Somatostatin and somatostatin analogues: pharmacokinetics and pharmacodynamic effects

Somatostatin is a 14 amino acid peptide that inhibits pancreatic exocrine and endocrine secretion. Its clinical application has been limited by its very short half life, necessitating continuous intravenous infusion. Octreotide is an 8 amino acid synthetic analogue of somatostatin that possesses similar pharmacological effects. It has a much longer duration of action, however, and can be given subcutaneously. Both the intravenous and subcutaneous routes of injection of octreotide are well tolerated. Peak serum concentrations occur within 30 minutes after subcutaneous administration and within four minutes of a three minute intravenous infusion. Serum concentration increases linearly with dose. Octreotide is distributed rapidly, mainly in the plasma, where it is 65% protein bound. The elimination half life is about 1.5 hours and about 32% of a subcutaneous dose is excreted in the urine as unchanged octreotide. Octreotide inhibits gastroenteropancreatic secretion, especially of insulin, glucagon, pancreatic polypeptide, gastric inhibitory polypeptide, and gastrin. It also inhibits both release of thyroid stimulating hormone and growth hormone secretion in response to exercise, insulin induced hypoglycaemia, and argenine stimulation. Octreotide reduces splanchnic blood flow in healthy volunteers and hepatic venous pressure in cirrhotic patients. It can accelerate or delay gastric emptying, prolong transit time at moderate to high doses, stimulate motility at low doses, and inhibit gall bladder emptying. Octreotide considerably inhibits pentagastrin stimulated gastric acid secretion and significantly diminishes exocrine pancreatic function (amylase, trypsin, lipase). Octreotide increases intestinal transit time and decreases endogenous fluid secretion in the jejunum and ileum, thus increasing the absorption of water and electrolytes. These pharmacological effects of the analogue point to its therapeutic role in a variety of endocrine and gastrointestinal disorders.