Octreotide acetate

Octreotide acetate (Sandostatin) is an octapeptide congener of native somatostatin, inhibits the secretion of insulin and glucagon. It reduces production of IGF-1 and IGF-2 by the liver by modulation of growth-hormone secretion from the pituitary gland. [1]
The insulin-like growth factors IGF-1 and IGF-2, endogenously produced polypeptide hormones and potent stimulators of cell proliferation, are under investigation as clinical targets in prostate cancer.
Octreotide acetate decreased the urinary excretion of uric acid as well as the plasma concentrations of glucagon and insulin. Octreotide acetate decreased the urinary excretion of sodium and chloride without significiant influence on creatinine clearance, while the concentrations of lactic acid, pyruvic acid in blood, and cyclic AMP in plasma were not changed. [1]
References:
[1] Tetsuya yamamoto, Yuji moriwaki et al. Effect of Octreotide acetate on the Plasma Concentration and Urinary Excretion of Uridine and Purine Bases. Endocrine Journal 2002, 49(2),139-144.

[The Use of Octreotide Acetate in the Management of Refractory Chylothorax Following Surgical Treatment for Lung Cancer].[Pubmed:27246125]

Kyobu Geka. 2016 Jun;69(6):429-32.

A 78-year-old man underwent right upper lobectomy with systemic lymph node dissection for lung cancer. On the 1st operative day, chylothorax was suspected by a large amount of yellowish-white fluid through the chest tubes. In spite of stopping the oral intake as a conservative therapy, a lot of chylous drainage was continued, and we chose surgical treatment at day 7 after operation, however, chylous discharge did not decrease significantly. Finally we decided to try octreotide administration subcutaneously. After continuous subcutaneous infusion of octreotide, the amount of chylous discharge was reduced dramatically. Then we have done 2 times of pleurodesis with OK-432. The chest tubes were removed at day 17 after the 2nd operation, and the chylothorax was improved. It was suggested that octreotide administration was a highly effective therapy against postoperative refractory chylothorax.

Treatment of Gastrin-Secreting Tumor With Sustained-Release Octreotide Acetate in a Dog.[Pubmed:26535461]

J Am Anim Hosp Assoc. 2015 Nov-Dec;51(6):407-12.

An 8 yr old, intact male Shiba Inu was presented with loose stool, polydipsia, hematuria, vomiting, and anorexia. On abdominal ultrasonography, numerous nodules were detected in the hepatic parenchyma distributed diffusely throughout all lobes. Excisional biopsy of one of the nodules was performed via exploratory laparotomy. A histopathological diagnosis of the lesion was carcinoid, and the tumor cells stained positive to chromogranin A and gastrin. The serum gastrin level of the dog was 45,613 pg/mL (reference range: 160-284). In addition to medical treatment with omeprazole(c) and famotidine(e), suppression of gastrin secretion was attempted with Octreotide acetate. A test dose of Octreotide acetate significantly decreased the serum gastrin level to approximately one third of the baseline in 2 hr and the effect lasted approximately for 6 hr. On day 21, treatment with sustained-release formulation of Octreotide acetate(a) (5 mg intramuscular, q 4 wk) was initiated. The serum gastrin concentration gradually decreased over 32 days and then progressively increased in parallel with the progression of the hepatic nodules. The dog gradually developed recurrence of initial clinical signs, and was lost to follow-up on day 510.

A rapid hydrolysis method and DABS-Cl derivatization for complete amino acid analysis of octreotide acetate by reversed phase HPLC.[Pubmed:26002809]

Amino Acids. 2015 Nov;47(11):2255-63.

Octreotide as a synthetic cyclic octapeptide is a somatostatin analog with longer half-life and more selectivity for inhibition of the growth hormone. The acetate salt of octreotide is currently used for medical treatment of somatostatin-related disorders such as endocrine and carcinoid tumors, acromegaly, and gigantism. Octreotide contains both cysteine and tryptophan residues which make the hydrolysis part of its amino acid analysis procedure very challenging. The current paper introduces a fast and additive-free method which preserves tryptophan and cysteine residues during the hydrolysis. Using only 6 M HCl, this hydrolysis process is completed in 30 min at 150 degrees C. This fast hydrolysis method followed by pre-column derivatization of the released amino acids with 4-N,N-dimethylaminoazobenzene-4'-sulfonyl chloride (DABS-Cl) which takes only 20 min, makes it possible to do the complete amino acid analysis of an octreotide sample in a few hours. The highly stable-colored DABS-Cl derivatives can be detected in 436 nm in a reversed phase chromatographic system, which eliminates spectral interferences to a great extent. The amino acid analysis of Octreotide acetate including hydrolysis, derivatization, and reversed phase HPLC determination was validated according to International Conference of Harmonization (ICH) guidelines.

Stability of octreotide acetate decreases in a sodium bisulfate concentration-dependent manner: compatibility study with morphine and metoclopramide injections.[Pubmed:25984298]

Eur J Hosp Pharm Sci Pract. 2015 May;22(3):171-175.

