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Colestipol

PubChem Reference Collection SID
PubChem CID
Not available and might not be a discrete structure.
Structure
Colestipol_small.png
Synonyms
  • Colestipol
  • 50925-79-6
  • Colestipolum
  • K50N755924
  • Epichlorohydrin-tetraethylenepentamine polymer
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.
Colestipol is a Bile Acid Sequestrant. The mechanism of action of colestipol is as a Bile-acid Binding Activity.
Colestipol is a nonabsorbed bile acid sequestrant that is used a therapy of hyperlipidemia and for the pruritus of chronic liver disease and biliary obstruction. Colestipol has not been associated with clinically apparent liver injury.
See also: Epichlorohydrin (has monomer); Diethylenetriamine (has monomer); Colestipol Hydrochloride (has salt form).

1 Synonyms

  • Colestipol
  • 50925-79-6
  • Colestipolum
  • K50N755924
  • Epichlorohydrin-tetraethylenepentamine polymer
  • CHEBI:3814
  • 1,2-Ethanediamine, N-(2-aminoethyl)-N'-(2-((2-aminoethyl)amino)ethyl)-, polymer with (chloromethyl)oxirane
  • C10AC02
  • COPOLYMER OF DIETHYLENETRIAMINE AND 1-CHLORO-2,3-EPOXYPROPANE
  • Colestipolum (INN-Latin)
  • Copolymer of bis(2-aminoethyl)amine and 2-(chloromethyl)oxirane
  • Epichlorohydrin, polymer with tetraethylenepentamine
  • Epichlorohydrin, tetraethylenepentamine polymer
  • Epichlorohydrin-tetraethylenepentamine copolymer
  • NSC 147003
  • NSC-147003
  • Oxirane, (chloromethyl)-, polymer with N-(2-aminoethyl)-N'-(2-((2-aminoethyl)amino)ethyl-1,2-ethanediamine
  • POLY(EPICHLOROHYDRIN-CO-TETRAETHYLENEPENTAMINE)
  • Propane, 1-chloro-2,3-epoxy-, polymer with tetraethylenepentamine
  • Tetraethylenepentamine epichlorohydrin polymer
  • Tetraethylenepentamine, cross-linked with epichlorohydrin
  • Tetraethylenepentamine, polymer with 1-chloro-2,3-epoxypropane
  • Tetraethylenepentamine-epichlorohydrin copolymer
  • Tetraethylenepentamine-epichlorohydrin polymer
  • U 26597A
  • UNII-K50N755924

2 Structures

2.1 2D Structure

Chemical Structure Depiction
Colestipol.png

3 Names and Identifiers

3.1 Other Identifiers

3.1.1 CAS

26658-42-4

3.1.2 NSC Number

3.1.3 UNII

3.1.4 DSSTox Substance ID

3.1.5 NCI Thesaurus Code

3.1.6 RXCUI

4 Chemical and Physical Properties

4.1 Experimental Properties

4.1.1 Solubility

Insoluble

4.1.2 LogP

-2.206

6 Drug and Medication Information

6.1 Drug 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.

6.2 LiverTox Summary

Colestipol is a nonabsorbed bile acid sequestrant that is used a therapy of hyperlipidemia and for the pruritus of chronic liver disease and biliary obstruction. Colestipol has not been associated with clinically apparent liver injury.

6.3 Drug Classes

Breast Feeding; Lactation; Milk, Human; Anticholesteremic Agents; Antilipemic Agents
Antilipemic Agents

7 Pharmacology and Biochemistry

7.1 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.

7.2 FDA Pharmacological Classification

FDA UNII
K50N755924
Active Moiety
COLESTIPOL
Pharmacological Classes
Established Pharmacologic Class [EPC] - Bile Acid Sequestrant
Pharmacological Classes
Mechanisms of Action [MoA] - Bile-acid Binding Activity
FDA Pharmacology Summary
Colestipol is a Bile Acid Sequestrant. The mechanism of action of colestipol is as a Bile-acid Binding Activity.

