| Pharmacokinetics and pharmacodynamics of inhaled GLP-1 (MKC253): proof-of-concept studies in healthy normal volunteers and in patients with type 2 diabetes. | |
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MedLine Citation:
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PMID: 20592721 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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MKC253 is glucagon-like peptide 1 (GLP-1, 7-36 amide) adsorbed onto Technosphere microparticles for oral inhalation. The pharmacokinetics of inhaled GLP-1 and the pharmacokinetic-pharmacodynamic (PK-PD) relationship between inhaled GLP-1 and insulin were analyzed in two trials, one in healthy normal volunteers and the other in patients with type 2 diabetes. Inhaled GLP-1 was absorbed quickly, with peak concentrations occurring within 5 min, and levels returned to baseline within 30 min. Inhaled GLP-1 appeared to produce plasma levels of GLP-1 comparable to those of parenteral administration and sufficient to induce insulin secretion resulting in attenuation of postmeal glucose excursions in subjects with type 2 diabetes. An E(max) (maximum effect) model described the relationship between GLP-1 concentration and insulin release. The variability in the E(max) may be due to differences in baseline glucose levels, differences resulting from genetic polymorphisms in GLP-1 receptors (GLP-1Rs), or the stage of diabetes of the patient. |
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Authors:
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M T Marino; D Costello; R Baughman; A Boss; J Cassidy; C Damico; S van Marle; A van Vliet; P C Richardson |
Publication Detail:
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Type: Clinical Trial, Phase I; Journal Article Date: 2010-06-30 |
Journal Detail:
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Title: Clinical pharmacology and therapeutics Volume: 88 ISSN: 1532-6535 ISO Abbreviation: Clin. Pharmacol. Ther. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-21 Completed Date: 2010-08-12 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372741 Medline TA: Clin Pharmacol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 243-50 Citation Subset: AIM; IM |
Affiliation:
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MannKind Corporation, Paramus, New Jersey, USA. mmarino@mannkindcorp.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Inhalation Adult Aged Blood Glucose / metabolism C-Peptide / metabolism Diabetes Mellitus, Type 2 / blood, metabolism* Dose-Response Relationship, Drug Drug Delivery Systems Energy Intake Female Glucagon / blood Glucagon-Like Peptide 1 / administration & dosage, adverse effects, pharmacokinetics* Humans Hypoglycemic Agents / administration & dosage, adverse effects, pharmacokinetics* Insulin / blood Male Middle Aged Peptide Fragments / administration & dosage, adverse effects, pharmacokinetics* |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/C-Peptide; 0/Hypoglycemic Agents; 0/Peptide Fragments; 11061-68-0/Insulin; 119637-73-9/glucagon-like peptide 1 (7-36)amide; 89750-14-1/Glucagon-Like Peptide 1; 9007-92-5/Glucagon |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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