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Digestion 1999
Topics: Gastrointestinal Agents; Gastrointestinal Diseases; Hormones; Humans; Octreotide
PubMed: 10357620
DOI: 10.1159/000051482 -
Journal of Nuclear Medicine : Official... Apr 2016In peptide receptor radionuclide therapy with (90)Y-labeled DOTATATE, the kidney absorbed dose limits the maximum amount of total activity that can be safely...
UNLABELLED
In peptide receptor radionuclide therapy with (90)Y-labeled DOTATATE, the kidney absorbed dose limits the maximum amount of total activity that can be safely administered in many patients. A higher tumor-to-kidney absorbed dose ratio might be achieved by optimizing the amount of injected peptide and activity, as recent studies have shown different degrees of receptor saturation for normal tissue and tumor. The aim of this work was to develop and implement a modeling method for treatment planning to determine the optimal combination of peptide amount and pertaining therapeutic activity for each patient.
METHODS
A whole-body physiologically based pharmacokinetic (PBPK) model was developed. General physiologic parameters were taken from the literature. Individual model parameters were fitted to a series (n= 12) of planar γ-camera and serum measurements ((111)In-DOTATATE) of patients with meningioma or neuroendocrine tumors (NETs). Using the PBPK model and the individually estimated parameters, we determined the tumor, liver, spleen, and red marrow biologically effective doses (BEDs) for a maximal kidney BED (20 Gy2.5) for different peptide amounts and activities. The optimal combination of peptide amount and activity for maximal tumor BED, considering the additional constraint of a red marrow BED less than 1 Gy15, was individually quantified.
RESULTS
The PBPK model describes the biokinetic data well considering the criteria of visual inspection, the coefficients of determination, the relative standard errors (<50%), and the correlation of the parameters (<0.8). All fitted parameters were in a physiologically reasonable range but varied considerably between patients, especially tumor perfusion (meningioma, 0.1-1 mL·g(-1)·min(-1), and NETs, 0.02-1 mL·g(-1)·min(-1)) and receptor density (meningioma, 5-34 nmol·L(-1), and NETs, 7-35 nmol·L(-1)). Using the proposed method, we identified the optimal amount and pertaining activity to be 76 ± 46 nmol (118 ± 71 μg) and 4.2 ± 1.8 GBq for meningioma and 87 ± 50 nmol (135 ± 78 μg) and 5.1 ± 2.8 GBq for NET patients.
CONCLUSION
The presented work suggests that to achieve higher efficacy and safety for (90)Y-DOATATE therapy, both the administered amount of peptide and the activity should be optimized in treatment planning using the proposed method. This approach could also be adapted for therapy with other peptides.
Topics: Adult; Aged; Aged, 80 and over; Bone Marrow; Computer Simulation; Female; Gamma Cameras; Humans; Kidney; Male; Meningioma; Middle Aged; Models, Biological; Models, Theoretical; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin; Regional Blood Flow; Tissue Distribution; Yttrium Radioisotopes
PubMed: 26678617
DOI: 10.2967/jnumed.115.164699 -
Gut 1994Morbidity and mortality related to pancreatic surgery are still high: 30-40% and 3-10% respectively. As most complications are probably related to exocrine pancreatic... (Review)
Review
Morbidity and mortality related to pancreatic surgery are still high: 30-40% and 3-10% respectively. As most complications are probably related to exocrine pancreatic secretion, its inhibition could improve the postoperative course. In 1979, Klempa saw a low complication rate after Whipple resection in a small number of patients treated with somatostatin, a powerful inhibitor of pancreatic exocrine secretion. The long acting somatostatin analogue, octreotide, also inhibits pancreatic exocrine secretion and can be given by subcutaneous injections. Two double blind, placebo controlled, multicentre studies with randomisation into parallel groups were recently performed to find out if peri and postoperative administration of octreotide (100 micrograms thrice daily subcutaneously) reduces the rate of complications specifically related to pancreatic surgery. Both trials consistently showed that octreotide can reduce substantially (over 40%) the risk of complications in these patients; the treatment acceptability was good.
