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| Primary information |
|---|
| ID | 13150 |
| Therapeutic ID | Th1387 |
| Protein Name | Secretin human |
| Sequence | >Th1387_Secretin_human
HSDGTFTSELSRLREGARLQRLLQGLV
|
| Molecular Weight | 3039.44 |
| Chemical Formula | C130H220N44O39 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The elimination half life of synthetic human secretin is 45 minutes [FDA Label]. |
| 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 [L1875]. 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 [A32276] 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 [A32275]. 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 [FDA Label] that supports a-helical formation [A32275]. The carboxyl-terminal amino acid, valine, is amidated. Synthetic human secretin displays equivalent biological activity and properties as naturally-occurring secretin [A32265]. 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). |
| Indication/Disease | Indicated for the stimulation of: - pancreatic secretions, including bicarbonate, to aid in the diagnosis of pancreatic exocrine dysfunction [FDA Label]. - gastrin secretion to aid in the diagnosis of gastrinoma [FDA Label]. - pancreatic secretions to facilitate the identification of the ampulla of Vater and accessory papilla during endoscopic retrograde cholangiopancreatography (ERCP) [FDA Label]. |
| 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 [FDA 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 [FDA 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 [FDA 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 [FDA 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 [A32267]. |
| 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 [FDA 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 [L1875]. Bicarbonate ions are released into the duodenum from the centroacinar cells, and epithelia lining the pancreatic and biliary ducts [A32275]. Human secretin is a ligand at G-protein coupled secretin receptors which are expressed in the basolateral domain of several tissue cell types [A32275], including pancreas, stomach, liver, colon and other tissues [FDA 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) [A32275]. Activation of CFTR activates Cl-/HCO3- anion exchanger 2 and leads to secretion of bicarbonate-rich-pancreatic fluid [A32275]. Via the same cAMP signalling pathway, secretin promotes the secretion of water and electrolytes in cholangiocytes [A32275]. 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 [FDA Label]. Additionally, secretin acts as a diuretic to increase urinary volume and bicarbonate excretion [A32275, A32276]. |
| 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 [L1875]. Studies assessing the carcinogenic potential, mutagenicity, or potential for impairment of fertility have not been conducted with synthetic human secretin [FDA Label]. |
| Metabolism | NA |
| 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 [FDA Label]. |
| The volume of distribution is 2.7 L [FDA Label]. |
| Clearance | The clearance of synthetic human secretin is 580.9 ± 51.3 mL/min [FDA Label]. |
| Categories | Hormones, Hormone Substitutes, and Hormone Antagonists |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Secretin receptor |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | (4S)-5-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[2-[[(2S)-1-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-4-carboxybutanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoic acid |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |