Effect of a new oral somatostatin analog (SDZ CO 611) on gastric emptying, mouth to cecum transit time, and pancreatic and gut hormone release in normal male subjects.

Abstract

Sixteen healthy male volunteers participated in a randomized, double blind, parallel groups study. Subjects received either 1 or 5 mg SDZ CO 611 (a new, orally active somatostatin analog) twice daily over a 14-day period and acted as their own controls. Gastric emptying of 99mTc and mouth to cecum transit time, as measured by the breath hydrogen technique, after a mixed meal containing lactulose and 99mTc-diethylenetriaminepentaacetate, were assessed once before, twice during, and once after the period of study medication. Gastric emptying of 99mTc was significantly accelerated by the higher dose of SDZ CO 611, whereas mouth to cecum transit time was prolonged by the drug in a dose-dependent manner. Both doses of SDZ CO 611 led to suppression of the fasting level and postprandial release of several gastrointestinal and pancreatic hormones. This effect was more marked in those subjects taking 10 mg/day of the study medication. Motilin and pancreatic polypeptide were the most sensitive to the inhibitory actions of the analog. Glucose tolerance was significantly impaired by the 10-mg dose of the drug. We conclude that this new, orally active derivative of somatostatin is as effective on the gastrointestinal tract as the sc somatostatin analog octreotide. It would, therefore, be a useful advance in the treatment of gastroenteropancreatic tumors.

Dumping syndrome after esophageal, gastric or bariatric surgery: pathophysiology, diagnosis, and management

“…Somatostatin analogues are an effective treatment option for patients with well‐established dumping syndrome who fail to respond to and/or do not tolerate initial dietary modification and acarbose treatment. Somatostatin analogues target various steps in the pathophysiology of dumping syndrome, including delaying gastric emptying, delaying transit through the small intestine, inhibiting the release of GI hormones, inhibiting insulin secretion and inhibiting postprandial vasodilation . Somatostatin inhibition of GLP‐1 secretion is mediated via activation of the somatostatin receptor subtype (sst) 5, with a lesser effect through sst2 .…”

The helix-loop-helix transcription factor SEF-2 regulates the activity of a novel initiator element in the promoter of the human somatostatin receptor II gene.

“…A series of studies employing Northern blot, RT-PCR and in situ hybridization analysis has revealed complex gene typespecific expression patterns in many regions of the central nervous system (CNS) and peripheral tissues. The areas of intensive somatostatin receptor expression include the hypothalamic-hypophyseal system, which regulates the adenohypophyseal release of GH, TSH and prolactin (Brazeau et al, 1972), the widespread somatostatinergic system in the CNS modulating many cognitive and vegetative functions and references therein) and the gastroenteropancreatic system of neuroendocrine cells that regulates gastric acid and gastroenteropancreatic hormone release (Nelson-Piercy et al, 1994). Furthermore, a recent study revealed temporally and spatially regulated expression patterns of SSTR2 and SSTR4 during embryonic development of the brain.…”

The effect of octreotide on gastric emptying at a dosage used to prevent complications after pancreatic surgery: a randomised, placebo controlled study in volunteers

“…Other actions on gastrointestinal motility are the inhibition of antral motility, the induction of phase III like activity of the migrating motor complexes in the interdigestive state, and prolongation of the mouth to caecum transit time (MCTT) 2223 25 26 These studies, which addressed the effect of octreotide on gastric emptying, tested the effect of a single low dose (50 μg) subcutaneously, or oral doses of octreotide 2223 In an experimental study of the effect of octreotide on postoperative ileus in dogs, Cullen et al found a delay in gastric emptying for a dosage scheme of 0.83 μg/kg/h in continuous subcutaneous infusion 27.…”