Mechanism Of Action
The primary action of ChiRhoStim® is to stimulate
pancreatic ductal cells to secrete pancreas fluid in large volumes that contain
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
The pharmacokinetic profile for synthetic human secretin
was evaluated in 12 healthy subjects following a single-dose of human secretin
administered as a 0.4 mcg/kg intravenous bolus. The plasma concentrations of
human secretin declined to baseline concentrations 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 liters.
Stimulation Of Pancreatic Secretions, Including
Bicarbonate To Aid In The Diagnosis Of Exocrine Pancreas Dysfunction
ChiRhoStim® 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 studies, a total of 18 patients with a documented
history of chronic pancreatitis were given 0.2 mcg/kg synthetic human secretin
(sHS), 0.2 mcg/kg synthetic porcine secretin (sPS), and 1 CU/kg (equal to 0.2
mcg/kg for biologically derived secretin (bPS)) in a crossover design. The
results appear in Figures 1 and 2. In another study, 35 healthy subjects were
given sHS at a dose of 0.2 mcg/kg. 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 (greater than 5) to develop
proficiency in proper techniques and to generate normal response ranges for the
commonly assessed parameters for pancreatic exocrine response to ChiRhoStim®.
In three crossover studies evaluating 21 different
patients with a documented history of chronic pancreatitis, sHS was compared to
sPS and bPS at a dose of 0.2 mcg/kg for each drug. All of the patients treated
with these drugs had peak bicarbonate concentrations of less than 80 mEq/L.
Pancreatic secretory response to intravenous synthetic
human secretin in 35 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 greater than or equal to 80
Stimulation Of Gastrin Secretion To Aid In the Diagnosis Of
ChiRhoStim® administered intravenously stimulates gastrin
release in patients with gastrinoma (Zollinger-Ellison Syndrome), whereas no or
only small changes in serum gastrin concentrations occur in healthy subjects
and in patients with duodenal ulcer disease. Discriminant analysis was used to
establish secretin stimulation testing as an aid in the diagnosis of
gastrinoma. An increase from basal levels of greater than or equal to 110 pg/mL
was the optimal point separating positive and negative tests. This gastrin
response is the basis for the use of secretin as a provocative test in the
evaluation of patients in whom gastrinoma is a diagnostic consideration.
In a three way crossover study, 6 patients with tissue
confirmed gastrinoma received synthetic human secretin (ChiRhoStim®), synthetic
porcine secretin and biologically derived porcine secretin at a dose of 0.4
mcg/kg for each drug. Serum gastrin levels were reported to be greater than 110
pg/mL for all secretin products tested after stimulation. Testing of ChiRhoStim®
in 12 healthy subjects demonstrated completely negative results for gastrinoma.
Stimulation Of Pancreatic Secretion To Facilitate
Identification Of The Ampulla Of Vater And The Accessory Papilla During
Endoscopic Retrograde Cholangiopancreatography (ERCP)
In a randomized, placebo controlled crossover study in 24
patients with pancreas divisum undergoing ERCP, ChiRhoStim® 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.
1. Gardner TB, Purich ED and Gordon SR. Pancreatic Duct
CompliaNovel Endoscopic Ultrasound Diagnostic Tool for ChronicMar;41(2):290-94.
2. Jorpes, E. and Mutt V. On the biological assay of
secretin. The Scand. 1966 Mar;66(3):316-25.