title: Glucagon-like peptide-1(7-37) has a larger volume of distribution than glucagon-like peptide-1(7-36)amide in dogs and is degraded more quickly in vitro by dog plasma.
abstract: The pharmacokinetic properties of glucagon-like peptide-1(7-36)amide (GLP-1(7-37) were compared. Four beagle dogs received on 4 separate occasions s.c. bolus doses of 50 micrograms/kg, and 2 min i.v. infusions of 50 micrograms/kg of each peptide. The plasma immunoreactivity of GLP-1 (P-GLP-1-IR) was measured by a sandwich enzyme-linked immunosorbent assay (ELISA). After i.v. infusion, the plasma half-life in the first-phase was 2.1 +/- 0.1 and 2.4 +/- 0.3 min, in the final-phase 68 +/- 6 and 81 +/- 3 min, the total plasma clearance 25 +/- 3 and 22 +/- 4 ml/kg.min, the volume of distribution at steady state 0.16 +/- 0.02 and 0.84 +/- 0.24 l/kg, and the mean residence time 6.2 +/- 0.3 and 36 +/- 5 min for GLP-1(7-36)amide and GLP-1(7-37), respectively. After s.c. administration, the maximum plasma concentration was reached after 15 +/- 5 and 19 +/- 4 min and the absolute bioavailability was 48 +/- 7 and 49 +/- 13% for GLP-1(7-36)amide and GLP-1(7-37), respectively. P-GLP-1-IR, measured by a radioimmunoassay (RIA), was considerably higher than when measured by ELISA. This discrepancy was due to cross-reactivity with metabolites of the parent peptide. The plasma degradation was studied in vitro in dog plasma at 37 degrees C, and the half-lives were found to be 61 +/- 9 and 132 +/- 16 min for GLP-1(7-36)amide and GLP-1(7-37), respectively (n = 6). Bacitracin inhibited the degradation of both peptides.
authors.affiliation: Novo Nordisk, Diabetes Discovery, Bagsvaerd, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Pridal
authors.forename: C F
authors.initials: CF
authors.lastname: Deacon
authors.forename: O
authors.initials: O
authors.lastname: Kirk
authors.forename: J V
authors.initials: JV
authors.lastname: Christensen
authors.forename: R D
authors.initials: RD
authors.lastname: Carr
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
mesh_terms: D000818:Animals; D004285:Dogs; D005260:Female; D005768:Gastrointestinal Hormones / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D052216:Glucagon-Like Peptide 1; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D010455:Peptides / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D005768:Gastrointestinal Hormones; D010455:Peptides; D052216:Glucagon-Like Peptide 1