Identification

Name
Crofelemer
Accession Number
DB04941
Type
Small Molecule
Groups
Approved
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.

Synonyms
  • Provir
  • SP-303
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FulyzaqTablet, coated125 mg/1OralSalix Pharmaceuticals2012-12-312017-11-01Us
MytesiTablet, coated125 mg/1OralNapo Pharmaceuticals, Inc.2016-04-12Not applicableUs
Categories
UNII
PY79D6C8RX
CAS number
148465-45-6
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

For the symptomatic treatment of non-infectious diarrhea in adult patients with HIV/AIDS who are taking antiretroviral therapy.

Structured Indications
Pharmacodynamics

Crofelemer 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 action

Crofelemer 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.

TargetActionsOrganism
ACystic fibrosis transmembrane conductance regulator
antagonist
Human
AAnoctamin-1
antagonist
Human
Absorption

The 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 binding

Since crofelemer is not significantly absorbed, protein binding was not quantified.

Metabolism

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

Route of elimination

Since crofelemer is not significantly absorbed, the route of elimination has not been identified.

Half life

Since crofelemer is not significantly absorbed, the half life was not determined.

Clearance

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

Toxicity

The most common adverse effects are cough, flatulence, upper respiratory tract infection, bronchitis, and increased bilirubin.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
  • Crofelemer is not affected by food.

References

General References
  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:20388859]
External Links
KEGG Drug
D03605
PubChem Substance
347909853
ChEMBL
CHEMBL2108184
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Crofelemer
FDA label
Download (357 KB)
MSDS
Download (566 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentColonic Diseases / Diarrhea / Gastrointestinal Diseases / Irritable Bowel Syndrome (IBS)1
2CompletedTreatmentIrritable Bowel Syndrome (IBS)1
2RecruitingPreventionCancer, Breast1
2RecruitingTreatmentHer2-Positive Breast Cancer1
3CompletedTreatmentDiarrhea With HIV / HIV Enteropathy1
3CompletedTreatmentDiarrhea / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHIV Associated Diarrhea1
Not AvailableCompletedTreatmentHerpes Simplex / Human Immunodeficiency Virus (HIV) Infections2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, coatedOral125 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7341744No2000-11-142020-11-14Us
US8962680No2011-10-312031-10-31Us
US8574634No1998-01-112018-01-11Us
US7323195No1998-06-072018-06-07Us
US9585868No2011-10-312031-10-31Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Pdz domain binding
Specific Function
Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO...
Gene Name
CFTR
Uniprot ID
P13569
Uniprot Name
Cystic fibrosis transmembrane conductance regulator
Molecular Weight
168139.895 Da
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:19808995]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Voltage-gated chloride channel activity
Specific Function
Calcium-activated chloride channel (CaCC) which plays a role in transepithelial anion transport and smooth muscle contraction. Required for the normal functioning of the interstitial cells of Cajal...
Gene Name
ANO1
Uniprot ID
Q5XXA6
Uniprot Name
Anoctamin-1
Molecular Weight
114077.215 Da
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:19808995]

Drug created on October 21, 2007 16:23 / Updated on November 06, 2017 06:45