Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Octreotide (Sandostatin) is a synthetic analog of somatostatin, an endogenous GH inhibitory peptide that has been used as an adjunct to surgery and radiotherapy in the treatment of acromegaly. When given sc in divided daily doses, it lowers serum GH to less than 5 micrograms/L in approximately 50% of cases. Data suggest that continuous infusions of somatostatin analogs may be more effective in lowering GH. We have evaluated Sandostatin-LAR, a new long-acting preparation of Sandostatin, in eight patients with acromegaly. After an initial pharmacokinetic study, patients received a minimum of 10 im injections of Sandostatin-LAR (20, 30, or 40 mg) at 28- or 42-day intervals. Serum GH levels decreased from 10.7 +/- 2.8 micrograms/L (mean +/- SE) at baseline to a nadir of 2.6 +/- 0.4 micrograms/L after the tenth injection, and to less than 5 micrograms/L in every patient. Serum insulin-like growth factor-I decreased from 927 +/- 108 ng/mL at baseline to 472 +/- 59 ng/mL at the end of the sixth injection and returned to normal (< 500 ng/mL) in seven of the eight patients. This was associated with significant improvements in headache, arthralgia, and sweating. There was no evidence of octreotide accumulation, and the drug was well tolerated. To date, no gallstones have occurred, and serial pituitary imaging has revealed no increase in the size of the initial pituitary tumor. In particular, two previously untreated patients have shown complete regression of the initial microadenoma and have serum GH values of less than 2.5 micrograms/L. Sandostatin-LAR is an effective and well-tolerated treatment for patients with acromegaly. Undoubtedly the initial indication for Sandostatin-LAR will be in the patient who is not cured after surgery and radiotherapy, but our experience suggests that it may be used as a primary treatment in some acromegalics.
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PMID:Depot long-acting somatostatin analog (Sandostatin-LAR) is an effective treatment for acromegaly. 759 36

Treatment options for acromegaly include surgical removal of the adenoma, radiotherapy, or pharmacological reduction of growth hormone (GH) levels by dopamine agonists or somatostatin analogs. Whether such treatment can truly cure acromegaly is debatable. A problem with evaluating efficacy of treatment is the lack of consensus of what constitutes a cure. Despite modern neurosurgical techniques for resecting GH-secreting pituitary adenomas, more than 50% of patients may have persistent GH hypersecretion; radiotherapy may take years to produce an effect. There is thus interest in pharmacological relief of symptoms and reduction in GH secretion. We report on eight patients with a biochemical diagnosis of acromegaly (failure of suppression of GH levels to < 2.5 micrograms/L following a glucose tolerance test [GTT]). The use of Sandostatin-LAR (Sandoz Pharma Ltd, Basel, Switzerland) in doses of 20 to 30 mg intramuscularly at 4 week intervals produced consistent and therapeutic serum octreotide concentrations, suppressed GH secretion to 5 micrograms/L in all eight subjects, lowered insulin-like growth factor-1 (IGF-1) levels in all and normalized values in seven of eight, improved or led to disappearance of symptoms and signs, and was not associated with an increase in adverse events as compared with subcutaneous treatment.
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PMID:Treatment options for acromegaly. 876 85

This study was conducted to determine the feasibility of injecting the somatostatin analogue, octreotide acetate (OA), into the vitreous cavity. Previous work suggests that octreotide effectively inhibits angiogenesis in vitro, thus its use in vivo may slow the progression of proliferative eye disease. Fifty micrograms of aqueous OA in 50 microliters aqueous solution was injected into the mid-vitreous of kitten eyes (n = 6), and OA levels were monitored over 4 days. A long-acting release form of octreotide (OA-LAR) was also injected into the mid-vitreous of rabbit eyes at doses of 0.36 (n = 16), 1.1 (n = 1), 2.1 (n = 1), 4.05 (n = 1), 8.2 (n = 1), and 36 mg (n = 3) in solution; and octreotide concentrations were measured at various time points over 42 days. OA concentrations were determined by a highly specific radioimmunoassay. Aqueous octreotide was eliminated rapidly (t1/2 = 16 hours) from the vitreous of the kitten eye, with only negligible amounts recoverable 4 days post-injection. In the long-acting form, OA in the rabbit eye reached peak levels at 28 days. By 42 days, OA levels had declined to the 14-day level. Doses of OA-LAR of 1.1 mg or less produced no gross evidence of clinical toxicity and elicited no grossly visible ocular side effects. Doses greater than 1.1 mg produced significant toxicity, including cataracts and rubeosis. The 28-day peak release for long-acting OA implies that monthly intravitreal injections could provide continual high levels of OA. Intravitreal injection of long-acting OA provides sustained, high concentrations of drug, and deserves further study as a potential treatment of proliferative eye diseases.
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PMID:Intravitreal injection of octreotide acetate. 909 Jun 17

