Safety, Pharmacokinetics and Pharmacodynamics of the Recombinant Glucagon(GL-G) on Two Serial Administrations.

Purpose: Giucagon is in wide clinical use (growth hormone secretion test, diagnosis of insulinoma, and pretreatment for radiography or endoscopic examination of the digestive tract etc.). The action time of glucagon in the pretreatment for endoscopy has been confirmed to be about 15 minutes by intravenous administration and about 25 minutes by intramuscular administration. Clinically, however, the examination may be prolonged for various reasons, and additional administration may become necessary. In this study, glucagon was administered twice at an interval of 15 minutes intravenously and 25 minutes intramuscularly, and the pharmacokinetics and changes in the blood glucose and insulin concentrations were investigated. The findings were also evaluated with previously obtained results after a single administration.<BR>Methods: Recombinant glucagon (GL-G) was administered to the healthy volunteers at 1 mg twice at an interval of 15 minutes intravenously (n=6) and 25 minutes intramuscularly (n=6), and the changes in the blood glucagon, insulin, and glucose concentrations after administration were evaluated.<BR>Results: C_max of the blood glucagon concentration did not increase on two serial administrations by the intravenous route, but that after the second administration was about twice the level after the first administration by the intramuscular route (mean±SD, 3645±743 pg/ml after the first administration and 7402±1770 pg/ml after the second administration). The glucagon concentration returned to the level of 15 minutes and 25 minutes after the first intravenous and intramuscular administrations, respectively, [estimated to be the minimum effective concentrations (MEC) for the digestive tract] at about 30 minutes and 70 minutes, after the first administrations.<BR>C_max of the blood glucose concentration was about 1.4 times higher by two serialintravenous administrations and 1.3 times higher by two serial intramuscular administrations than the levels after a single administration, and the decreases in the blood glucoseconcentration 1.5-2 hours after the administration, which are considered to be rebounds, were similar to those observed after a single administration.<BR>Conclusions: 1) The tolerability of two serial administrations of GL-G was satisfactory by both intravenous and intramuscular administrations. 2) From changes in theblood glucagon concentration, the times of suppression of peristalsis of the digestive tracton two serial intravenous and intramuscular administrations were estimated to be abouttwice and three times those on a single administration, respectively. 3) The rebounddecrease in the blood glucose concentration was similar between single and two serialadministrations.