• Journal of Yeungnam Medical Science
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• v.10 no.1
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• pp.144-156
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• 1993

This study was performed to investigate the effect of octreotide on the contractility of rat vas deferens. The smooth muscle strips isolated from the prostatic portion were myographied in isolated organ bath, Electric field stimulation (monophasic square wave, duration: 1 mSec, voltage : 50 V, frequency : 5 Hz or 30 Hz, train: 10 Sec) produced reproducible contraction. The contraction was composed of two component, first phasic component (FPC) and second tonic component (STC). These contractions were abolished by tetrodotoxin ($1{\mu}M$). Octreotide inhibited the field stimulation induced contractions both FPC and STC concentration-dependently. The FPC was decreased by a desentization of purinergic receptor by pretreatment of mATP, and the STC was decreased by pretreatment of reserpine(3 mg/kg, IP) 24 hours before experiments. Octreotide reduced the field stimulation induced contraction in the presence of mATP and of reserpinized muscle strips. The inhibitory effect of octreotide was more potent at 5 Hz than at 30 Hz. Octreotide did not affect basal ton and exogenous norepinephrine- or ATP-induced contraction. These results suggest that octreotide inhibit the contractility of the isolated rat vas deferens by inhibition of the release of neurotransmitters, both ATP and norepinephrine from adrenergic nerve terminal.

• Journal of Pharmaceutical Investigation
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• v.41 no.2
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• pp.91-94
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• 2011

The purpose of this study was to investigate the effect of peptide charge on the interaction between peptide and poly(D,L-lactide-co-glycolide) (PLGA) for evaluating mechanism of acylated peptide formation in PLGA matrix. As a model peptide, octreotide, a synthetic somatostatin analogue and active ingredient of commercial PLGA product, was used. The disulfide group of octreotide was reduced with dithiothreitol and the sulfhydryl groups were modified with N-${\beta}$-maleimidopropionic acid (BMPA) to neutralize octreotide with positive charge in physiological conditions. The BMPA-conjugated octreotide was identified by measuring the molecular mass with liquid chromatography-mass spectrometry. In the interaction study with PLGA, native octreotide showed initial adsorption to PLGA and substantial production of acylated peptides (56% of overall peptide), whereas BMPA-conjugated octreotide showed minimal adsorption to PLGA and no acylation products for 42 days. Consequently, the neutralization of octreotide completely inhibited the peptide acylation by preventing interaction of peptide with PLGA. In conclusion, this study demonstrates that the initial polymer interaction of peptide is important step for peptide acylation in PLGA matrix and suggests the modulation of peptide charge as strategy for inhibiting the formation of acylated peptide impurities.

• Journal of Pharmaceutical Investigation
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• v.40 no.4
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• pp.251-254
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• 2010

The formation of acylated peptide impurities in poly(lactide-co-glycolide) (PLGA) formulations is one of the major challenges to the development of successful sustained-release product. Octreotide, synthetic analogue of somatostatin, has been identified to be acylated in PLGA microsphere formulations. The purpose of this study was to investigate the pH effect on the formation of acylated octreotides by PLGA. In the incubation with PLGA in 0.1 M phosphate buffer at pH 7.4, approximately 98% of octreotide adsorbed to PLGA through 14 days and 66.3% of acylated octreotides were produced after 42 days, whereas the interaction of octreotide with PLGA was significantly inhibited in the incubation at pH 4, in which the acylated octreotides were observed to be 9.2% after 42 days. In the interaction study at pH 4.1-7.4, the production of acylated octreotides was demonstrated to be dependent on environmental pH. Below pH 5.0, the acylation of octreotide was significantly inhibited. This study indicates that the pH is the major factor for the formation of acylated octreotide in PLGA formulations.

• Clinical and Experimental Pediatrics
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• v.50 no.3
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• pp.298-301
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• 2007

Chylothorax is a rare complication following cardiac surgery for congenital heart diseases. Although conservative management is successful in the majority of cases, surgical intervention is required in a refractory one. Recently, subcutaneous or intravenous infusion of octreotide has been used as a safe treatment that helps avoiding surgical intervention. Herein, we report two cases of postoperative chylothorax treated with parenteral octreotide and conservative therapy.

• Journal of Hospice and Palliative Care
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• v.12 no.4
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• pp.194-198
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• 2009

Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea Purpose: Malignant bowel obstruction causes gastrointestinal symptoms and leads to diminished quality of life in patients with advanced cancer. Several studies have shown the efficacy of octreotide for the relief of malignant bowel obstruction-related symptoms. The aim of this study is to assess the efficacy and safety of octreotide in patients with malignant bowel obstruction. Methods: We retrospectively reviewed medical records of twenty nine patients who had suffered from malignant bowel obstruction without clinical improvement of conservative care and subsequently, received octreotide treatment. Initial dosage of octreotide was 0.1 mg/day, and dose was escalated depending on the clinical effect. For each patient, we assessed visual analogue scale (VAS) of pain, number of vomiting episode, and amount of nasogastric tube drainage. Results: Median dosage of octreotide was 0.2 mg/day (range 0.1~0.6), and median duration from initial medication to death was 20 days (range 2~103). VAS before and after octreotide treatment were 5.6$\pm$1.24, and 2.7$\pm$0.96, respectively. The numbers of vomiting episode before and after octreotide treatment were 3.6/day$\pm$2.5, and 0.4/day$\pm$0.8, respectively. The mean amounts of nasogastric tube drainage before and after octreotide treatment were 975$\pm$1,083 cc/day and 115$\pm$196 cc/day, respectively. Statistically significant reduction in VAS, the number of vomiting episode and the amount of nasogastric tube drainage were observed after octreotide treatment (P<0.05). Conclusion: Administration of octreotide in patients with malignant bowel obstruction, which is uncontrolled by other medication, was effective and safe. In such clinical situations, physicians should consider to add of octreotide for symptomatic control.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7107-7110
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• 2013

