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 ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1996-03

AUTHORS

L. Pridal, C. F. Deacon, O. Kirk, J. V. Christensen, R. D. Carr, J. J. Holst

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. More... »

PAGES

51-59

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf03190278

DOI

http://dx.doi.org/10.1007/bf03190278

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1006004995

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/8839678


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