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Pharmacokinetics and Pharmacodynamics of Inhaled GLP‐1 (MKC253): Proof‐of‐Concept Studies in Healthy Normal Volunteers and in Patients With Type 2 Diabetes
Author(s) -
Marino M T,
Costello D,
Baughman R,
Boss A,
Cassidy J,
Damico C,
Marle S,
Vliet A,
Richardson P C
Publication year - 2010
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2010.85
Subject(s) - pharmacokinetics , pharmacodynamics , glucagon like peptide 1 , medicine , diabetes mellitus , type 2 diabetes , insulin , inhalation , pharmacology , endocrinology , glucagon , anesthesia
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. Clinical Pharmacology & Therapeutics (2010) 88 2, 243–250. doi: 10.1038/clpt.2010.85