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Pharmacotherapy 1998Because of deleterious hemodynamic effects of octreotide in a nonacromegalic patient with a pancreatic fistula, we conducted a MEDLINE search of English-language journal...
Because of deleterious hemodynamic effects of octreotide in a nonacromegalic patient with a pancreatic fistula, we conducted a MEDLINE search of English-language journal articles to extract information on this complication of octreotide or somatostatin therapy. Few data are available regarding patients with disease states other than acromegaly. We believe octreotide should be considered when determining the cause of bradycardia.
Topics: Adult; Anemia, Hemolytic; Antineoplastic Agents, Hormonal; Bradycardia; Cardiovascular Diseases; Female; Humans; Octreotide
PubMed: 9545165
DOI: No ID Found -
Pediatric Critical Care Medicine : a... Nov 2006We review physiology and pharmacology relating to the use of octreotide for chylothorax in infants and children. We review the published experience of octreotide dosing... (Review)
Review
OBJECTIVES
We review physiology and pharmacology relating to the use of octreotide for chylothorax in infants and children. We review the published experience of octreotide dosing in this context.
DATA SOURCE
Systematic review of the literature, including PubMed (English-only journals), citations from relevant articles, major textbooks, and personal files.
CONCLUSIONS
Octreotide has been used as a successful therapeutic adjunct in a small number of neonatal cases and a larger number of pediatric cases. No consensus has been reached as to the optimal route of administration, dose, duration of therapy, or strategy for discontinuation of therapy. We suggest using higher doses (80-100 microg/kg/day) and initiating therapy early rather than using a low initial dose with upward titration. Duration of therapy required to elicit a significant response may vary between patients.
Topics: Antineoplastic Agents, Hormonal; Child; Chylothorax; Humans; Infant; Infant, Newborn; Octreotide
PubMed: 16878051
DOI: 10.1097/01.PCC.0000235256.00265.C8 -
Journal of Paediatrics and Child Health 2004Congenital chylothorax is the accumulation of lymphatic fluid within the pleural space. Cases unresponsive to conservative management usually require surgery. Octreotide... (Review)
Review
Congenital chylothorax is the accumulation of lymphatic fluid within the pleural space. Cases unresponsive to conservative management usually require surgery. Octreotide has been used successfully to treat post-traumatic chylothoraces in the paediatric and adult population. Its exact mode of action is uncertain but it is believed to reduce lymphatic drainage by a direct action on splanchnic lymph flow. We report a case of congenital chylothorax where surgery was avoided with the compassionate trial of the somatostatin analogue, octreotide. Treatment was associated with prompt respiratory improvement prior to cessation of pleural drainage. Further studies are required to ascertain its true value in congenital chylothorax.
Topics: Chylothorax; Dose-Response Relationship, Drug; Gastrointestinal Agents; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Octreotide; Time Factors; Treatment Outcome
PubMed: 15367160
DOI: 10.1111/j.1440-1754.2004.00471.x -
Current Pharmaceutical Design 2011The finding that somatostatin (SST) or its analogue, octreotide caused a dose-dependent reduction in exocrine pancreatic secretions triggered their research as... (Review)
Review
The finding that somatostatin (SST) or its analogue, octreotide caused a dose-dependent reduction in exocrine pancreatic secretions triggered their research as therapeutic options for acute pancreatitis (AP), a life-threatening illness. However, the accumulative clinical trials of SST or octreotide in AP treatment present the controversial results. The insufficient secretory capacity of acinar cells in AP patients also queries the validity of traditional assumption on the effects of SST and octreotide. This reviewer updates the current pharmacological concepts of SST and octreotide in treatment of AP and the clinical strategies of their application. The impressive inhibitive effects on the massive inflammatory injury via the several signal pathways make SST as an important anti-inflammatory peptide. Furthermore, endocrine SST may decrease the sphincter tone of Oddi (SO) by its potential role on the neurocrine of SST in SO. Therefore, it should be rational that exogenous supplement of SST or octreotide for AP patients due to the plasma level of SST during AP is usually lower than that of normal. In accordance with these findings, the optimal stage of SST or octreotide administration, application in high risk population, the cost-effective dosage or duration as well as the design of suitable clinical outcomes would be the interesting topics of translational medical research for both basic scientists and clinicians.