Advances in medical treatment of prolactinomas and acromegaly in the last 20 years are analyzed. Dopaminergic drugs as bromocriptine, lisuride, pergolide and terguride successfully control hyperprolactinemia, reduce tumor size and cause clinical improvement. New long lasting medications with less adverse effects such as cabergoline, with oral weekly administration, and the repeatable monthly injectable form of bromocriptine (Parlodel LAR, Sandoz) may be the treatment of choice for prolactinomas. Dopaminergic medications are less effective in acromegaly. The higher doses required induce more collateral effects. An important step has been the incorporation of long lasting somatostatin analogues such as octreotide (for sbc use tid) intramuscular every 28 days injectable Sandostatin LAR and lanreotide SR (Somatuline, Ipsen Biotech), injectable every 10 to 14 days. Medical treatment of acromegaly is not, at the present, an alternative to surgery. However, the development of long lasting specific drugs may become, in the future, the choice or an alternative in the treatment of acromegaly.
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PMID:[Medical treatment of prolactin and growth hormone-secreting pituitary tumors]. 960 63

Analogs of somatostatin (SRIF) such as octreotide exert antiproliferative effects that are mediated directly by tumoral SRIF receptors or indirectly by down-modulation of factors that stimulate tumor growth. Direct and indirect antiproliferative effects have been demonstrated in certain SRIF receptor-positive and -negative human breast cancer models in nude mice, respectively. These antiproliferative mechanisms are also being explored in other cancer types including pancreatic cancer. While clinical pilot studies have indicated that a fraction of pancreatic adenocarcinomas respond to high-dose octreotide treatment, it is known from receptor autoradiographic and scintigraphic studies that human pancreatic carcinomas fail to express SRIF receptors, in contrast to rat pancreatic carcinomas or human endocrine pancreatic cancer. Studies on the potential anticancer effect of octreotide on the growth of experimental human pancreatic cancer and its SRIF receptor status have been controversial. Therefore, we investigated in vivo the effects of octreotide on the growth of MIA PaCa-2 human pancreatic carcinomas raised from cultured cells with a low passage number after receipt from the American Type Culture Collection. Nude mice bearing MIA PaCa-2 tumors were treated with a single injection of the recently developed octreotide long-acting release formulation, "SMS pa LAR." This treatment was well tolerated and resulted in a highly significant inhibition of tumor growth during weeks three and eight after administration. MIA PaCa-2 tumors were removed after eight weeks and processed for RT-PCR analysis using probes specific for each of the five somatostatin receptor subtypes sst1-sst5. This analysis revealed that MIA PaCa-2 tumors, like human pancreatic adenocarcinomas, do not express any of the five SRIF receptor subtypes, suggesting an indirect mode of tumor growth inhibition. In summary, the depot formulation SMS pa LAR exerted long-lasting antiproliferative effects in SRIF receptor-negative human pancreatic carcinomas in nude mice.
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PMID:Indirect antiproliferative effect of the somatostatin analog octreotide on MIA PaCa-2 human pancreatic carcinoma in nude mice. 982 82

