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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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Fulyzaqtablet, coated125 mgoralSalix Pharmaceuticals, Inc.2012-12-31Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
CAS number148465-45-6
WeightNot Available
Chemical FormulaNot Available
InChI KeyNot Available
InChINot Available
IUPAC NameNot Available
SMILESNot Available
Taxonomy
ClassificationNot classified
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
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 2C19 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tablet, coatedoral125 mg
PricesNot Available
Patents
CountryPatent NumberApprovedExpires (estimated)
United States7,341,7442000-11-142020-11-14
Properties
StateSolid
Experimental PropertiesNot Available
Predicted PropertiesNot Available
Spectra
Mass Spec (NIST)Not Available
SpectraGC-MSMS/MSMS1D NMR2D NMR
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
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (357 KB)
MSDSDownload (566 KB)
Interactions
Drug Interactions
Drug
AripiprazoleCYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole.
DofetilideCYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide.
HydrocodoneCYP3A4 Inhibitors (Weak) may increase the serum concentration of Hydrocodone.
LomitapideCYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide.
PimozideCYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide.
Food Interactions
  • Crofelemer is not affected by food.

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