Topics: Acute Disease; Humans; Octreotide; Pancreatitis; Somatostatin
PubMed: 21548873
DOI: 10.2174/138161211796196936 -
Deutsche Medizinische Wochenschrift... Jul 1995
Topics: Humans; Octreotide
PubMed: 7628318
DOI: 10.1055/s-0029-1234210 -
Gastroenterology Jan 2001
Review
Topics: Gastrointestinal Agents; Humans; Octreotide; Portal System
PubMed: 11208741
DOI: 10.1053/gast.2001.21619 -
Archives of Razi Institute Feb 2023Sepsis is a systemic inflammatory consequence resulting from microbial infection, assessed as a worldwide healthcare issue. Sepsis can result in multiorgan dysfunction,...
Sepsis is a systemic inflammatory consequence resulting from microbial infection, assessed as a worldwide healthcare issue. Sepsis can result in multiorgan dysfunction, including cardiac, renal, hepatic, and cerebral dysfunction. Cardiotoxicity can occur in humans and rodents during sepsis, leading to increased mortality. The current study aims to explore the possible cardioprotective effects of octreotide during sepsis-induced cardiotoxicity. This study was done with a total of forty male albino Swiss mice, aged 8-12 weeks and weighing 25-30 gm. These animals had free access to food and water. After two weeks of adaptation, mice were divided into four groups (n=10): 1) Normal group: healthy mice; 2) CLP group: mice underwent CLP operation; 3) Vehicle group: mice received DMSO. 4) Octreotide group: mice received octreotide (10 mg/kg) subcutaneously in 2 divided doses for 5 consecutive days. All groups underwent CLP operation on the 4th day, then sacrificed on the 5th day then blood, and tissue sampling was done. The Octreotide group demonstrated a significant (<0.05) decrease in the myocardial levels of cardiac troponin-I as compared to the CLP group. Furthermore, the octreotide group demonstrated a significant (<0.05) decrease in the serum level of inflammatory cytokines (TNF-α, IL-6, & IL-1β) as compared to the CLP group. Additionally, the octreotide group showed a significant (<0.05) elevation in the myocardial activity of SOD and a reduction in MDA level compared to the CLP group. Histologically, all mice in the CLP group showed a significant (<0.05) cardiac tissue injury, while the octreotide groups showed a significant (<0.05) reduced level of cardiac tissue injury. The results of the present study revealed that octreotide attenuates sepsis-induced cardiotoxicity through different protective effects; they include the anti-inflammatory effect through their ability to decrease serum levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6). Also, the anti-oxidant effect through their ability to decrease myocardial levels of MDA and increase the myocardial activity of SOD. Additionally, the direct cardiac protective effect through the lower level of cardiac troponin- I and the reduction of histopathological changes during sepsis-induced cardiotoxicity.
Topics: Animals; Male; Mice; Cardiotoxicity; Cytokines; Interleukin-6; Octreotide; Sepsis; Superoxide Dismutase; Tumor Necrosis Factor-alpha
PubMed: 37312717
DOI: 10.22092/ARI.2022.358339.2201 -
Materials Science & Engineering. C,... Sep 2019Poly(d,l-lactide-co-glycolide) (PLGA) microspheres have been used as an injectable depot for prolonged release of octreotide (Sandostatin LAR®), a peptide drug for the...
Poly(d,l-lactide-co-glycolide) (PLGA) microspheres have been used as an injectable depot for prolonged release of octreotide (Sandostatin LAR®), a peptide drug for the treatment of acromegaly and gastrointestinal tumors. However, acylation and incomplete release of the encapsulated octreotide, as well as acidic degradation product-induced inflammation are the major challenges hampering widespread clinical applications of this delivery system. The purpose of this study was to develop a novel octreotide-delivering system utilizing naturally derived biodegradable material, silk fibroin (SF). Octreotide acetate was encapsulated in the SF microspheres with a high loading (8-10 wt%) using polyethylene glycol (PEG)-assisted emulsification method. The octreotide-SF microspheres exhibited a silk I structure (low crystallinity) and burst release in in vitro release studies. Ethanol treatment after microsphere formation significantly increased β-sheet and silk II structure (high crystallinity) of the microspheres, significantly reducing the burst release and resulting in zero-order sustained release of octreotide over 102 days, and the data could be fit to the diffusion-driven release model. After the ethanol-treated microspheres were intramuscularly injected into rats at low (2 mg/kg) and high (8 mg/kg) octreotide doses, the plasma concentration of octreotide in the high dose group remained high (>50 pg/mL) at day 28 when compared to that of the control (pure drug at low dose) and low dose microsphere group. Interestingly, the plasma concentration for the high dose group at day 56 dramatically increased to >280 pg/mL observed at day 28. The low dose microsphere group showed a similar increase, but at a much lower level. The rebound octreotide level likely reflected degradation of the SF matrix which released tightly bound/trapped octreotide. Therefore, SF microspheres can deliver octreotide over a long period of time with release kinetics and the mechanism different from PLGA microsphere system.