Malignant bowel obstruction (MBO), an occasional complication in patients with advanced urological cancer, causes gastrointestinal symptoms such as nausea and vomiting leading to suffering which severely impairs quality of life (QOL). Drug therapy, especially octreotide, a synthetic analog of somatostatin, is reportedly effective in controlling the symptoms of MBO. In the present study, we administered octreotide to urological cancer patients with MBO and evaluated the improvement of subjective symptoms, oral intake, and nasogastric intubation. Fourteen terminally ill urological cancer patients suffering with MBO were included (age range 55-92, 10 male, 4 female). Octreotide was administered at $300{\mu}g/day$ to those patients subcutaneously as a continuous injection. Significant improvements in subjective symptoms were observed in thirteen patients (92.8%), and ten patients (71.4%) were able to resume oral intake. Four patients required nasogastric drainage before the administration of octreotide, but nasogastric intubation was discontinued in all these cases after the use of octreotide. Early initiation of octreotide resulted in better improvement of MBO symptoms, and no adverse event was observed in any of the patients. These results revealed that $300{\mu}g/day$ dose of octreotide is safe and effective for managing gastrointestinal symptoms of terminally ill urological cancer patients with MBO. We also recommend starting the treatment with ocreotide as soon as MBO is diagnosed.

• Clinical and Experimental Pediatrics
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• v.51 no.11
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• pp.1172-1178
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• 2008

Purpose : Congenital chylothorax is an accumulation of lymphatic fluid within the pleural space. It is a common cause of unidentified hydrops fetalis. We examined the perinatal history, clinical manifestation, diagnosis, treatment, and outcome in 6 newborns diagnosed to have congenital chylothorax with hydrops fetalis. We also studied the effect of octreotide therapy for congenital chylothorax in relation to conservative treatment. Methods : We retrospectively reviewed the medical records of 6 patients diagnosed to have congenital chylothorax with hydrops fetalis among 27,907 newborns who were born at the Cheil General Hospital and Womens Healthcare Center between January 2004 and July 2007. The diagnosis of chylothorax is based on the analysis of pleural fluid before and after milk feeding. Results : Incidence of congenital chylothorax in this study was 0.021%. All 6 cases were noted in over the 92% lymphocyte in pleural analysis. Transudate was changed into chyle with increasing triglyceride levels above 200 mg/dL after milk feeding. Three of 6 infants improved with conservative treatment, including thoracostomy and assisted ventilation. The others had persistent symptoms despite conservative treatment and responded to octreotide therapy. A complication, specifically vomiting was noted in 1 case during octreotide therapy. Conclusion : In this study, octreotide therapy resulted in a safe and excellent outcome. Therefore, octreotide therapy is considered in severe refractory congenital chylothorax in conservative treatment. Further studies are required to determine appropriate guidelines for octreotide therapy.

• Journal of Pharmaceutical Investigation
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• v.39 no.5
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• pp.353-357
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• 2009

As a synthetic analog of the naturally occurring hormone somatostatin, octreotide has been commercially formulated in poly(lactide-co-glycolide) (PLGA) microspheres for the treatment of acromegaly. The purpose of this study was to evaluate stability of octreotide acetate in aqueous solutions at various pH values and PLGA films. Stability-indicating reversed-phase high-performance liquid chromatographic method was developed with good precision and accuracy, and it was applied to the stability studies. In aqueous solutions at pH 2.5-9.0, the degradation of octreotide followed approximately first order kinetics and the most favorable stability was found at pH 4. In PLGA films, the formation of acylated octreotides reached approximately 55% of the released octreotides. Various acylated octreotides was structurally identified by liquid chromatography-mass spectrometric analysis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3191-3194
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• 2012

Objective: To investigate the association between the change of IGF-2 level in serum after transcatheter arterial chemoembolization (TACE) and hepatocellular carcinoma (HCC) progression, especially in relation to metastasis. Methods: IGF-2 in serum was measured by quantitative sandwich enzyme-linked immunosorbent assaybefore, 3 days and 4 weeks after TACE in 60 patients with HCC. The occurrence of HCC metastasis was also evaluated, 3 months after TACE. Results: (1) The average serum level of IGF-2 in the 60 patients with HCC was $136.5{\pm}87.3$ pg/ml; (2) A tendency for increase was observed with heterogenous uptake of octreotide and portal vein thrombosis. Metastatic foci were found in 37/38 patients in the group with IGF-2 increasing (97.0%), in contrast to 3/22 (13.6%) patients with IGF-2 decrease. Conclusion: The increase of IGF-2 level in serum appears to be associated with the occurrence of metastatic HCC after TACE and chemotherapy.

• Journal of Chest Surgery
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• v.38 no.2 s.247
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• pp.172-174
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• 2005

Chylothorax is a rare but serious and well-recognized complication of thoracic and cardiac procedures. A postoperative chylothorax developed in a 3-month-old male patient after ligation of patent ductus arteriosus and repair of coarctation of aorta. He was treated successfully with conservative management using a combination of parenteral octreotide and medium-chain triglyceride (MCT) -enriched fomula with pleural drainage. We report a case of successful conservative treatment using octreotide for postoperative chylothorax.