Topics: Clinical Trials as Topic; Humans; Multicenter Studies as Topic; Octreotide; Pancreas; Postoperative Complications; Somatostatin
PubMed: 7911443
DOI: 10.1136/gut.35.3_suppl.s20 -
International Journal of Surgery... 2013A best evidence topic was written according to a structured protocol. The question addressed was whether the prophylactic administration of somatostatin or somatostatin... (Review)
Review
A best evidence topic was written according to a structured protocol. The question addressed was whether the prophylactic administration of somatostatin or somatostatin analogues in patients undergoing pancreaticoduodenectomy (Whipple's procedure) is beneficial in terms of improved surgical outcomes, reduced morbidity or reduced mortality. A total of 118 papers were found using the reported searches of which 5 represented the best evidence (1 meta-analysis, 1 systematic review and 3 randomized control trials). The authors, date, journal, study type, population, main outcome measures and results were tabulated. There is evidence that the perioperative administration of somatostatin or somatostatin analogues reduces biochemical incidence of pancreatic fistula but, it is still unclear if there is a beneficial effect in the incidence of clinically significant pancreatic fistula. Further adequately powered trials with low risk of bias are necessary. From the available data, somatostatin or somatostatin analogues have no effect on mortality post Whipple's. Interestingly, there are only limited data available on the cost-benefit and financial constraints imposed by this treatment, an issue that has only been addressed in a few studies.
Topics: Gastrointestinal Agents; Humans; Octreotide; Pancreas; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 23800512
DOI: 10.1016/j.ijsu.2013.06.013 -
Oncotarget Dec 2016Cardiac glycosides could increase intracellular Ca2+ ion by inhibiting the Na+/K+ATPase to induce apoptosis in many tumor cells. However, narrow therapeutic index, poor...
Cardiac glycosides could increase intracellular Ca2+ ion by inhibiting the Na+/K+ATPase to induce apoptosis in many tumor cells. However, narrow therapeutic index, poor tumor selectivity and severe cardiovascular toxicity hinder their applications in cancer treatment. To improve the safety profile and tumor targetablility of cardiac glycosides, we designed octreotide conjugated periplocymarin, a cardiac glycoside isolated from Cortex periplocae. The conjugate showed higher cytotoxicity on MCF-7 cells and HepG2 tumor cells (SSTRs overexpression) but much less toxicity in L-02 normal cells. Tissue distribution studies of the conjugate using H22 tumor model in mice showed higher accumulation in tumor and lower distribution in heart and liver than periplocymarin. Furthermore, in vivo anticancer effects of the conjugate on mice bearing H22 cancer xenografts confirmed enhanced anti-tumor efficacy and decreased systemic toxicity. Altogether, octreotide-conjugated periplocymarin demonstrated tumor selectivity and may be useful as a targeting agent to improve the safety profile of cardiac glycosides for cancer therapy.
Topics: Animals; Antineoplastic Agents; Cardiac Glycosides; Cell Line, Tumor; Humans; Male; Mice; Neoplasms, Experimental; Octreotide; Prodrugs; Tissue Distribution
PubMed: 27861145
DOI: 10.18632/oncotarget.13389 -
Turkish Neurosurgery Jan 2010To investigate the effects of melatonin and octreotide in the prevention of peridural fibrosis in an experimental rat model.
AIM
To investigate the effects of melatonin and octreotide in the prevention of peridural fibrosis in an experimental rat model.
MATERIAL AND METHODS
A total of 36 rats were divided into three groups: Group I was laminectomized and not given any treatment. Group II received an intraperitoneal 30 microg/kg/day dose of octreotide for six weeks after the laminectomy. Group III rats were injected with melatonin 7.5 mg/kg/day for six weeks after the laminectomy. At the end of six weeks, plasma transforming growth factor beta-1 levels and peridural fibrous tissue hydroxyproline concentrations were determined and histopathological examinations was performed.
