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- Title
Pharmacokinetics and Pharmacodynamics of Inhaled GLP-1 (MKC253): Proof-of-Concept Studies in Healthy Normal Volunteers and in Patients With Type 2 Diabetes.
- Authors
Marino, M. T.; Costello, D.; Baughman, R.; Boss, A.; Cassidy, J.; Damico, C.; van Marle, S.; van Vliet, A.; Richardson, P. C.
- Abstract
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 Emax (maximum effect) model described the relationship between GLP-1 concentration and insulin release. The variability in the Emax 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.
- Subjects
GLUCAGON-like peptide 1; PHARMACOKINETICS; PHARMACODYNAMICS; INSULIN; DIABETES; PATIENTS; GENETIC polymorphisms
- Publication
Clinical Pharmacology & Therapeutics, 2010, Vol 88, Issue 2, p243
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/clpt.2010.85