CLINICAL PHARMACOLOGY
Glucagon increases blood glucose concentration and
is used in the treatment of hypoglycemia. Glucagon acts only on liver glycogen,
converting it to glucose.
Glucagon administered
through a parenteral route relaxes smooth muscle of the stomach, duodenum,
small bowel, and colon.
Pharmacokinetics
Glucagon has been studied following intramuscular,
subcutaneous, and intravenous administration in adult volunteers. Administration
of the intravenous glucagon showed dose proportionality of the pharmacokinetics
between 0.25 and 2.0 mg. Calculations from a 1 mg dose showed a small volume
of distribution (mean, 0.25 L/kg) and a moderate clearance (mean, 13.5 mL/min/kg).
The half-life was short, ranging from 8 to 18 minutes.
Maximum plasma concentrations of 7.9 ng/mL were achieved approximately
20 minutes after subcutaneous administration (). With
intramuscular dosing, maximum plasma concentrations of 6.9 ng/mL were attained
approximately 13 minutes after dosing.
see
Figure 1A
Glucagon
is extensively degraded in liver, kidney, and plasma. Urinary excretion of
intact glucagon has not been measured.
Pharmacodynamics
In a study of 25 volunteers, a subcutaneous dose
of 1 mg glucagon resulted in a mean peak glucose concentration of 136 mg/dL
30 minutes after injection (). Similarly, following
intramuscular injection, the mean peak glucose level was 138 mg/dL, which
occurred at 26 minutes after injection. No difference in maximum blood glucose
concentration between animal-sourced and rDNA glucagon was observed after
subcutaneous and intramuscular injection.
see
Figure 1B
Figure 1 Mean (±SE) serum glucagon and blood glucose levels after subcutaneous injection of glucagon (1 mg) in 25 normal volunteers
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