Secretin human

Identification

Summary

Secretin human is a secretin hormone used to stimulate pancreatic or gastric secretions to diagnose exocrine pancreas dysfunction, gastrinoma, and abnormalities in the bile and pancreatic ducts.

Brand Names
Chirhostim
Generic Name
Secretin human
DrugBank Accession Number
DB09532
Background

Human secretin is a gastrointestinal peptide hormone that regulates secretions in the stomach, pancreas, and liver. The hormone is produced from the enterochromaffin cells in the duodenum in response to the duodenal content with the pH less than 4.5 5. The main action of secretin is to stimulate the pancreas to secrete pancreatic juice for pH regulation in the small intestines. Secretin is also responsible in body fluid homeostasis 4 and bile production. Although it is a gastrointestinal hormone, secretin is also considered as a neuropeptide hormone since it is also expressed in the central nervous system 3.

Purified synthetic human secretin, also referred to as RG1068, is available as an intravenous injection under the market name ChiRhoStim ® in the U.S.. It contains an amino acid sequence identical to the naturally occurring hormone consisting of 27 amino acids Label that supports α-helical formation 3. The carboxyl-terminal amino acid, valine, is amidated. Synthetic human secretin displays equivalent biological activity and properties as naturally-occurring secretin 1. It is indicated for the stimulation of the pancreatic and gastric secretions to aid in the diagnosis of pancreatic exocrine dysfunction and the diagnosis of gastrinoma, and facilitate the identification of the ampulla of Vater and accessory papilla during endoscopic retrograde cholangiopancreatography (ERCP).

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Hormones
Protein Structure
Db09532
Protein Chemical Formula
C130H220N44O39
Protein Average Weight
3039.44 Da
Sequences
>Human Secretin
HSDGTFTSELSRLREGARLQRLLQGLV
Download FASTA Format
Synonyms
  • Human secretin
  • Secretin
  • Secretin (human)
  • Secretin human
  • Secretin synthetic human
  • Synthetic human secretin
External IDs
  • RG-1068
  • RG1068

Pharmacology

Indication

Indicated for the stimulation of:

  • pancreatic secretions, including bicarbonate, to aid in the diagnosis of pancreatic exocrine dysfunction Label.

  • gastrin secretion to aid in the diagnosis of gastrinoma Label.

  • pancreatic secretions to facilitate the identification of the ampulla of Vater and accessory papilla during endoscopic retrograde cholangiopancreatography (ERCP) Label.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

In clinical trials, intravenous administration of synthetic human secretin stimulated the exocrine pancreas to promote juice and bicarbonate secretion, with variable responses depending on the pancreatic function of the individual Label. Having an identical amino acid sequence to the biologically-derived secretin, synthetic human secretin exhibits an equivalent biological activity as the natural hormone. The biological activity of synthetic human secretin was approximately 5.0 CU per mcg Label. In patients with suspected or known exocrine pancreatic dysfunction, a volume response of less than 2 mL/kg/hr, peak bicarbonate concentration of less than 80 mEq/L, and a bicarbonate output of less than 0.2 mEq/kg/hr following intravenous synthetic human secretin Label. Administration in healthy subjects in three crossover studies led to overall pancreatic secretory response of a mean peak bicarbonate concentration of 100 mEq/L, a mean total volume over one hour of 260.7 mL, and a peak bicarbonate concentrations ≥ 80 mEq/L Label.

In a baseline-controlled study of patients with acute and acute recurrent pancreatitis undergoing magnetic resonance cholangiopancreatography (MRCP), administration of synthetic human secretin resulted in higher levels of sensitivity with minimal loss in specificity. This indicates that the stimulation of pancreatic secretions by synthetic secretin facilitates the diagnosis and clinical decision making of patients acute, acute recurrent, or chronic pancreatitis 2.

