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Identification
NameCrofelemer
Accession NumberDB04941
TypeSmall Molecule
GroupsApproved
Description

Crofelemer, previously known as the investigational drug SP-303, is a novel proanthocyanidin purified from the bark latex of the Amazonian Croton tree Croton lechleri. It is marketed under the brand name Fulyzaq and indicated for the symptomatic treatment of non-infectious diarrhea in adult patients with HIV/AIDS who are taking antiretroviral therapy.

Structure
Thumb
Synonyms
SynonymLanguageCode
ProvirNot AvailableNot Available
SP-303Not AvailableNot Available
SaltsNot Available
Brand names
NameCompany
FulyzaqSALIX PHARMS
Brand mixturesNot Available
CategoriesNot Available
CAS number148465-45-6
WeightNot Available
Chemical FormulaNot Available
InChI KeyNot Available
InChINot Available
IUPAC NameNot Available
SMILESNot Available
Mass SpecNot Available
Taxonomy
KingdomNot Available
SuperclassNot Available
ClassNot Available
SubclassNot Available
Direct parentNot Available
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
IndicationFor the symptomatic treatment of non-infectious diarrhea in adult patients with HIV/AIDS who are taking antiretroviral therapy.
PharmacodynamicsCrofelemer is an inhibitor of secretory diarrhea via inhibition of the CFTR chloride transporter. Crofelemer is not an antimicrobial, and therefore does not drive the emergence of resistance; it does not inhibit motility, and therefore does not cause constipation or rebound diarrhea; and it is not systemically absorbed, reducing the potential for adverse drug interactions and toxicity.
Mechanism of actionCrofelemer is an inhibitor of the cystic fibrosis transmembrane regulator chloride channel (CFTR), as evidenced by its activity on cell cultures, single cell patch clamps, single CFTR channels, and elaboration of mouse intestinal fluid secretion. Crofelemer also inhibits calcium activated chloride channels (CaCC), which in combination with CFTR, are expressed on the luminal side of intestinal cells. Crofelemer inhibition of both of these channels prevents water loss from diarrhea by inhibiting chloride secretion.
AbsorptionThe absorption of crofelemer is minimal and crofelemer concentrations in plasma are below the level of quantitation (50 ng/mL).
Volume of distribution

Since crofelemer is not significantly absorbed, volume of distribution was not quantified.

Protein bindingSince crofelemer is not significantly absorbed, protein binding was not quantified.
Metabolism

Since crofelemer is not significantly absorbed, no metabolites have been identified.

Route of eliminationSince crofelemer is not significantly absorbed, the route of elimination has not been identified.
Half lifeSince crofelemer is not significantly absorbed, the half life was not determined.
Clearance

Since crofelemer is not significantly absorbed, clearance was not determined.

ToxicityThe most common adverse effects are cough, flatulence, upper respiratory tract infection, bronchitis, and increased bilirubin.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption Not Available Not Available
Blood Brain Barrier Not Available Not Available
Caco-2 permeable Not Available Not Available
P-glycoprotein substrate Not Available Not Available
P-glycoprotein inhibitor I Not Available Not Available
P-glycoprotein inhibitor II Not Available Not Available
Renal organic cation transporter Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 1A2 substrate Not Available Not Available
CYP450 2C9 substrate Not Available Not Available
CYP450 2D6 substrate Not Available Not Available
CYP450 2C19 substrate Not Available Not Available
CYP450 3A4 substrate Not Available Not Available
CYP450 inhibitory promiscuity Not Available Not Available
Ames test Not Available Not Available
Carcinogenicity Not Available Not Available
Biodegradation Not Available Not Available
Rat acute toxicity Not Available Not applicable
hERG inhibition (predictor I) Not Available Not Available
hERG inhibition (predictor II) Not Available Not Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tablet, delayed releaseOral125MG
PricesNot Available
Patents
CountryPatent NumberApprovedExpires (estimated)
United States7,341,7442000-11-142020-11-14
Properties
Statesolid
Experimental PropertiesNot Available
Predicted PropertiesNot Available
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Crutchley RD, Miller J, Garey KW: Crofelemer, a novel agent for treatment of secretory diarrhea. Ann Pharmacother. 2010 May;44(5):878-84. doi: 10.1345/aph.1M658. Epub 2010 Apr 13. Pubmed
  2. FDA label.
External Links
ResourceLink
KEGG DrugD03605
RxListhttp://www.rxlist.com/fulyzaq-drug.htm
Drugs.comhttp://www.drugs.com/sfx/crofelemer-side-effects.html
WikipediaCrofelemer
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(357 KB)
MSDSshow(566 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Cystic fibrosis transmembrane conductance regulator

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Cystic fibrosis transmembrane conductance regulator P13569 Details

References:

  1. Tradtrantip L, Namkung W, Verkman AS: Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol Pharmacol. 2010 Jan;77(1):69-78. doi: 10.1124/mol.109.061051. Epub 2009 Oct 6. Pubmed

2. Anoctamin-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Anoctamin-1 Q5XXA6 Details

References:

  1. Tradtrantip L, Namkung W, Verkman AS: Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol Pharmacol. 2010 Jan;77(1):69-78. doi: 10.1124/mol.109.061051. Epub 2009 Oct 6. Pubmed

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Drug created on October 21, 2007 16:23 / Updated on June 07, 2013 22:00