Octreotide
Octreotide is a synthetic somatostatin analog used to treat acromegaly, neuroendocrine tumors, and variceal bleeding, with a half-life 30x longer than native somatostatin.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C49H66N10O10S2 |
| Molecular Weight | 1019.24 g/mol |
| CAS Number | 83150-76-9 |
| IUPAC Name | D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol |
| Peptide Class | Somatostatin Analog |
| Sequence Homology | Modified cyclic octapeptide |
Structure
Octreotide is a synthetic cyclic octapeptide that mimics the pharmacologically active tetrapeptide sequence (Phe-Trp-Lys-Thr) of native somatostatin. The disulfide bridge between the two cysteine residues creates a conformationally constrained ring. D-phenylalanine and D-tryptypophan residues confer resistance to proteolytic degradation, extending the half-life from 2 minutes (somatostatin) to approximately 2 hours.
Mechanism of Action
Octreotide binds with high affinity to somatostatin receptor subtypes SST2 and SST5, inhibiting the release of growth hormone, thyroid-stimulating hormone, insulin, glucagon, and various gastrointestinal peptides. It reduces splanchnic blood flow and suppresses secretory activity of the gastrointestinal tract.
Clinical Applications
Octreotide (Sandostatin) is approved for:
- Acromegaly: First-line medical therapy to normalize GH and IGF-1 levels
- Neuroendocrine tumors: Symptomatic control of carcinoid syndrome and VIPomas
- Variceal bleeding: Reduces portal pressure in acute esophageal variceal hemorrhage
- Short bowel syndrome: Reduces diarrhea and fluid requirements
A long-acting release (LAR) formulation (Sandostatin LAR) allows monthly intramuscular injection.
Pharmacokinetics
- Half-life: 1.7-1.9 hours (subcutaneous); 2 hours (intravenous)
- Tmax: Subcutaneous 0.4-1 hour
- Bioavailability: 60-63% after subcutaneous injection
- Metabolism: Hepatic and renal degradation
- LAR formulation: Sustained release over 28 days from PLG microspheres
Safety and Side Effects
Common adverse effects include gastrointestinal disturbances (diarrhea, nausea, abdominal pain, steatorrhea), hyperglycemia or hypoglycemia, and cholelithiasis (15-30% with long-term use). Injection site reactions occur with subcutaneous administration. Cardiac conduction abnormalities have been reported rarely.
References
- Lamberts, S.W., et al. (1985). The effects of the somatostatin analog SMS 201-995 on normal pituitary function. New England Journal of Medicine, 313, 1576-1580.
- Colao, A., et al. (2006). Octreotide LAR vs lanreotide SR in acromegaly. Journal of Clinical Endocrinology & Metabolism, 91, 3062-3069.
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