Mechanism of action

Synthetic human secretin mediates the same biological effects as the naturally-occurring gastrointestinal peptide hormone. Secretin is normally released from enterochromaffin cells and S cells in the intestinal mucosa of duodenum upon exposure of proximal intestinal lumen to the acidic gastric content, or fatty acids and amino acids Label. Secretin mediates an inhibitory effect on acid secretion by parietal cells of the stomach, and causes alkalinazation of the duodenal content by stimulating the release of pancreatic juice, which has high amounts of water and bicarbonate ions 5. Bicarbonate ions are released into the duodenum from the centroacinar cells, and epithelia lining the pancreatic and biliary ducts 3. Human secretin is a ligand at G-protein coupled secretin receptors which are expressed in the basolateral domain of several tissue cell types 3, including pancreas, stomach, liver, colon and other tissues Label. Upon interaction, levels of cAMP increase and initiates the cAMP-mediated signalling cascade that results in phosphorylation of protein kinase A (PKA) and activation of cystic fibrosis transmembrane conductance regulator (CFTR) 3. Activation of CFTR activates Cl-/HCO3- anion exchanger 2 and leads to secretion of bicarbonate-rich-pancreatic fluid 3. Via the same cAMP signalling pathway, secretin promotes the secretion of water and electrolytes in cholangiocytes 3. Secretin may work through vagal-vagal neural pathways since stimulation of the efferent vagus nerve stimulates bicarbonate secretion and atropine blocks secretin-stimulated pancreatic secretion Label. Additionally, secretin acts as a diuretic to increase urinary volume and bicarbonate excretion 3,4.

TargetActionsOrganism
ASecretin receptor
ligand
Humans
Absorption

Following intravenous bolus administration of 0.4 mcg/kg, synthetic human secretin concentration rapidly declines to baseline secretin levels within 90 to 120 minutes Label.

Volume of distribution

The volume of distribution is 2.7 L Label.

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

The elimination half life of synthetic human secretin is 45 minutes Label.

Clearance

The clearance of synthetic human secretin is 580.9 ± 51.3 mL/min Label.

Adverse Effects
Adverseeffects
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Toxicity

In acute toxicity studies with mice and rabbits, a dose of 20 μg/kg of synthetic human secretin was not lethal with no clinical symptoms of toxicity. The no-observed-effect level (NOEL) in rats was 10 μg/kg/day in a 14-day intravenous toxicity study without any evidence of adverse toxicity. The NOEL was 5 μg/kg/day in dogs 5.

Studies assessing the carcinogenic potential, mutagenicity, or potential for impairment of fertility have not been conducted with synthetic human secretin Label.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AclidiniumThe therapeutic efficacy of Secretin human can be decreased when used in combination with Aclidinium.
AmantadineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Amantadine.
AmitriptylineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Amitriptyline.
AmobarbitalThe therapeutic efficacy of Secretin human can be decreased when used in combination with Amobarbital.
AmoxapineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Amoxapine.
Anisotropine methylbromideThe therapeutic efficacy of Secretin human can be decreased when used in combination with Anisotropine methylbromide.
AripiprazoleThe therapeutic efficacy of Secretin human can be decreased when used in combination with Aripiprazole.
AtracuriumThe therapeutic efficacy of Secretin human can be decreased when used in combination with Atracurium.
Atracurium besylateThe therapeutic efficacy of Secretin human can be decreased when used in combination with Atracurium besylate.
AtropineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Atropine.
Interactions
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Secretin human pentahydrochloride7HP60U6HMM108072-62-4Not applicable
International/Other Brands
SecreFlo (Repligen Corp) / Secremax (Repligen Corp)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ChiRhoStimInjection, powder, lyophilized, for solution16 ug/8mLIntravenousChiRhoClin, Inc.2004-08-01Not applicableUS flag
ChiRhoStim 40Injection, powder, lyophilized, for solution40 ug/10mLIntravenousChiRhoClin, Inc.2007-06-01Not applicableUS flag
Secretin Inj 75unit/vialPowder, for solution75 unit / vialIntravenousFerring Pharmaceuticals1990-12-311999-08-04Canada flag

