Comparison of half-disappearance times, distribution volumes and metabolic clearance rates of exogenous glucagon-like peptide 1 and glucagon in rats.

ABSTRACT

The pharmacokinetics of glucagon-like peptide-1 (GLP-1) in vivo after bolus and continuous i.v. administrations of the peptide were compared with those of glucagon in rats. The half-disappearance time (t1/2) distribution volume (Vd) and metabolic clearance rate (MCR) of GLP-1 given as a bolus injection and by constant infusion, were, respectively, as follows t1/2 (min), 47.7 +/- 14.5 and 39.5 +/- 15.5 (mean +/- S.D.); Vd (ml), 903.8 +/- 62.4 and 516.3 +/- 92.1 and MCR (ml kg-1 min-1), 27.4 +/- 10.8 and 18.6 +/- 8.6. These values differed significantly from the respective values for glucagon (t1/2, 3.3 +/- 0.6 and 5.8 +/- 1.0; Vd, 206.5 +/- 25.9 and 240.0 +/- 76.1; and MCR, 83.1 +/- 8.2 and 46.7 +/- 13.3). These findings demonstrate that GLP-1 is degraded more slowly than glucagon in vivo.