PURPOSE: Sodium bisulfate is known to affect the stability of octreotide. However, the critical concentration of sodium bisulfate is not known. Therefore, we assessed the critical concentration of sodium bisulfate needed to preserve the stability of octreotide using actual drugs containing sodium bisulfate. METHODS: Although morphine and metoclopramide preparations are considered to be compatible with octreotide, some of their products are known to contain sodium bisulfate. Thus, octreotide was mixed with preparations of sodium bisulfate solutions at serial concentrations and morphine and metoclopramide preparations containing sodium bisulfate, and octreotide stability was then evaluated using high performance liquid chromatography. RESULTS: Octreotide concentrations decreased significantly at a sodium bisulfate concentration of 0.1 mg/mL or higher after 10 days when octreotide was mixed with sodium bisulfate solutions at various concentrations. A significant decrease in octreotide concentrations also occurred when it was mixed with morphine and metoclopramide preparations containing sodium bisulfate and stored for 10 days; however, slight decreases were observed in the mixture with both preparations and were within the clinically acceptable range for morphine preparations. CONCLUSIONS: These results indicate that the residual rate of octreotide decreases with time in a sodium bisulfate concentration-dependent manner when octreotide was mixed with morphine or metoclopramide. However, this incompatibility may be clinically acceptable when the final sodium bisulfate concentration is lower than 0.1 mg/mL and the mixed solution is used within 7 days.

Molecular pharmacology of somatostatin receptors.[Pubmed:7870182]

Naunyn Schmiedebergs Arch Pharmacol. 1994 Nov;350(5):441-53.

The neuropeptide somatostatin (SRIF) is widely expressed in the brain and in the periphery in two main forms, SRIF-14 and SRIF-28. Similarly, the presence of SRIF receptors throughout the whole body has been reported. SRIF produces a variety of effects including modulation of hormone release (e.g. GH, glucagon, insulin), of neurotransmitter release (e.g. acetylcholine, dopamine, 5-HT), and its own release is modulated by many neurotransmitters. SRIF affects cognitive and behavioural processes, the endocrine system, the gastrointestinal tract and the cardiovascular system and also has tumor growth inhibiting effects. Initially, two classes of SRIF receptors have been proposed on the basis of biochemical and functional studies. However, the recent cloning of five putative SRIF receptor subtypes which belong to the G-protein coupled receptor superfamily suggests that SRIF mediates its various effects via a whole family of receptors. Here we review, in this new context, the molecular pharmacology of the SRIF receptor subtypes present in the brain and in the periphery, and address the question of nomenclature of SRIF receptors.

Cloned somatostatin receptors: identification of subtype-selective peptides and demonstration of high affinity binding of linear peptides.[Pubmed:8100350]

Mol Pharmacol. 1993 Jun;43(6):838-44.

The recent molecular cloning of the genes encoding three somatostatin (SRIF) receptor subtypes has allowed for the individual expression of these receptors in mammalian cells and characterization of their respective pharmacological profiles. In the present study, we have investigated the affinities of a battery of SRIF analogues to bind to SRIF receptor subtypes SSTR1 (cloned somatostatin complex), SSTR2, and SSTR3, as well as their abilities to inhibit the release of growth hormone from anterior pituitary cells in vitro. We labeled SSTR1 and SSTR3 receptors expressed in Chinese hamster ovary and COS-1 cells, respectively, with the metabolically stable SRIF analogue 125I-CGP 23996. SSTR2 receptors expressed in Chinese hamster ovary cells were labeled with the SSTR2-specific radioligand 125I-MK-678. Inhibition studies were performed using SRIF analogues of differing structures, including hexapeptide analogues similar to MK-678, octapeptide analogues similar to SMS 201-995, pentapeptide analogues similar to c[Ahep-Phe-D-Trp-Lys-Thr(Bzl)] (SA), and linear SRIF analogues. SSTR1 bound SRIF and SRIF-28 with high affinity and the peptide SA and its structural analogues with low affinity. The hexapeptides did not interact with SSTR1 at concentrations as high as 1 microM, and only a few of the octapeptides or linear peptides bound, with very low affinities. In contrast, 125I-MK-678 binding to SSTR2 was potently inhibited by the hexapeptides, octapeptides, and some of the linear compounds, whereas SA and its analogues did not bind to SSTR2. The potencies of the various SRIF agonists to inhibit growth hormone release in vitro was highly correlated with their potencies to inhibit radioligand binding to SSTR2, but not to SSTR1 or SSTR3. SSTR3 bound analogues of each class but with moderate to low affinities, with the exception of several linear peptides and one of the octapeptides. We report for the first time the binding affinities of linear analogues of SRIF, some of which display subnanomolar affinities and are highly selective for SRIF receptor subtypes. Most importantly, these studies identify several peptide analogues that are highly potent, specific, and selective for individual subtypes of SRIF receptors. Such information, coupled with the knowledge of the distribution of these receptor subtypes in normal and pathological tissues, will be critical for more specific experimental and therapeutic interventions.

Octreotide is a somatostatin analog that binds to the somatostatin receptor, mainly subtypes 2, 3, and 5, increases Gi activity, and reduces intracellular cAMP production.

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