Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects
Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects
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DOI：
10.1530/eje.0.1500447
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发表时间：
2004-04-01
影响因子：
5.8
通讯作者：
Kangawa, K
中科院分区：
文献类型：
--
作者：
Akamizu, T;Takaya, K;Kangawa, K
目的：Ghrelin在生长激素分泌和摄食调节中起重要作用。这些作用使得生长激素释放肽成为治疗生长激素缺乏症、厌食症和恶病质的强有力的候选者。然而，仅进行了初步研究以评估人体中的ghrelin给药。在这项研究中，我们进行了一项双盲，随机，安慰剂对照试验，以调查的药物动力学，安全性，内分泌和食欲的影响ghrelin在年轻的健康volunteers.Design：18名男性志愿者被随机分为三组，每组6名受试者：低剂量和高剂量生长激素释放肽组，接受静脉注射1和5 μ g/kg生长激素释放肽结果：血浆中酰化Ghrelin的消除比总Ghrelin快，消除半衰期（t（1/2））分别为9-13和27-31 min。发生不良反应的受试者数量在三组之间无显著差异，所有不良反应均为一过性且耐受性良好。低剂量和高剂量的生长素释放肽均强烈刺激GH释放（峰值血浆浓度（C（max，0-90）min）：1和5 μ g/kg生长素释放肽分别为124.2 +/- 63.9和153.2 +/- 52.2 ng/ml）。观察到注射后血糖和胰岛素水平的轻微变化。虽然没有统计学意义上的，生长激素释放肽管理往往增加饥饿感的剂量依赖mathematics.Conclusions：这些结果表明，生长激素释放肽是安全的，临床试验可能会开始评估生长激素释放肽的有用性相关的GH分泌和食欲的疾病的治疗。
Objective: It has been demonstrated that ghrelin plays a major role in the regulation of GH secretion and food intake. These actions make ghrelin a strong candidate for the treatment of GH deficiency, anorexia and cachexia. However, only preliminary studies have been performed to assess ghrelin administration in humans. In this study, we have conducted a double-blind, randomized, placebo-controlled trial to investigate the pharmacokinetics, safety, and endocrine and appetite effects of ghrelin in young healthy volunteers.Design: Eighteen male volunteers were randomly assigned into three groups of six subjects: low- and high-dose ghrelin groups, who received intravenous injections of 1 and 5 mug/kg ghrelin (acylated form) respectively, and a placebo group who were injected with mannitol instead of ghrelin.Results: Acylated ghrelin disappeared more rapidly from plasma than total ghrelin, with elimination half life (t(1/2)) of 9-13 and 27-31 min respectively. The number of subjects that experienced adverse effects did not significantly differ among the three groups, and all adverse effects were transient and well tolerated. Both the low and high doses of ghrelin strongly stimulated GH release (peak plasma concentration (C(max,0-90)min): 124.2 +/- 63.9 and 153.2 +/- 52.2 ng/ml for 1 and 5 mug/kg ghrelin respectively). Slight alterations of blood glucose and insulin levels after the injection were observed. Although not statistically significant, ghrelin administration tended to increase hunger sensation in a dose-dependent manner.Conclusions: These results suggest that ghrelin is safe, and that clinical trials may be started to assess the usefulness of ghrelin for the treatment of disorders related to GH secretion and appetite.