In vivo dynamic distribution of 131I-glucagon-like peptide-1 (7-36) amide in the rat studied by gamma camera.
The in vivo distribution of glucagon-like peptide-1 (7-36) amide (GLP-1) was studied in a rat model using radiolabeled GLP-1 (131I-GLP-1) depicted by a gamma-camera. The dynamic scan showed a rapid clearance from the blood circulation after an intravenous (i.v.) injection of 131I-GLP-1. After 10 min, the major part of the radioactivity was accumulated in the kidneys, whereas about 9% (of the blood value) was found in the brain. The pharmacokinetic study using 125I-GLP-1 demonstrated a rapid elimination from plasma, with a half-life of 3.3 +/- 0.6 min, a clearance of 117 +/- 15 mL/min, and a distribution volume of 557 +/- 61 mL. The elimination half-lives for the intact 125I-GLP-1 in lungs and kidneys were determined to 3.7 and 3.9 min, respectively. The metabolite GLP-1 (9-36) amide was followed in blood, lung, and kidney. All other organs assumed to contain low molecular weight fragments of GLP-1. The present study suggest that GLP-1 and/or its labeled metabolites cross the blood-brain barrier. Also the kidney plays an essential role in GLP-1 elimination after an i.v. administration, which can be of clinical interest especially in patients with kidney insufficiency who are treated with GLP-1.
Hassan
M
M
Karolinska Pharmacy, Stockholm, Sweden. hassan@algonet.se
Eskilsson
A
A
Nilsson
C
C
Jonsson
C
C
Jacobsson
H
H
Refai
E
E
Larsson
S
S
Efendic
S
S
D000818:Animals; D001921:Brain / Q000378:metabolism; D015902:Gamma Cameras; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D007457:Iodine Radioisotopes; D008297:Male; D008657:Metabolic Clearance Rate; D010446:Peptide Fragments / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D010446:Peptide Fragments; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon