Pharmacokinetics and Bioavailability of Injected Glucagon: Differences Between Intramuscular, Subcutaneous, and Intravenous Administration

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Abstract
Pharmacokinetics and bioavailability of 1 mg glucagon injected intramuscularly (i.m.), subcutaneously (s.c.), or intravenously (i. v.) were studied in 6 nondiabetic men rendered hypoglycemic by s.c. injection of 10 U regular insulin. At 90 min after the insulin injection, when blood glucose levels had fallen to a mean of 49 mg/dl, glucagon was administered. Ten minutes later plasma glucagon levels had risen from a mean of 246 to 3233 pg/ml (s.c. experiment) and from 250 to 2638 pg/ml (i.m. experiment). Accordingly, there was no difference in blood glucose behavior whether glucagon was injected s.c. or i.m. In the i.v. experiment, plasma glucagon levels were significantly higher during the first 15 min after the glucagon injection when compared with the other experiments. The initially high levels of plasma glucagon after i.v. administration were associated with a steeper rise of glycemia during the first 5 min after glucagon injection; the maximal increase of blood glucose was, however, not different when compared with the s.c. or i.m. route of glucagon administration. Thus, in case of severe hypoglycemia, therapeutically administered glucagon will be most efficient when injected i.v., but there is no difference between the i.m. and s.c. routes of administration with regard to the efficacy to increase blood glucose levels.

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