Octreotide - How It Works
Clinical pharmacology details from the US FDA-approved label: how Octreotide works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Octreotide acetate injection exerts pharmacologic actions similar to the natural hormone, somatostatin. It is an even more potent inhibitor of GH, glucagon, and insulin than somatostatin. Like somatostatin, it also suppresses luteinizing hormone (LH) response to gonadotropin releasing hormone (GnRH), decreases splanchnic blood flow, and inhibits release of serotonin, gastrin, VIP, secretin, motilin, and pancreatic polypeptide. By virtue of these pharmacological actions, octreotide has been used to treat the symptoms associated with metastatic carcinoid tumors (flushing and diarrhea), and VIP secreting adenomas (watery diarrhea).
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Octreotide acetate injection exerts pharmacologic actions similar to the natural hormone, somatostatin.
It is an even more potent inhibitor of GH, glucagon, and insulin than somatostatin.
Like somatostatin, it also suppresses luteinizing hormone (LH) response to gonadotropin releasing hormone (GnRH), decreases splanchnic blood flow, and inhibits release of serotonin, gastrin, VIP, secretin, motilin, and pancreatic polypeptide.
By virtue of these pharmacological actions, octreotide has been used to treat the symptoms associated with metastatic carcinoid tumors (flushing and diarrhea), and VIP secreting adenomas (watery diarrhea).
12.2 Pharmacodynamics Octreotide substantially reduces GH and/or IGF-1 (somatomedin C) levels in patients with acromegaly.
Single doses of octreotide have been shown to inhibit gallbladder contractility and to decrease bile secretion in normal volunteers.
In controlled clinical trials, the incidence of gallstone or biliary sludge formation was markedly increased [see Warnings and Precautions ] .
Octreotide suppresses secretion of TSH.
12.3 Pharmacokinetics Absorption After subcutaneous injection, octreotide is absorbed rapidly and completely from the injection site.
Peak concentrations of 5.2 ng/mL (100-mcg dose) were reached 0.4 hours after dosing.
Using a specific radioimmunoassay, IV and subcutaneous doses were found to be bioequivalent.
Peak concentrations and area under the curve (AUC) values were dose proportional after IV single doses up to 200 mcg and subcutaneous single doses up to 500 mcg and after subcutaneous multiple doses up to 500 mcg 3 times a day (1,500 mcg/day).
In patients with acromegaly, a mean peak concentration of 2.8 ng/mL (100-mcg dose) was reached in 0.7 hours after subcutaneous dosing.
Distribution In healthy volunteers, the distribution of octreotide from plasma was rapid (tα½ = 0.2 h), the volume of distribution (V dss ) was estimated to be 13.6 L, and the total body clearance ranged from 7 L/hr to 10 L/hr.
In blood, the distribution into the erythrocytes was found to be negligible and about 65% was bound in the plasma in a concentration-independent manner.
Binding was mainly to lipoprotein and, to a lesser extent, to albumin.
In patients with acromegaly, the volume of distribution (V dss ) was estimated to be 21.6 ± 8.5 L, and the total body clearance was increased to 18 L/h.
The mean percent of the drug bound was 41.2%.
Elimination The elimination of octreotide from plasma had an apparent half-life of 1.7 to 1.9 hours compared with 1 to 3 minutes with the natural hormone.
The duration of action of octreotide acetate injection is variable but extends up to 12 hours depending upon the type of tumor.
Pharmacokinetics
12.3 Pharmacokinetics Absorption After subcutaneous injection, octreotide is absorbed rapidly and completely from the injection site. Peak concentrations of 5.2 ng/mL (100-mcg dose) were reached 0.4 hours after dosing. Using a specific radioimmunoassay, IV and subcutaneous doses were found to be bioequivalent. Peak concentrations and area under the curve (AUC) values were dose proportional after IV single doses up to 200 mcg and subcutaneous single doses up to 500 mcg and after subcutaneous multiple doses up to 500 mcg 3 times a day (1,500 mcg/day). In patients with acromegaly, a mean peak concentration of 2.8 ng/mL (100-mcg dose) was reached in 0.7 hours after subcutaneous dosing. Distribution In healthy volunteers, the distribution of octreotide from plasma was rapid (tα½ = 0.2 h), the volume of distribution (V dss ) was estimated to be 13.6 L, and the total body clearance ranged from 7 L/hr to 10 L/hr. In blood, the distribution into the erythrocytes was found to be negligible and about 65% was bound in the plasma in a concentration-independent manner. Binding was mainly to lipoprotein and, to a lesser extent, to albumin. In patients with acromegaly, the volume of distribution (V dss ) was estimated to be 21.6 ± 8.5 L, and the total body clearance was increased to 18 L/h. The mean percent of the drug bound was 41.2%. Elimination The elimination of octreotide from plasma had an apparent half-life of 1.7 to 1.9 hours compared with 1 to 3 minutes with the natural hormone. The