7.3 ATC Code

C - Cardiovascular system

C10 - Lipid modifying agents

C10A - Lipid modifying agents, plain

C10AC - Bile acid sequestrants

C10AC02 - Colestipol

7.4 Absorption, Distribution and Excretion

Absorption
Colestipol is hydrophilic, but it is virtually water-insoluble (99.75%). This water insolubility, combined with the high molecular weight polymer in colestipol basically means the agent and the complexes it forms when it binds with bile acids are not absorbed. The action of colestipol is ultimately limited to the lumen of the gastrointestinal tract. It binds bile acids in the intestinal lumen and causes them to be excreted in the feces together with the polymer. When the enterohepatic circulation of bile acids is interrupted, cholesterol conversion to bile acids is enhanced and plasma cholesterol levels are thereby lowered.
Route of Elimination
Colestipol hydrochloride binds bile acids in the intestine forming a complex that is then ultimately 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 increased oxidation of cholesterol to bile acids.
Volume of Distribution
Colestipol is not absorbed into the systemic circulation.

7.5 Metabolism / Metabolites

Colestipol is not absorbed into the systemic circulation nor is it hydrolyzed by any digestive enzymes.

7.6 Biological Half-Life

Colestipol is not absorbed into the systemic circulation nor is it hydrolyzed by any digestive enzymes. Its action is ultimately limited to the lumen of the gastrointestinal tract, where it is eventually passed into the feces.

7.7 Mechanism of Action

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.

8 Toxicity

8.1 Toxicological Information

8.1.1 Hepatotoxicity

There is little evidence that colestipol causes liver injury. Mild elevations in serum aminotransferase and alkaline phosphatase levels have been reported in small numbers of patients on bile acid resins, although the elevations have been mild, transient and without accompanying symptoms. In addition, a case report of more marked aminotransferase elevations (>10 times ULN) with rapid recovery on stopping colestipol has been published, but the mechanism by which it might cause hepatotoxicity is very unclear. Colestipol is used in patients with liver disease to treat pruritus, and has little or no effect on serum enzyme or bilirubin levels.

Likelihood score: E (unlikely cause of clinically apparent liver injury with jaundice).

8.1.2 Drug Induced Liver Injury

Compound
colestipol
DILI Annotation
Ambiguous DILI-concern
Severity Grade
3
Label Section
Adverse reactions
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

8.1.3 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Colestipol is a nonabsorbable resin. Because it does not enter the mother's bloodstream, it will not reach the infant via breastmilk. It is acceptable for use during lactation.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

8.1.4 Protein Binding

Colestipol is not absorbed into the systemic circulation.

9 Patents

10 Interactions and Pathways

10.1 Drug-Drug Interactions

10.2 Drug-Food Interactions

  • Drink plenty of fluids. The tablet and granule formulations must be taken with plenty of water or other fluids.
  • Take with food.

11 Information Sources

  1. PubChem Reference Collection
  2. PubChem
  3. CAS Common Chemistry
    LICENSE
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    https://creativecommons.org/licenses/by-nc/4.0/
  4. ChemIDplus
  5. DrugBank
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    https://www.drugbank.ca/legal/terms_of_use
  6. DTP/NCI
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  7. EPA DSSTox
    N~1~,N~1'~-[Azanediyldi(ethane-2,1-diyl)]di(ethane-1,2-diamine)--2-(chloromethyl)oxirane (1/1)
    https://comptox.epa.gov/dashboard/DTXSID00965206
  8. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  9. Drug Induced Liver Injury Rank (DILIrank) Dataset
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    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  10. FDA Pharm Classes
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  11. LiverTox
  12. NCI Thesaurus (NCIt)
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    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  13. Drugs and Lactation Database (LactMed)
  14. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  15. WHO Anatomical Therapeutic Chemical (ATC) Classification
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    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
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