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Description

Colesevelam (trade name Welchol) a non-absorbed, polymeric, lipid-lowering agent intended for oral administration. Colesevelam is poly(allylamine hydrochloride) cross-linked with epichlorohydrin and alkylated with 1-bromodecane and (6-bromohexyl)-trimethylammonium bromide. Colesevelam hydrochloride is a hydrophilic, water-insoluble polymer that is not hydrolyzed by digestive enzymes and is not absorbed. Colesevelam is part of a class of drugs known as bile acid sequestrants. Colesevelam hydrochloride, the active pharmaceutical ingredient in Welchol, 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-α-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, HMG-CoA reductase, and increasing the number of hepatic LDL receptors. These compensatory effects result in increased clearance of LDL-C from the blood, resulting in decreased serum LDL-C levels. Colesevelam is indicated as an adjunct to diet and exercise to reduce elevated low-density lipoprotein cholesterol (LDL-C) in patients with primary hyperlipidemia as monotherapy and to improve glycemic control in adults with type 2 diabetes mellitus, including in combination with a statin. The expanded use of colesevelam in adults with type 2 diabetes mellitus is an example of drug repositioning.

CNS Activity

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions
PubMed

PubMed

TitleDatePubMed
Coadministration of colesevelam hydrochloride with atorvastatin lowers LDL cholesterol additively.
2001 Oct
Effects of colesevelam hydrochloride on low-density lipoprotein cholesterol and high-sensitivity C-reactive protein when added to statins in patients with hypercholesterolemia.
2006 Apr 15
Lipid-lowering effects of colesevelam HCl in combination with ezetimibe.
2006 Nov
Colesevelam hydrochloride in clinical practice: a new approach in the treatment of hypercholesterolaemia.
2008 Apr
Colesevelam HCl improves glycemic control and reduces LDL cholesterol in patients with inadequately controlled type 2 diabetes on sulfonylurea-based therapy.
2008 Aug
Modulating LDL cholesterol and glucose in patients with type 2 diabetes mellitus: targeting the bile acid pathway.
2008 Sep
Xanthomas associated with homozygous familial hypercholesterolemia.
2009 Dec
A 50-week extension study on the safety and efficacy of colesevelam in adults with primary hypercholesterolemia.
2010
Treatment with high-dose simvastatin inhibits geranylgeranylation in AML blast cells in a subset of AML patients.
2012 Mar
Patents

Patents

Sample Use Guides

In Vivo Use Guide
WELCHOL Tablets: The recommended dose is 6 tablets once daily or 3 tablets twice daily. WELCHOL Tablets should be taken with a meal and liquid WELCHOL for Oral Suspension: The recommended dose is one 3.75 gram packet once daily or one 1.875 gram packet twice daily.
Route of Administration: Oral
In Vitro Use Guide
A clinically relevant dose level of each study drug was incubated for 1 hour with and without colesevelam (or choletyramine for the subset of 4 drugs) in the 3 dissolution test media. Dissolution baths (900 mL) were used to consistently maintain the pH, temperature (37C), and stirring speed (200 rpm). After the 1-hour incubation, preparations were filtered to remove resin and any bound drug. The amount of drug remaining in the filtrate was primarily quantified using UV-visible spectrophotometry.
Name Type Language
COLESEVELAM
EMA EPAR   INN   VANDF   WHO-DD  
INN  
Official Name English
COLESEVELAM [INN]
Common Name English
2-PROPEN-1-AMINE POLYMER WITH (CHLOROMETHYL)OXIRANE, N,N,N-TRIMETHYL-6-(2-PROPENYLAMINO)-1-HEXANAMINIUM CHLORIDE, AND N-2-PROPENYL-1-DECANAMINE
Common Name English
COLESEVELAM [EMA EPAR]
Common Name English
COLESEVELAM [WHO-DD]
Common Name English
COLESEVELAM [VANDF]
Common Name English
ALLYLAMINE POLYMER WITH 1-CHLORO-2,3-EPOXYPROPANE, (6-(ALLYLAMINO)HEXYL)TRIMETHYLAMMONIUM CHLORIDE AND N-ALLYLDECYLAMINE
Common Name English
Classification Tree Code System Code
NDF-RT N0000180292
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
NDF-RT N0000175365
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
WHO-VATC QC10AC04
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
LIVERTOX 235
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
WHO-ATC C10AC04
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
Code System Code Type Description
MESH
C107058
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
PRIMARY
PUBCHEM
56843207
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
PRIMARY SWITZERF
WIKIPEDIA
COLESEVELAM
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
PRIMARY
HSDB
182815-43-6
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
PRIMARY
LactMed
182815-43-6
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
PRIMARY
CAS
182815-43-6
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
PRIMARY
RXCUI
141626
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
PRIMARY RxNorm
DRUG BANK
DB00930
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
PRIMARY
NCI_THESAURUS
C78056
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
PRIMARY
INN
7621
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
PRIMARY
EVMPD
SUB01423MIG
Created by admin on Tue Mar 06 11:22:32 UTC 2018 , Edited by admin on Tue Mar 06 11:22:32 UTC 2018
PRIMARY
Display Structure of COLESEVELAM