Premium
Pharmacokinetics and pharmacodynamics of various glucagon dosages at different blood glucose levels
Author(s) -
Blauw H.,
Wendl I.,
DeVries J. H.,
Heise T.,
Jax T.
Publication year - 2016
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12571
Subject(s) - glucagon , pharmacodynamics , pharmacokinetics , medicine , endocrinology , dose , diabetes mellitus , hypoglycemia , insulin
Aims To evaluate the pharmacokinetics and pharmacodynamics of different doses of glucagon administered subcutaneously (s.c.) at different blood glucose levels. Methods This study was an open‐label, randomized, three‐period, cross‐over experiment in 6 patients with type 1 diabetes. During each of the three periods, different blood glucose levels were established in four consecutive steps (8, 6, 4 and 2.8 mmol/l) and glucagon was given at each blood glucose level in doses from 0.11 to 0.44 mg and 0.33, 0.66 and 1 mg at the lowest glucose concentration. Results Maximum glucagon concentration and area under the curve increased with increasing glucagon dose. Maximum glucagon concentration was reached after 10–20 min. Glucagon raised blood glucose in a dose‐dependent manner at different baseline blood glucose levels. The median glucose excursion ranged from 2.6 to 6.2 mmol/l. Time to maximum glucose concentration was dose‐dependent for the glucagon doses at 2.8 mmol/l, with median values from 40 to 80 min. Conclusions Glucagon administered s.c. produces a stable pharmacokinetic and pharmacodynamic response at lower doses than the usual rescue dose and across a range of hypo‐ to hyperglycaemic blood glucose levels. This supports the use of small glucagon doses in the artificial pancreas to correct and prevent hypoglycaemia.