H Blauw1,2, I Wendl3, J H DeVries2, T Heise3, T Jax3,4. 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.
RCT Entities:
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.
Authors: Marco Infante; David A Baidal; Michael R Rickels; Andrea Fabbri; Jay S Skyler; Rodolfo Alejandro; Camillo Ricordi Journal: Artif Organs Date: 2021-07-15 Impact factor: 2.663
Authors: Ingrid Anna Teigen; Marte Kierulf Åm; Sven Magnus Carlsen; Sverre Christian Christiansen Journal: Eur J Drug Metab Pharmacokinet Date: 2021-06-07 Impact factor: 2.441