Octreotide (octreotide-acetate, Sandostatin(R)) is a somatostatin analogue, used in long-term treatment of acromegaly. The present study describes the absorption profile in rabbits of octreotide after release from the long-acting formulation OncoLAR (denoted as octreotide-LAR). In a first experiment, the disposition kinetics of octreotide was studied for 24 h in six rabbits after intravenous (i. v.) injection of 0.025 mg of a solution of octreotide. In a second experiment, release kinetics was studied in eight rabbits for 49 days after an i.m. injection of 5 mg/kg of octreotide-LAR. Concentrations were determined by radioimmunoassay. After i.v. injection of octreotide, one- and two-compartment models were compared for each rabbit. A typical disposition profile was computed using the mean parameters. After i.m. injection of octreotide-LAR, deconvolution was performed using the point-area method. Individual absorption profiles were characterised using natural splines. The number of breakpoints was selected using the generalised cross-validation criterion. The two compartment model was selected based on the i.v. study. After i.m. administration, octreotide exhibited a triphasic absorption profile, with large interindividual variability. A transient peak followed the initial burst phase. The third phase covered 85% of total drug released. The approach allows a model-independent description of the in vivo absorption profile of octreotide-LAR.
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PMID:Nonparametric analysis of the absorption profile of octreotide in rabbits from long-acting release formulation OncoLAR. 1033 54

Somatostatin has represented a significant breakthrough in the treatment of patients with hormonally-acting, neuroendocrine gastroenteropancreatic neoplasms, even if its short half-life made it impractical in the clinic. In recent years, new long-acting formulations have been developed from the native peptide. The long-lasting formulation of the somatostatin analogue octreotide (octreotide-LAR) can be administered once-monthly and has been shown to provide similar efficacy to subcutaneous octreotide administered three times a day in the control of flushing and diarrhoea associated with the carcinoid syndrome. Another-long acting somatostatin analogue, lanreotide, is available in a slow-release form, lanreotide-SR. In a multicentre 6-month trial on carcinoid tumour patients, 30 mg lanreotide-SR were administered intramuscularly every 14 days, obtaining the control of symptoms in the majority of subjects. Thus, both octreotide-LAR administered monthly, and lanreotide-SR administered every 10-14 days, have been shown to be an effective tool in the treatment of carcinoid tumours, providing, in addition, a substantial improvement in patient compliance.
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PMID:Long-acting formulations of somatostatin analogues. 1060 34

The peroxisome proliferator ciprofibrate induces hypergastrinemia and as a consequence, enterochromaffin-like (ECL) cell hyperplasia. The mechanism for the gastrin cell stimulation is unknown. The somatostatin analog octreotide LAR (long-acting release) was used to see if the stimulating effects of ciprofibrate could be attenuated. Female Fischer rats were dosed with ciprofibrate (50 mg/kg body weight per day) alone or combined with octreotide LAR (10 mg/30 days) for 60 days. Plasma gastrin and histamine, gastric endocrine cell densities and mRNA abundances were measured. Ciprofibrate increased gastrin mRNA abundance (P<0.05), gastrin cell number (P<0. 001) and cell area (P<0.01), and induced hypergastrinemia (P<0.001). These rats had profound ECL cell hyperplasia, confirmed by an increase in chromogranin A (CgA) and histidine decarboxylase (HDC) mRNA, density of neuroendocrine and ECL cells and plasma histamine levels (all P<0.001). Octreotide LAR did not affect ciprofibrate stimulation of gastrin cells, but all parameters of ECL cell hyperplasia were reduced (P<0.001). Octreotide LAR also significantly inhibited basal ECL cell function and growth. Ciprofibrate stimulates gastrin cell activity by a mechanism unaffected by octreotide, but octreotide does inhibit basal and gastrin-stimulated ECL cell function and growth.
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PMID:Octreotide inhibits the enterochromaffin-like cell but not peroxisome proliferator-induced hypergastrinemia. 1091 23

Current evidence suggests that the new depot somatostatin analogues octreotide LAR and lanreotide are at least as efficacious in the suppression of growth hormone (GH) and insulin-like growth factor I (IGF-I) secretion as subcutaneous octreotide. An ongoing study is examining the GH and IGF-I responses to these depot formulations in individual patients. The preliminary results indicate that there is great variation between individuals in their responses to either drug; however, for the majority of patients, the GH and IGF-I responses to octreotide LAR are as well maintained at 6 weeks after the last injection as at 4 weeks, which is the manufacturer's recommended dosage interval. These results suggest that care needs to be taken to optimize the dose and dosage interval for each patient when commencing depot somatostatin analogue therapy.
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PMID:The use of long-acting somatostatin analogues in acromegaly. 1098 65

