Oral administration of the growth hormone secretagogue NN703 in adult patients with growth hormone deficiency

Svensson, Johan; Monson, John P.; Vetter, T.; Hansen, T. K.; Savine, Richard; Kann, Peter Herbert; Bex, Marie; Reincke, Martín; Hagen, Claus; Beckers, Albert; Ilondo, M M; Zdravković, Milan; Bengtsson, Bengt‐Åke; Korbonits, Márta

doi:10.1046/j.1365-2265.2003.01754.x

Cited by 20 publications

(16 citation statements)

References 48 publications

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“…Clinical trials have already been performed to assess the utility of GHS for the treatment of short stature (24), GH deficiency (24,25), obesity (26) and catabolic conditions (27). However, only preliminary studies have been performed to assess the possible benefits of ghrelin administration to humans (12-18, 28 -31).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects

Akamizu

Takaya²,

Irako³

et al. 2004

European Journal of Endocrinology

200

119

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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, placebocontrolled 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 mg/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 mg/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.European Journal of Endocrinology 150 447-455

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, safety, and endocrine and appetite effects of ghrelin administration in young healthy subjects

Akamizu

Takaya²,

Irako³

et al. 2004

European Journal of Endocrinology

200

119

View full text Add to dashboard Cite

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“…Clinical trials have already been performed to assess the utility of GHS for the treatment of short stature [19], GH deficiency [19,20], obesity [21] and catabolic conditions [22]. Several preliminary studies have also been performed to assess the possible benefits of ghrelin administration to humans [9][10][11][12][13][14][15][23][24][25][26].…”

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confidence: 99%

Translational Research on the Clinical Applications of Ghrelin

Akamizu

Kangawa

2006

Endocr J

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“…O MK-0677 também foi utilizado em crianças com deficiência de GH por oito dias, e também houve aumento significativo de GH, IGF-1 e IGFBP-3 em algumas crianças (50). Mais recentemente outro agonista oral dos GHS, o NN703, foi utilizado em 83 pacientes adultos com deficiência de GH durante seis dias, e apenas 11% atingiram pico de GH maior que 5 µg/L após sua administração (51). A administração intranasal de GHRP-2, outro GHS, em crianças com baixa estatura (50% com deficiência de GH e 50% com baixa estatura idiopática) durante três meses levou a pequeno aumento, mas significante, da velocidade de crescimento, sem mudanças nas concentrações de IGF-1 e de IGFBP-3 ou nos picos de GH (52).…”

Section: Ghrelina/ghs: Modulação Gh/uso Terapêuticounclassified

Ghrelina e secretagogos do hormônio de crescimento (GHS): modulação da secreção do hormônio de crescimento e perspectivas terapêuticas

Correa‐Silva

Lengyel

2008

Arq Bras Endocrinol Metab

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RESUMOA secreção do hormônio de crescimento (gH) é modulada pelo hormônio liberador de hormônio de crescimento (gHrH) e pela somatostatina. na últi-ma década foi descoberto um terceiro mecanismo de controle, envolvendo os secretagogos de gH (gHs). A ghrelina, o ligante endógeno do receptor dos gHs, é um peptídeo acilado produzido no estômago, que também é sintetizado no hipotálamo. este peptídeo é capaz de liberar gH, além de aumentar a ingesta alimentar. A ghrelina endógena parece amplificar o padrão básico de secreção de gH, ampliando a resposta do somatotrofo ao gHrH, estimulando múltiplas vias intracelulares interdependentes. entretanto, seu local de atuação predominante é o hipotálamo. neste trabalho, será apresentada revisão sobre a descoberta da ghrelina, os mecanismos de ação e o possível papel fisiológico dos gHs e da ghrelina na secreção de gH e, finalmente, as possíveis aplicações terapêuticas destes compostos. ABSTRAcT Ghrelin and Growth Hormone Secretagogues (GHS): Modulation of GrowthHormone Secretion and Therapeutic Applications. growth hormone-releasing hormone (gHrH) and somatostatin modulate growth hormone (gH) secretion. A third mechanism was discovered in the last decade, involving the action of growth hormone secretagogues (gHs). ghrelin, the endogenous ligand of the gHs-receptor, is an acylated peptide mainly produced by the stomach, but also synthesized in the hypothalamus. this compound increases both gH release and food intake. endogenous ghrelin might amplify the basic pattern of gH secretion, optimizing somatotroph responsiveness to gHrH, activating multiple interdependent intracellular pathways. However, its main site of action is the hypothalamus. in the current paper it is reviewed the available data on the discovery of this peptide, the mechanisms of action and possible physiological roles of the gHs and ghrelin on gH secretion, and finally, the possible therapeutic applications of these compounds.

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Oral administration of the growth hormone secretagogue NN703 in adult patients with growth hormone deficiency

Cited by 20 publications

References 48 publications

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

Translational Research on the Clinical Applications of Ghrelin

Ghrelina e secretagogos do hormônio de crescimento (GHS): modulação da secreção do hormônio de crescimento e perspectivas terapêuticas

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