Pharmacokinetics and pharmacodynamics of various glucagon dosages at different blood glucose levels.
OBJECTIVE
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.
Inreda Diabetic BV, Goor, The Netherlands.|Department of Endocrinology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
H
H
Blauw
Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany.
I
I
Wendl
Department of Endocrinology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
J H
JH
DeVries
Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany.
T
T
Heise
Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany.|Herzzentrum Wuppertal, Universität Witten-Herdecke, Witten, Germany.
T
T
Jax
D000328:Adult; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D005934:Glucagon / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D005765:Gastrointestinal Agents; D007004:Hypoglycemic Agents; D005934:Glucagon
glucagon; pharmacodynamics; pharmacokinetics; type 1 diabetes