Cardiovascular disease is the most severe complication of acromegaly accounting for the increased mortality of these patients. Recently, the slow-release form of octreotide (OCT; Sandostatin LAR, OCT-LAR), for im injection every 28 days, was reported to induce suppression of GH levels below 7.5 mU/L (2.5 microg/L) in 39-75% of patients, and normalization of insulin-like growth factor (IGF)-I levels for age in 64-88% of patients, with an excellent patients' compliance. The aim of the present study was to investigate the early effect of OCT-LAR treatment on the left ventricular (LV) structure and performance in 15 somatostatin analog-naive patients with acromegaly (GH, 94.8 +/- 24.9 mU/L; IGF-I, 757.9 +/- 66.6 microg/L), focusing on the early effect of GH and IGF-I suppression on the heart. Cardiac structure was investigated by echocardiography, whereas LV performance was investigated by gated-blood-pool scintigraphy, before and after 3 and 6 months of treatment with OCT-LAR. OCT-LAR was initially administered im, at a dose of 20 mg every 28 days, for 3 months. In six patients, the dose was then increased to 30 mg every 28 days to achieve disease control, which was considered when fasting and/or glucose-suppressed GH values were below 7.5 and 3.0 mU/L, respectively, together with IGF-I values within the normal range for age. The treatment with OCT-LAR for 6 months induced a significant decrease of GH (to 12.9 +/- 3.0 mU/L) and IGF-I levels (to 340.3 +/- 40.2 microg/L) in all 15 patients. After 6 months of treatment, the percent IGF-I suppression was 52.8 +/- 4.4%, and serum GH/IGF-I levels were normalized in 9 patients. A significant decrease of LV mass index (LVMi), interventricular septum thickness, and LV posterior wall thickness was observed in all 15 patients after 3 and 6 months of OCT-LAR treatment: LVMi was decreased by 19.1 +/- 2.0% without any difference in patients with (19.9 +/- 2.7%) or without disease control (17.8 +/- 3.3%). Among the 11 patients with LV hypertrophy, 6 normalized their LVMi after treatment. At study entry, an inadequate LV ejection fraction (LVEF) at rest (<50%) was found in 5 patients (33.3%), whereas an impaired response of LVEF at peak exercise (<5% increase of basal value) was found in 9 patients (60%). A significant increase in LVEF, both at rest (from 51.6 +/- 2.6 to 58.1 +/- 1.7%, P < 0.01) and at peak exercise (from 51.6 +/- 2.3 to 60.2 +/- 2.4%, P < 0.001) was found in patients with (as compared with those without) disease control (from 55.2 +/- 3.8 to 58.0 +/- 4% and from 61.8 +/- 4.6 to 61.8 +/- 3.4%, respectively). Among the 5 patients with inadequate LVEF at rest, all but 1 regained a normal LVEF after 6 months of treatment; whereas, among the 9 patients with an impaired response of the LVEF at peak exercise, 3 patients normalized, 4 improved, and 2 impaired their responses after treatment. The percent of IGF-I suppression was significantly correlated with the percent increase of resting LVEF (r = 0.644, P < 0.01). Exercise duration (from 6.0 +/- 0.7 to 7.3 +/- 0.7 min) and capacity (from 69.0 +/- 8.2 to 80 +/- 7.8 watts) were increased in the 15 patients considered as a whole, but the improvement in the exercise response was significant only in patients with disease control (P < 0.01 and P < 0.05, respectively) who also had an increase in the peak ejection rate (P = 0.03). No change in hemodynamic parameters, either at rest or at peak exercise, was found after treatment with OCT-LAR in the 15 patients. In conclusion, the results of the present study demonstrate that OCT-LAR im injections every 28 days induces a sustained suppression of GH levels and IGF-I levels in all acromegalic patients, allowing achievement of disease control in 60% of patients after 6 months of treatment. The sustained suppression of IGF-I levels was followed by a significant reduction of LVMi in all patients already after 3 months of treatment, with recovery of LV hypertrophy in 6 of 11 patients. (ABSTRACT TRUN
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PMID:Cardiovascular effects of depot long-acting somatostatin analog Sandostatin LAR in acromegaly. 1099 98


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