| Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of JNJ-38431055, a Novel GPR119 Receptor Agonist and Potential Antidiabetes Agent, in Healthy Male Subjects. | |
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MedLine Citation:
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PMID: 21975348 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The incidence of type 2 diabetes mellitus is increasing worldwide. Several G-protein-coupled receptor agonists are being studied for their efficacy as antidiabetes agents. JNJ-38431055 is a novel, potent, and orally available selective agonist of the glucose-dependent insulinotropic (GPR119) receptor. Double-blind, randomized, placebo-controlled studies were conducted to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of JNJ-38431055 (2.5-800 mg) in healthy male volunteers. The systemic exposure of JNJ-38431055 in plasma increased in proportion to the dose and was not influenced by coadministration of food. The terminal elimination half-life was ~13 h when administered as an oral suspension formulation. JNJ-38431055 was well tolerated and was not associated with hypoglycemia. As compared with placebo, single-dose oral JNJ-38431055 increased postmeal plasma glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide YY (PYY) concentrations but did not significantly decrease glucose excursion or increase insulin secretion. However, in a graded glucose infusion study, JNJ-38431055 was shown to induce a higher insulin secretion rate (ISR) relative to placebo at elevated plasma glucose levels. These studies provide evidence for the potential efficacy of JNJ-38431055 as an antidiabetes agent in humans. |
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Authors:
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L B Katz; J J Gambale; P L Rothenberg; S R Vanapalli; N Vaccaro; L Xi; D C Polidori; E Vets; T C Sarich; P P Stein |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-05 |
Journal Detail:
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Title: Clinical pharmacology and therapeutics Volume: - ISSN: 1532-6535 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372741 Medline TA: Clin Pharmacol Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Spring House, Pennsylvania, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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