Topics: Animals; Bombyx; Drug Liberation; Ethanol; Female; Fibroins; Methanol; Microspheres; Octreotide; Particle Size; Rats, Sprague-Dawley
PubMed: 31147054
DOI: 10.1016/j.msec.2019.05.004 -
Clinical Pharmacokinetics Nov 1993Among somatostatin analogues, octreotide is the most extensively studied. Its pharmacodynamic properties are similar to those of somatostatin, with a wide spectrum of... (Review)
Review
Among somatostatin analogues, octreotide is the most extensively studied. Its pharmacodynamic properties are similar to those of somatostatin, with a wide spectrum of inhibitory effects on anterior pituitary function, pancreas and gut endocrine secretions, and gastrointestinal functions. Compared with the somatostatin, octreotide is highly resistant to enzymatic degradation and has a prolonged plasma half-life of about 100 minutes in humans, allowing its use in the long term treatment of various pathological conditions. Differential effects of octreotide on endocrine secretions such as growth hormone (GH) and insulin in healthy volunteers, as well as variable efficacy in the treatment of endocrine tumours, may relate to the distribution of somatostatin receptor subtypes. The volume of distribution of octreotide ranges from 18 to 30L. Calculated serum distribution half-life ranges from 72 to 98 minutes. In blood, octreotide is mainly distributed in the plasma, 65% being bound to lipoproteins. After subcutaneous injection, absorption appears rapid and complete and bioavailability is about 100%. Mean peak plasma concentrations are between 2 and 4 micrograms/L in patients receiving 50 to 100 micrograms. Peak concentrations are reached within 20 to 30 minutes and are 20 to 40% of corresponding values after intravenous injection. Peak concentrations and values for areas under the plasma concentration-time curve linearly correlate with the dosage. The elimination half-life is about 90 to 110 minutes. Total clearance in healthy individuals is about 160 ml/min (9.6 L/h). Hepatic metabolism of octreotide is extensive (30 to 40%) and about 11 to 20% of the dose is excreted unchanged in the urine. Among pituitary tumours, GH- and thyrotrophin-secreting adenomas are the most sensitive to octreotide. Octreotide has been widely used in the treatment of acromegaly. 50 to 80% of the patients respond to daily multiple subcutaneous injections with insulin-like growth factor-1 (IGF1) levels being normalised in about 40 to 50% of them. Neither desensitisation with long term therapy nor rebound phenomena after octreotide withdrawal have been noticed in these studies. Even in patients with partial response, clinical symptoms improved. Octreotide daily dosages needed to achieve optimum responses may vary greatly from one patient to another. In a minority of patients complete resistance to octreotide was observed and was not always related to the absence of somatostatin receptors in the tumour. The wide spectrum of effects of octreotide in humans accounts for adverse effects seen during long term treatment, primarily cholelithiasis. Other modes of administration are efficient.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Amino Acid Sequence; Drug Tolerance; Humans; Molecular Sequence Data; Octreotide; Pituitary Neoplasms; Structure-Activity Relationship
PubMed: 8287633
DOI: 10.2165/00003088-199325050-00004 -
Expert Opinion on Therapeutic Patents 2016New low-cost strategies and enhancement of the already described methods to manufacture peptide molecules on an industrial scale are highly requested, particularly for... (Review)
Review
INTRODUCTION
New low-cost strategies and enhancement of the already described methods to manufacture peptide molecules on an industrial scale are highly requested, particularly for peptides such as octreotide, which, along with goserelin and leuprolide, dominate the global peptide market. A number of patents related to the production of octreotide can be found, concerning both solution and solid-phase synthesis. Thus, there is a need to revise the existing synthetic approaches in order to organize them in a more comprehensible way.
AREA COVERED
The octreotide patent landscape could help improvement of the methods for manufacturing of octreotide in industrial scale, leading to the appearance of innovative approaches.
EXPERT OPINION
The pharmaceutical value of octreotide can be seen from its high market percentage among other peptide drugs. The complex chemical structure of octreotide represents the main challenge for its industrial production. Two synthetic steps are crucial in the preparation of octreotide: (i) threoninol attachment or on resin formation working in solid-phase and (ii) disulphide bond formation to achieve cyclic structure. Analysis of various patents filed to date allows us to see the trend in simplification of the synthetic approaches from the labor intensive syntheses in solution to the more versatile and rapid solid-phase methods.
Topics: Chemistry, Pharmaceutical; Drug Industry; Drugs, Generic; Humans; Octreotide; Patents as Topic; Peptides
PubMed: 26924267
DOI: 10.1517/13543776.2016.1158810