Identification

Name
Secretin human
Accession Number
DB09532  (BTD00039, BIOD00039, DB06369, DB00021)
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Hormones
Description

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).

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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ChiRhoStimInjection, powder, lyophilized, for solution16 ug/8mLIntravenousChi Rho Clin, Inc.2004-08-01Not applicableUs
ChiRhoStim 40Injection, powder, lyophilized, for solution40 ug/10mLIntravenousChi Rho Clin, Inc.2007-06-01Not applicableUs
Secretin Inj 75unit/vialPowder, for solution75 unitIntravenousFerring Pharmaceuticals1990-12-311999-08-04Canada
International/Other Brands
SecreFlo (Repligen Corp) / Secremax (Repligen Corp)
Categories
UNII
A0426J905J
CAS number
108153-74-8

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].

Associated Conditions
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
Human
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].

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].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AclidiniumThe therapeutic efficacy of Human secretin can be decreased when used in combination with Aclidinium.Approved
AgmatineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Agmatine.Experimental, Investigational
AlcuroniumThe therapeutic efficacy of Human secretin can be decreased when used in combination with Alcuronium.Experimental
Anisotropine MethylbromideThe therapeutic efficacy of Human secretin can be decreased when used in combination with Anisotropine Methylbromide.Approved
AtracuriumThe therapeutic efficacy of Human secretin can be decreased when used in combination with Atracurium.Approved, Experimental, Investigational
Atracurium besylateThe therapeutic efficacy of Human secretin can be decreased when used in combination with Atracurium besylate.Approved
AtropineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Atropine.Approved, Vet Approved
BenactyzineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Benactyzine.Withdrawn
BenzatropineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Benzatropine.Approved
BiperidenThe therapeutic efficacy of Human secretin can be decreased when used in combination with Biperiden.Approved, Investigational
BornaprineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Bornaprine.Experimental
BrompheniramineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Brompheniramine.Approved
BupropionThe therapeutic efficacy of Secretin human can be decreased when used in combination with Bupropion.Approved
ButylscopolamineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Butylscopolamine.Approved, Investigational, Vet Approved
ChlorphenoxamineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Chlorphenoxamine.Withdrawn
CyclopentolateThe therapeutic efficacy of Human secretin can be decreased when used in combination with Cyclopentolate.Approved
DarifenacinThe therapeutic efficacy of Human secretin can be decreased when used in combination with Darifenacin.Approved, Investigational
DesloratadineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Desloratadine.Approved, Investigational
DexetimideThe therapeutic efficacy of Human secretin can be decreased when used in combination with Dexetimide.Withdrawn
DextromethorphanThe therapeutic efficacy of Secretin human can be decreased when used in combination with Dextromethorphan.Approved
DicyclomineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Dicyclomine.Approved
DiphenhydramineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Diphenhydramine.Approved, Investigational
DoxylamineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Doxylamine.Approved, Vet Approved
EmeproniumThe therapeutic efficacy of Human secretin can be decreased when used in combination with Emepronium.Experimental
EtanautineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Etanautine.Experimental
EthopropazineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Ethopropazine.Approved
EtybenzatropineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Etybenzatropine.Experimental
FesoterodineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Fesoterodine.Approved
FlavoxateThe therapeutic efficacy of Human secretin can be decreased when used in combination with Flavoxate.Approved
FluoxetineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Fluoxetine.Approved, Vet Approved
GallamineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Gallamine.Experimental
Gallamine TriethiodideThe therapeutic efficacy of Human secretin can be decreased when used in combination with Gallamine Triethiodide.Approved
GlycopyrroniumThe therapeutic efficacy of Human secretin can be decreased when used in combination with Glycopyrronium.Approved, Investigational, Vet Approved
HomatropineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Homatropine.Approved
HyoscyamineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Hyoscyamine.Approved
IpratropiumThe therapeutic efficacy of Secretin human can be decreased when used in combination with Ipratropium.Approved
LamotrigineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Lamotrigine.Approved, Investigational
MazaticolThe therapeutic efficacy of Human secretin can be decreased when used in combination with Mazaticol.Experimental
MecamylamineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Mecamylamine.Approved, Investigational
MethanthelineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Methantheline.Approved, Investigational
MethscopolamineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Methscopolamine.Approved
Methylscopolamine bromideThe therapeutic efficacy of Human secretin can be decreased when used in combination with Methylscopolamine bromide.Approved
MetixeneThe therapeutic efficacy of Human secretin can be decreased when used in combination with Metixene.Approved
NicardipineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Nicardipine.Approved, Investigational
OrphenadrineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Orphenadrine.Approved
OtiloniumThe therapeutic efficacy of Secretin human can be decreased when used in combination with Otilonium.Experimental, Investigational
OxitropiumThe therapeutic efficacy of Human secretin can be decreased when used in combination with Oxitropium.Investigational
OxybutyninThe therapeutic efficacy of Human secretin can be decreased when used in combination with Oxybutynin.Approved, Investigational
OxyphenoniumThe therapeutic efficacy of Human secretin can be decreased when used in combination with Oxyphenonium.Approved
PancuroniumThe therapeutic efficacy of Human secretin can be decreased when used in combination with Pancuronium.Approved
ParoxetineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Paroxetine.Approved, Investigational
PentoliniumThe therapeutic efficacy of Human secretin can be decreased when used in combination with Pentolinium.Approved
PhenglutarimideThe therapeutic efficacy of Human secretin can be decreased when used in combination with Phenglutarimide.Experimental
PhenobarbitalThe therapeutic efficacy of Secretin human can be decreased when used in combination with Phenobarbital.Approved, Investigational
PipecuroniumThe therapeutic efficacy of Human secretin can be decreased when used in combination with Pipecuronium.Approved
PirenzepineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Pirenzepine.Approved
ProcyclidineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Procyclidine.Approved
PromethazineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Promethazine.Approved, Investigational
PropanthelineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Propantheline.Approved
PropiverineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Propiverine.Approved, Investigational
QuetiapineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Quetiapine.Approved
QuinidineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Quinidine.Approved, Investigational
ScopolamineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Scopolamine.Approved, Investigational
SolifenacinThe therapeutic efficacy of Human secretin can be decreased when used in combination with Solifenacin.Approved
TiotropiumThe therapeutic efficacy of Human secretin can be decreased when used in combination with Tiotropium.Approved
TolterodineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Tolterodine.Approved, Investigational
TramadolThe therapeutic efficacy of Secretin human can be decreased when used in combination with Tramadol.Approved, Investigational
TrihexyphenidylThe therapeutic efficacy of Human secretin can be decreased when used in combination with Trihexyphenidyl.Approved
TrimebutineThe therapeutic efficacy of Secretin human can be decreased when used in combination with Trimebutine.Approved
TrimethaphanThe therapeutic efficacy of Human secretin can be decreased when used in combination with Trimethaphan.Approved, Investigational
TropatepineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Tropatepine.Experimental
TropicamideThe therapeutic efficacy of Human secretin can be decreased when used in combination with Tropicamide.Approved, Investigational
TrospiumThe therapeutic efficacy of Secretin human can be decreased when used in combination with Trospium.Approved
TubocurarineThe therapeutic efficacy of Human secretin can be decreased when used in combination with Tubocurarine.Approved
UmeclidiniumThe therapeutic efficacy of Human secretin can be decreased when used in combination with Umeclidinium.Approved
VecuroniumThe therapeutic efficacy of Secretin human can be decreased when used in combination with Vecuronium.Approved
Food Interactions
Not Available