RESULTS
Serum TGF-Beta1 levels of the octreotide and melatonin groups were found to be lower than the control group. The lower levels of TGF-Beta1 was statistically significant in both of the groups. Hydroxyproline levels of the octreotide and melatonin groups were found to be lower than that of the control group. The decrease was statistically significant only in the melatonin group. Peridural fibrosis scores of the octreotide and melatonin groups were lower than the control group. This histopathological improvement was statistically significant only in the melatonin group.
CONCLUSION
Melatonin and octreotide prevented TGF-Beta1 increase in peridural fibrosis, but only melatonin significantly improved hyroxyproline levels and fibrosis scores as demonstrated.
Topics: Animals; Central Nervous System Depressants; Fibrosis; Laminectomy; Lumbar Vertebrae; Male; Melatonin; Octreotide; Rats; Rats, Wistar; Transforming Growth Factor beta1
PubMed: 20066622
DOI: No ID Found -
HPB Surgery : a World Journal of... 1998In healthy subjects octreotide is largely metabolised by the liver suggesting that the plasma half-life of the somatostatin analogue may be prolonged in patients with... (Comparative Study)
Comparative Study
Pharmacokinetics of octreotide in patients with cirrhosis and portal hypertension; relationship between the plasma levels of the analogue and the magnitude and duration of the reduction in corrected wedged hepatic venous pressure.
In healthy subjects octreotide is largely metabolised by the liver suggesting that the plasma half-life of the somatostatin analogue may be prolonged in patients with hepatic dysfunction. The aim of this study was therefore (a) to determine the pharmacokinetics of octreotide following its subcutaneous injection in 6 patients with cirrhosis and portal hypertension and (b) compare the magnitude and duration of the effects of intravenous administration of 250 micrograms somatostatin and 50 micrograms octreotide on corrected wedged hepatic venous pressure (WHVP) and to relate the findings to the plasma levels of the analogue 1 h after administration in 13 patients with cirrhosis and portal hypertension. Following subcutaneous administration of 50 micrograms octreotide the circulating half life (range 2.4 to 4.79 h) was prolonged whereas the clearance (range 2.101 to 4.775 L/h) was decreased compared to healthy controls. Intravenous bolus administration of 250 micrograms somatostatin or 50 micrograms octreotide resulted in a reduction in WHVP of approximately the same magnitude and duration despite appreciable quantities of the analogue in the blood 1 h after administration (1944 +/- 226 pg/ml). These results indicate that the circulating half-life of octreotide is prolonged in cirrhotics suggesting that the dosage regimens should be modified in such patients to avoid accumulation of the analogue in the blood which may result in undesirable side-effects or toxicity. Furthermore, since the magnitude and duration of the reduction in WHVP elicited by IV octreotide is similar to that observed with somatostatin, the analogue, like the native hormone, must be administered by continuous IV infusion to produce a sustained response and hence a therapeutic effect in the management of acute variceal bleeding.
Topics: Blood Pressure; Female; Half-Life; Hepatic Veins; Hormones; Humans; Hypertension, Portal; Injections, Intravenous; Injections, Subcutaneous; Liver Cirrhosis; Male; Octreotide; Somatostatin; Statistics, Nonparametric; Time Factors
PubMed: 9830576
DOI: 10.1155/1998/17436 -
The Journal of Pediatrics Oct 1993Octreotide, a long-acting analog of somatostatin that inhibits insulin release, has the potential to control hypoglycemia in infants with congenital hyperinsulinism. To...
