The pharmacokinetics, pharmacodynamics, safety and tolerability following 7 days daily oral treatment with NN703 in healthy male subjects

Zdravković, Milan; Christiansen, Tina; Eliot, Lise; Agersoe, H.; Thomsen, Mikael S.; Falch, John; Søgaard, Birgitte; Ynddal, Lars; Ilondo, M M

doi:10.1054/ghir.2000.0188

Cited by 14 publications

(12 citation statements)

References 19 publications

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“…Another approach to avoid the needle injections has been the development of oral available growth hormone secretagogues, [6][7][8][9] which, however, will be of sure value only in patients with a hypothalamic rather than a pituitary cause of GH deficiency. Despite promising results, none of these products are currently available on the market.…”

confidence: 99%

No Effect of the Novel Antidiabetic Agent Nateglinide on the Pharmacokinetics and Anticoagulant Properties of Warfarin in Healthy Volunteers

Anderson¹,

Shelley²,

Crick³

et al. 2002

The Journal of Clinical Pharma

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The novel hypoglycemic agent nateglinide is pharmacologically distinct from oral hypoglycemic agents such as sulfonylureas and repaglinide. The present study investigated the effects in healthy volunteers of multiple doses of nateglinide on the pharmacokinetics and pharmacodynamics of warfarin. The study comprised a randomized two-group, two-way crossover, open-label design in 12 healthy male subjects. One group of 6 subjects initially received a single oral dose of warfarin 30 mg and then, after a 7- to 14-day washout, received both warfarin and nateglinide (120 mgnateglinide, 10 min before meals for 4 days and a single dose of 30 mg warfarin on the second day). The alternate group of 6 subjects received treatments in the opposite order. Pharmacokinetic profiles were derived from plasma warfarin and nateglinide concentrations. Prothrombin measurements were evaluated in both periods as a measure of warfarin activity. When administered alone or in combination, there were no statistically significant differences in mean warfarin (R- and S-enantiomers) or nateglinide pharmacokinetic parameters. The concurrent administration of nateglinide and warfarin did not affect the maximal change in prothrombin time that follows warfarin administration. In this study, there was no evidence of an effect of coadministration of nateglinide on the pharmacodynamic action of warfarin or any pharmacokinetic interaction between warfarin and nateglinide.

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confidence: 99%

No Effect of the Novel Antidiabetic Agent Nateglinide on the Pharmacokinetics and Anticoagulant Properties of Warfarin in Healthy Volunteers

Anderson¹,

Shelley²,

Crick³

et al. 2002

The Journal of Clinical Pharma

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“…13 Tabimorelin Tabimorelin, one of the first generation GHSs, was derived from ipamorelin by Novo Nordisk. 14 Tabimorelin increased GH release as well as production of insulin-like growth factor-1 (IGF-1) and IGF binding protein 3 (IGFBP-3) with subtle changes in adrenocorticotropic hormone, cortisol, and prolactin in healthy male subjects, 15,16 while only 11% of patients with GHD responding to tabimorelin with a peak GH concentration >5 μg/L. 17 Furthermore, tabimorelin was reported to inhibit CYP3A4, which may lead to unexpected side effects.…”

Section: Examorelinmentioning

confidence: 99%

Growth hormone secretagogues: history, mechanism of action, and clinical development

Ishida

Saitoh

Ebner

et al. 2020

JCSM Rapid Communications

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Growth hormone secretagogues (GHSs) are a generic term to describe compounds that increase growth hormone (GH) release. GHSs include agonists of the growth hormone secretagogue receptor (GHS‐R), whose natural ligand is ghrelin, and agonists of the growth hormone‐releasing hormone (GHRH) receptor, to which the GHRH binds as a native ligand. Several GHSs have been developed with a view to treating or diagnosing of GH deficiency, which causes growth retardation, gastrointestinal dysfunction, and altered body composition, in parallel with extensive research to identify GHRH, GHS‐R, and ghrelin. This review will focus on the research history and the pharmacology of each GHS, which reached randomized clinical trials. Furthermore, we will highlight the publicly disclosed clinical trials regarding GHSs.

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“…Other efficient GHS were synthesised in the 90s and went into clinical trials. The peptidomimetic NN703 8 derived from Ipamorelin 7 was orally bioavailable and dose‐dependently increased GH release and the gain of weight in dogs but was less efficient than MK‐0677 in humans (Scheme )140, 141. Further pharmacomodulation of NN703 8 did not succeed in improving in vivo efficacy142, 143.…”

Section: Ghrelin Analogues and Their Biological Activitymentioning

confidence: 99%

Ghrelin—a novel generation of anti‐obesity drug: design, pharmacomodulation and biological activity of ghrelin analogues

Chollet

Meyer

Beck‐Sickinger

2009

Journal of Peptide Science

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Ghrelin is a unique bioactive peptide with respect to both the structure and its biological function. This 28-amino acid peptide is modified with an n-octanoyl group at serine-3, and accordingly is the only lipidated biologically active peptide hormone known so far. Ghrelin binds to the so-called ghrelin or GHS receptor, a member of the class A of G-protein coupled receptors, which leads to Ca(2+) release intracellularly due to the activation of the Gq-system. Interestingly, the ghrelin receptor shows a significant constitutive activity which means that in addition to agonists and antagonists, inverse agonists play an important role in receptor modulation. In this review, the major activities of ghrelin are summarized with a strong focus on the regulation of food intake. So far reported agonists, antagonists and inverse agonists are shown and structure activitiy relationships are discussed. Furthermore, the application of ghrelin ligands as novel anti-obesity drugs is outlined and the state of the art in this field is summarized.

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The pharmacokinetics, pharmacodynamics, safety and tolerability following 7 days daily oral treatment with NN703 in healthy male subjects

Cited by 14 publications

References 19 publications

No Effect of the Novel Antidiabetic Agent Nateglinide on the Pharmacokinetics and Anticoagulant Properties of Warfarin in Healthy Volunteers

No Effect of the Novel Antidiabetic Agent Nateglinide on the Pharmacokinetics and Anticoagulant Properties of Warfarin in Healthy Volunteers

Growth hormone secretagogues: history, mechanism of action, and clinical development

Ghrelin—a novel generation of anti‐obesity drug: design, pharmacomodulation and biological activity of ghrelin analogues

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