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生长抑素类似物SMS 201-995在肢端肥大症中的应用:对生长激素的长效、优先抑制作用,而非对胰腺激素的抑制作用。

The somatostatin analogue SMS 201-995 in acromegaly: prolonged, preferential suppression of growth hormone but not pancreatic hormones.

作者信息

George S R, Hegele R A, Burrow G N

机构信息

Department of Medicine, Toronto General Hospital, University of Toronto, Ontario.

出版信息

Clin Invest Med. 1987 Jul;10(4):309-15.

PMID:2888554
Abstract

The treatment of acromegaly is not optimal at present, since many patients have continued growth hormone hypersecretion. We report the acute effects of a cyclic octapeptide analogue of somatostatin, SMS 201-995 (Sandoz) in 9 nondiabetic, acromegalic patients between the ages of 30 and 74. We report potent and prolonged dose-dependent effects to suppress growth hormone secretion. A single 50 micrograms dose of SMS 201-995 inhibited growth hormone concentration rapidly within 15 minutes, with maximal effect in 75 minutes. Maximal inhibition was of the order of 80%, with absolute concentrations under 2 micrograms/L for about 6 hours in 5 of 7 patients. Growth hormone concentrations remained significantly suppressed below placebo control for up to 24 hours after a single dose of SMS 201-995, but the inhibitory effects on insulin and C-peptide concentrations were limited to 2 hours. The effects on glucagon secretion were minimal, and also evident for only 2 hours. Mild transient postprandial elevations of plasma glucose and FFA were documented. No adverse effects were noted; routine hematology, biochemistry, and vital signs were not altered. Thus SMS 201-995, with preferential effects at the pituitary somatotroph, holds considerable promise as an attractive and viable alternative for treatment of acromegaly.

摘要

目前肢端肥大症的治疗并不理想,因为许多患者的生长激素仍持续分泌过多。我们报告了一种生长抑素环八肽类似物SMS 201-995(山德士公司生产)对9名年龄在30至74岁之间的非糖尿病肢端肥大症患者的急性影响。我们报告了其抑制生长激素分泌的强效且持久的剂量依赖性效应。单次给予50微克剂量的SMS 201-995可在15分钟内迅速抑制生长激素浓度,75分钟时达到最大效应。最大抑制程度约为80%,7名患者中有5名患者的生长激素绝对浓度在2微克/升以下持续约6小时。单次给予SMS 201-995后,生长激素浓度在长达24小时内仍显著低于安慰剂对照组,但对胰岛素和C肽浓度的抑制作用仅持续2小时。对胰高血糖素分泌的影响极小,且也仅持续2小时。记录到餐后血浆葡萄糖和游离脂肪酸有轻度短暂升高。未观察到不良反应;常规血液学、生化指标及生命体征均未改变。因此,SMS 201-995对垂体生长激素细胞有优先作用,作为肢端肥大症治疗的一种有吸引力且可行的替代方法具有很大的前景。

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