Octreotide, a long-acting analog of somatostatin that inhibits insulin release, has the potential to control hypoglycemia in infants with congenital hyperinsulinism. To examine the efficacy and side effects of octreotide, we evaluated therapy between 1988 and 1993 in 16 infants who did not respond to diazoxide. In nine patients with onset of severe hypoglycemia in the first days of life, octreotide was helpful in stabilizing plasma glucose levels and allowed reductions in the rates of glucose infusion; however, glucose control was inadequate to avoid subtotal pancreatectomy. In two of these nine patients postoperatively and in seven other infants, a trial of long-term treatment with octreotide was undertaken. Four were treated successfully for up to 4.3 years. Octreotide therapy was not associated with thyroid deficiency and caused only transient malabsorption. All patients receiving long-term therapy had some decrease in linear growth and two had subnormal plasma concentrations of insulin-like growth factor I and insulin-like growth factor binding protein 3 compatible with suppression of growth hormone by octreotide. Resistance to octreotide therapy, even with increasing doses, occurred in all patients. These results suggest that octreotide may aid in the acute or long-term treatment of congenital hyperinsulinism in a limited number of selected cases.
Topics: Diazoxide; Female; Follow-Up Studies; Glucagon; Glucose; Growth Disorders; Humans; Hyperinsulinism; Hypoglycemia; Infant, Newborn; Male; Octreotide; Pancreatectomy; Time Factors
PubMed: 8410522
DOI: 10.1016/s0022-3476(05)80969-2 -
Journal of Nuclear Medicine Technology Sep 2018
Topics: Humans; Octreotide; Organometallic Compounds; Patient Education as Topic; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Receptors, Peptide
PubMed: 30076242
DOI: 10.2967/jnmt.118.217844 -
The New England Journal of Medicine Nov 1991Patients with scleroderma may have abnormal motility of the small intestine, with pseudoobstruction and bacterial overgrowth. Standard stimulatory agents are often...
BACKGROUND
Patients with scleroderma may have abnormal motility of the small intestine, with pseudoobstruction and bacterial overgrowth. Standard stimulatory agents are often ineffective in such patients. Because the somatostatin analogue octreotide evokes intestinal motor activity in normal subjects, we hypothesized that it might increase motility in patients with scleroderma.
METHODS
We studied the effects of octreotide on intestinal motility and plasma motilin concentrations in five fasting patients with scleroderma who had bacterial overgrowth and in six fasting normal subjects. The motor effects of octreotide were correlated with its effects on abdominal symptoms and bacterial overgrowth as determined by the level of breath hydrogen excretion.
RESULTS
In the normal subjects, octreotide (10 micrograms subcutaneously) increased the mean (+/- SD) frequency of intestinal migrating complexes, which reflect intestinal motility, from 1.5 +/- 1.0 to 4.1 +/- 1.1 every three hours. In the patients with scleroderma, who had no spontaneous migrating complexes, octreotide (100 micrograms) induced 3.6 +/- 2.3 complexes every three hours. These complexes propagated at the same velocity and had two-thirds the amplitude of the spontaneous complexes in normal subjects. Plasma motilin concentrations, which were higher in the patients with scleroderma (229 +/- 74 pmol per liter) than in the normal subjects (112 +/- 37 pmol per liter), were inhibited by octreotide, suggesting that intestinal activity evoked by octreotide is independent of motilin. Treatment of the patients with scleroderma with octreotide (50 micrograms every evening) for three weeks reduced breath hydrogen excretion while they were fasting from 25 +/- 5 to 4 +/- 2 ppm (P = 0.001) and breath hydrogen excretion after they ingested 50 g of glucose from 46 +/- 24 to 8 +/- 7 ppm (P = 0.015); these reductions were accompanied by a significant decrease in nausea, bloating, and abdominal pain and by less frequent emesis.
CONCLUSIONS
Octreotide stimulates intestinal motility in normal subjects and in patients with scleroderma. In such patients, the short-term administration of octreotide reduces bacterial overgrowth and improves abdominal symptoms. This agent may be useful for the treatment of intestinal dysmotility in patients with scleroderma.
Topics: Adult; Aged; Breath Tests; Duodenum; Female; Gastrointestinal Motility; Humans; Hydrogen; Intestine, Small; Male; Manometry; Middle Aged; Motilin; Octreotide; Scleroderma, Systemic; Stimulation, Chemical
PubMed: 1944424
DOI: 10.1056/NEJM199111213252102