Octreotide

Chemical properties

Colourless to off-white lyophilised solid

Originator

Sandostatin,Novartis Pharma AG,Switz.

The Uses of Octreotide

Octapeptide analog of Somatostatin. A gastric antisecretory agent. Used in treatment of acromegaly

The Uses of Octreotide

natural hormone somatostatin

The Uses of Octreotide

Octreotide acetate USP (Sandostatin) is used to treat Mestastatic carcinoid tumors; vasoactive intestinal peptide-secretory tumors.

What are the applications of Application

Octreotide Acetate is an octapeptide analog of Somatostatin

Indications

Octreotide (Sandostatin) is a synthetic somatostatin analogue. It is used in a variety of situations and must be given subcutaneously or intravenously. Most commonly, it is used as a continuous intravenous infusion in patients hospitalized with bleeding varices, because it decreases splanchnic circulation and therefore reduces portal pressures.A long-acting depot form is approved for the suppression of severe diarrhea and flushing associated with malignant carcinoid syndrome and for the treatment of the profuse watery diarrhea associated with vasoactive intestinal peptide tumor.

Indications

Octreotide is useful in inhibiting the secretion of various autacoids and peptide hormones by metastatic carcinoid tumors (serotonin) and islet cell carcinomas of the pancreas (gastrin, glucagon, insulin, vasoactive intestinal peptide). The diarrhea and flushing associated with the carcinoid syndrome are improved in 70 to 80% of the patients treated with octreotide. Its side effects, which are usually mild, include nausea and pain at the injection site. Mild transient hypoglycemia or hyperglycemia may result from alterations in insulin, glucagon, or growth hormone secretion.

Manufacturing Process

Synthesis of octreotide and derivative thereof can be carried out by two methods. The first method is synthesized initially by fragment condensation solution phase procedures. The synthetic process of octreotide has been described by Bauer et al. (1). The second method is the synthese by solidphase procedures. Edward et al. (2) isolated side chain protected octreotide with a total yield of 14% by cleaving the protected peptide from the resin with threoninol. Arano et al. (3) carried out another solid phase method for octreotide. and produced it in overall 31.8% yield based on the starting FmocThr(tBu)-ol-resin. The basic difference from the other procedures already described is that the introduction of the threoninol is carried out upon the protected peptidic structure (resin-free), which, when appropriately activated, leads quantitatively and without needing to make temporary protections upon the threoninol, to the protected precursor of octreotide, which in turn, with a simple acid treatment leads to octreotide with very high yields.
At first the Fmoc-Cys-Cl-trityl-resin was prepared. The incorporation of the Fmoc-Cys(trt)-OH residue upon 2Cl-Trt resin is accomplished with an excess of 1 eq. of Fmoc-Cys(Trt) and 2.5 eq. of N,N'-diisopropylethylamine (DIEA).
2.93 g (5.0 mmol) of Fmoc-Cys(Trt) are incorporated upon 5 g of resin (f = 1.28 mmol/g of resin, 6.4 mmol). The resin and the amino acid are weighed in separate containers and left to dry in a vacuum with KOH, for a minimum of two hours. A 1/1 solution of DIEA and CH2Cl2 (DCM) (dry on a 4A sieve) is prepared. The already dry amino acid is dissolved with dry DCM at a concentration of 0.1 g of resin per ml, adding the minimum quantity of dry DMF to complete the dissolution. 1/3 of the 1.8 ml (12.5 mmol) DIEA solution is added to this transparent solution in 1.8 ml of DCM. This is thoroughly homogenized and added to the dry resin. It is subjected to vigorous magnetic agitation for five minutes and the rest of the DIEA is added to the reaction; the mixture is allowed to react for forty minutes more. Then, 4 ml of dry MeOH are added and allowed to react for 10 minutes, after which the resin is filtered and the washings described below are carried out.

brand name

Sandostatin (Novartis).

Therapeutic Function

Antiulcer, Growth hormone inhibitor

General Description

Pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards

Clinical Use

Relief of symptoms of gastro-enteropancreatic endocrine tumours and acromegaly

Safety Profile

A poison by subcutaneous andintravenous routes. Human systemic effects: changes instructure or function of endocrine pancreas, liver functiontests impaired. When heated to decomposition it emitstoxic vapors of NOx and SOx

Drug interactions

Potentially hazardous interactions with other drugs
Ciclosporin: ciclosporin concentration reduced.

Metabolism

Extensive hepatic metabolism.1