"VANCOUVER, British Columbia â€” There is a small but statistically significant increased risk for acute pancreatitis among the dipeptidyl peptidase-4 (DPP-4) inhibitor class of glucose-lowering agents used in type 2 diabetes treatment, a new meta-a"...
The primary action of ChiRhoStim® (human secretin) is to increase the volume and bicarbonate content of secreted pancreatic juices. The standard unit of activity used for ChiRhoStim® (human secretin) is the clinical unit as defined in the literature.(5) Synthetic human secretin (sHS), synthetic porcine secretin (sPS) and biologically derived porcine secretin (bPS) have been evaluated and compared in the validated cat bioassay used for release of bPS. sHS and sPS were found to have similar pharmacological activity in terms of stimulating the exocrine pancreas to secrete juice and bicarbonate. The potency correlation with bPS for both sHS and sPS was 0.2 mcg (sHS or sPS) corresponding to 1 CU (bPS). The biological activity of sHS and sPS was approximately 5.0 CU per mcg as opposed to 3.0 CU per mcg for bPS.
Mechanism of Action
Secretin is a hormone that is normally released from the duodenum upon exposure of the proximal intestinal lumen to gastric acid, fatty acids and amino acids. Secretin is released from enterochromaffin cells in the intestinal mucosa. Secretin receptors have been identified in the pancreas, stomach, liver, colon and other tissues. When secretin binds to secretin receptors on pancreatic duct cells it opens cystic fibrosis transmembrane conductance regulator (CFTR) channels, leading to secretion of bicarbonate-rich-pancreatic fluid. Secretin may also work through vagal-vagal neural pathways since stimulation of the efferent vagus nerve stimulates bicarbonate secretion and atropine blocks secretin-stimulated pancreatic secretion. See references 6 and 7 for additional details on mechanism of action of secretin and feedback controls.
The PK profile for synthetic human secretin was evaluated in 12 normal subjects. After intravenous bolus administration of 0.4 mcg/kg, synthetic human secretin concentration rapidly declines to baseline secretin levels within 90 to 120 minutes. The elimination half-life of synthetic human secretin is 45 minutes. The clearance of synthetic human secretin is 580.9 ± 51.3 mL/min and the volume of distribution is 2.7 L.
Animal Toxicology and/or Pharmacology
A single intravenous dose of synthetic human secretin at 20 mcg/kg was not lethal to mice or rabbits.
Stimulation of pancreatic secretions, including bicarbonate to aid in the diagnosis of Exocrine Pancreas Dysfunction:
ChiRhoStim® (human secretin) administered intravenously stimulates the exocrine pancreas to secrete pancreatic juice, which can assist in the diagnosis of exocrine pancreas dysfunction. Normal ranges for pancreatic secretory response to intravenous secretin in patients with defined pancreatic disease have been shown to vary. One source of variation is related to the inter-investigator differences in operative technique.
In two crossover studies (CRC98-2 and CRC99-9), a total of 18 patients with a documented history of chronic pancreatitis were given sHS, sPS and bPS. The results appear in Figures 1 and 2. In another study, 35 normal volunteers were given sHS. The results appear in Figures 1 and 2.
The values obtained for Figures 1 and 2 were performed by investigators skilled in performing secretin stimulation testing and are to be taken only as guidelines. These results should not be generalized to results of secretin stimulation testing conducted in other laboratories. However, a volume response of less than 2 mL/kg/hr, bicarbonate concentration of less than 80 mEq/L, and a bicarbonate output of less than 0.2 mEq/kg/hr are consistent with impaired pancreatic function.
A physician or institution planning to perform secretin stimulation testing as an aid to the diagnosis of pancreatic disease should begin by assessing enough normal subjects (> 5) to develop proficiency in proper techniques and to generate normal response ranges for the commonly assessed parameters for pancreatic exocrine response to ChiRhoStim® (human secretin) .
In three crossover studies (CRC 98-1, CRC 98-2, and CRC 99-9) evaluating 21 different patients with a documented history of chronic pancreatitis, synthetic human secretin (sHS) was compared to synthetic porcine secretin (sPS) and biologically derived secretin (bPS). All of the patients treated with these drugs had peak bicarbonate concentrations of < 80 mEq/L.
Pancreatic secretory response to intravenous synthetic human secretin in 35 normal healthy subjects demonstrated a mean peak bicarbonate concentration of 100 mEq/L and a mean total volume over one hour of 260.7 mL. All 35 subjects had peak bicarbonate concentrations ≥ 80 mEq/L.
Stimulation of gastrin secretion to aid in the diagnosis of gastrinoma
ChiRhoStim® (human secretin) administered intravenously stimulates gastrin release in patients with gastrinoma (Zollinger-Ellison Syndrome), whereas no or only small changes in serum gastrin concentrations occur in normal subjects and in patients with duodenal ulcer disease. Deveney, et al. established the high sensitivity and specificity of the secretin stimulation test to aid in the diagnosis of gastrinoma and found using discriminant analysis that an increase from baseline of ≥ 110 pg/mL was the optimal point separating positive and negative tests.(8) This gastrin response is the basis for the use of synthetic human secretin as a provocative test in the evaluation of patients in whom gastrinoma is a diagnostic consideration.
In a three way crossover study of 6 patients with tissue diagnosed gastrinoma, there was agreement among synthetic human secretin (ChiRhoStim® (human secretin) ), synthetic porcine secretin and biologically derived porcine secretin regarding gastrin levels. Serum gastrin levels were reported to be > 110 pg/mL for all secretin products tested after stimulation with 0.4 mcg/kg secretin. Testing of ChiRhoStim® (human secretin) in 12 healthy volunteers demonstrated completely negative results for gastrinoma.
Facilitation of identification of the ampulla of Vater and the accessory papilla during endoscopic retrograde cholangiopancreatography (ERCP) to assist in cannulation of the pancreatic ducts
In a randomized, placebo controlled crossover study in 24 patients with pancreas divisum undergoing ERCP, synthetic human secretin administration at a dose of 0.2 mcg/kg resulted in 16 of 24 successful cannulations of the minor duct compared to 2 of 24 for placebo.
5. Jorpes, E. and Mutt V. On the biological assay of secretin. The reference standard. Acta Physiol Scand. 1966 Mar;66(3):316-25.
6. Chey WY, Chang T-M, Secretin. In: Kasin AJ. Editor. Handbook of Biologically Active Peptides. Elsevier, Amsterdam. 2006;1115-1122.
7. Whitcomb DC. Neurohormonal Control of the Exocrine Pancreas. In:Greeley JR G, editor. Endocrinology of the Gastrointestinal System. Totowa NJ:Humana Press. 1998;239-258.
8. Deveney, C.W., et al. Use of Calcium and Secretin in the Diagnosis of Gastrinoma (Zollinger-Ellison Syndrome). Ann Intern Med. 1977 Dec;87(6):680-6.
Last reviewed on RxList: 7/17/2007
This monograph has been modified to include the generic and brand name in many instances.
Additional ChiRhoStim Information
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