of lipid-lowering drugs. Angiology. 1982 Sep;33(9):562-76. Pubmed
  2. Farmer JA, Gotto AM Jr: Currently available hypolipidaemic drugs and future therapeutic developments. Baillieres Clin Endocrinol Metab. 1995 Oct;9(4):825-47. Pubmed
  3. Reiner Z: Combined therapy in the treatment of dyslipidemia. Fundam Clin Pharmacol. 2010 Feb;24(1):19-28. Epub 2009 Aug 14. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on December 21, 2010 15:47

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