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Diabetes Obes Metab. 2016 Jan;18(1):34-9. doi: 10.1111/dom.12571. Epub 2015 Oct 14.

Pharmacokinetics and pharmacodynamics of various glucagon dosages at different blood glucose levels.

Author information

1
Inreda Diabetic BV, Goor, The Netherlands.
2
Department of Endocrinology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
3
Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany.
4
Herzzentrum Wuppertal, Universität Witten-Herdecke, Witten, Germany.

Abstract

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.

KEYWORDS:

glucagon; pharmacodynamics; pharmacokinetics; type 1 diabetes

PMID:
26343550
DOI:
10.1111/dom.12571
[Indexed for MEDLINE]

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