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. [PubMed:6168511]
  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. [PubMed:24906040]
  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. [PubMed:25332973]
  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. [PubMed:20944548]
  5. 21-256 Synthetic Human Secretin Pharmacology Review - FDA [Link]
External Links
PubChem Substance
347827873
ChemSpider
17314768
ChEBI
135913
ChEMBL
CHEMBL3039582
ATC Codes
V04CK01 — Secretin
FDA label
Download (98.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Unknown StatusDiagnosticMalignant Neoplasm of Pancreas1
1CompletedDiagnosticPancreatitis, Chronic1
1TerminatedDiagnosticIntraductal Papillary Mucinous Neoplasms1
1TerminatedDiagnosticPancreatitis, Chronic1
1TerminatedDiagnosticPancreatitis, Chronic / Recurrent Acute Pancreatitis1
1, 2CompletedTreatmentPancreatitis, Chronic1
1, 2Enrolling by InvitationDiagnosticHealthy Volunteers / Indigestion1
1, 2RecruitingDiagnosticPancreatitis, Chronic1
1, 2TerminatedDiagnosticMalignant Neoplasm of Pancreas1
2CompletedEducational/Counseling/TrainingObsessive Compulsive Disorder (OCD)1
2CompletedTreatmentSchizophrenic Disorders1
2, 3Active Not RecruitingBasic ScienceBMI >30 kg/m21
3CompletedDiagnosticPancreatic Diseases1
3CompletedDiagnosticPancreatitis1
3CompletedTreatmentAutism, Early Infantile1
3RecruitingTreatmentInjury of Body of Pancreas1
3TerminatedTreatmentAutism, Early Infantile1
4CompletedDiagnosticSphincter of Oddi Dysfunction1
4RecruitingDiagnosticEndoscopic Retrograde Cholangiopancreatography1
Not AvailableCompletedNot AvailableNeoplasms, Pancreatic / Peutz-Jeghers Syndrome (PJS)1
Not AvailableCompletedDiagnosticHealthy Volunteers1
Not AvailableCompletedDiagnosticMalignant Neoplasm of Pancreas1
Not AvailableRecruitingNot AvailableMalignant Neoplasm of Pancreas1
Not AvailableWithdrawnDiagnosticIntraductal Papillary Mucinous Neoplasms / Malignant Neoplasm of Pancreas1
Not AvailableWithdrawnDiagnosticMalignant Neoplasm of Pancreas1
Not AvailableWithdrawnScreeningMalignant Neoplasm of Pancreas1

Pharmacoeconomics

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

Properties

State
Liquid
Experimental Properties
Not Available

Taxonomy

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

Targets

Kind
Protein
Organism
Human
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. [PubMed:21542831]
  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. [PubMed:16192632]

Drug created on November 30, 2015 12:10 / Updated on August 02, 2018 06:18