Categories

ATC Codes
V04CK01 — Secretin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
A0426J905J
CAS number
108153-74-8

References

General References
  1. Lankisch PG, Creutzfeldt W: Effect of synthetic and natural secretin on the function of the exocrine pancreas in man. Digestion. 1981;22(2):61-5. doi: 10.1159/000198596. [Article]
  2. Sherman S, Freeman ML, Tarnasky PR, Wilcox CM, Kulkarni A, Aisen AM, Jacoby D, Kozarek RA: Administration of secretin (RG1068) increases the sensitivity of detection of duct abnormalities by magnetic resonance cholangiopancreatography in patients with pancreatitis. Gastroenterology. 2014 Sep;147(3):646-654.e2. doi: 10.1053/j.gastro.2014.05.035. Epub 2014 Jun 4. [Article]
  3. Afroze S, Meng F, Jensen K, McDaniel K, Rahal K, Onori P, Gaudio E, Alpini G, Glaser SS: The physiological roles of secretin and its receptor. Ann Transl Med. 2013 Oct;1(3):29. doi: 10.3978/j.issn.2305-5839.2012.12.01. [Article]
  4. Chu JY, Cheng CY, Lee VH, Chan YS, Chow BK: Secretin and body fluid homeostasis. Kidney Int. 2011 Feb;79(3):280-7. doi: 10.1038/ki.2010.397. Epub 2010 Oct 13. [Article]
  5. 21-256 Synthetic Human Secretin Pharmacology Review - FDA [Link]
PubChem Substance
347827873
ChemSpider
17314768
RxNav
606396
ChEBI
135913
ChEMBL
CHEMBL3039582
FDA label
Download (98.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedDiagnosticSphincter of Oddi Dysfunction1
4RecruitingDiagnosticEndoscopic Retrograde Cholangiopancreatography (ERCP)1
3CompletedDiagnosticPancreatic Diseases1
3CompletedDiagnosticPancreatitis1
3CompletedTreatmentAutism, Early Infantile2
3Not Yet RecruitingDiagnosticAbdominal Pain / Irritable Bowel Syndrome (IBS)1
3RecruitingDiagnosticGene Mutations / Germline Mutation Carrier / Lynch Syndrome / Malignant Neoplasm of Pancreas / Peutz-Jeghers Syndrome (PJS)1
3TerminatedTreatmentAutism, Early Infantile1
2CompletedDiagnosticHealthy Subjects (HS) / Pancreatitis, Chronic1
2CompletedEducational/Counseling/TrainingObsessive Compulsive Disorder (OCD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous16 ug/8mL
Injection, powder, lyophilized, for solutionIntravenous40 ug/10mL
Injection, powder, lyophilized, for solutionIntravenous
Powder, for solutionIntravenous75 unit / vial
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Ligand
General Function
Secretin receptor activity
Specific Function
This is a receptor for secretin. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name
SCTR
Uniprot ID
P47872
Uniprot Name
Secretin receptor
Molecular Weight
50206.135 Da
References
  1. Miller LJ, Dong M, Harikumar KG: Ligand binding and activation of the secretin receptor, a prototypic family B G protein-coupled receptor. Br J Pharmacol. 2012 May;166(1):18-26. doi: 10.1111/j.1476-5381.2011.01463.x. [Article]
  2. Korner M, Hayes GM, Rehmann R, Zimmermann A, Friess H, Miller LJ, Reubi JC: Secretin receptors in normal and diseased human pancreas: marked reduction of receptor binding in ductal neoplasia. Am J Pathol. 2005 Oct;167(4):959-68. doi: 10.1016/S0002-9440(10)61186-8. [Article]

Drug created on November 30, 2015 19:10 / Updated on May 21, 2021 10:21