P D Home1, L Barriocanal, A Lindholm. 1. Human Diabetes and Metabolism Research Centre, The Medical School, Newcastle upon Tyne, UK. Philip.Home@newcastle.ac.uk
Abstract
OBJECTIVE: The pharmacokinetics of a new insulin analogue, insulin aspart, were compared with unmodified human insulin in a double-blind crossover study of 25 fasting healthy men following a single subcutaneous dose. METHODS: Either insulin aspart or human insulin, 0.1 U x kg-body-weight(-1), was injected subcutaneously and followed by determination of 8-h profiles of serum insulin and plasma glucose concentrations. RESULTS: The absorption of insulin aspart was, on average, more than twice as fast and reached levels more than twice as high compared with human insulin [tmax(ins) of 52 (23) vs 145 (93) min, P < 0.0001; and Cmax(ins) of 41 (11) vs 18 (4) mU x l(-1), P < 0.0001; mean with (SD)]. However, total bioavailability did not differ between the insulins, and thus the mean residence time was significantly shorter for insulin aspart [MRT(ins) of 149 (26) vs 217 (30) min, P < 0.0001]. Plasma glucose (PG) fell more than twice as rapidly [tmin(PG) of 94 (45) vs 226 (120) min, P < 0.0001], to a greater extent [Cmin(PG) 2.1 (0.6) vs 1.4 (0.4) mmol x l(-1), P < 0.0001], and for a shorter duration with insulin aspart than with human insulin. CONCLUSION: With improved subcutaneous absorption characteristics, the insulin aspart concentration-time profile resembles physiological meal-stimulated insulin release more closely than that of unmodified human insulin. This significantly alters the pharmacodynamic response in an advantageous manner in the meal-related treatment of diabetes mellitus.
RCT Entities:
OBJECTIVE: The pharmacokinetics of a new insulin analogue, insulinaspart, were compared with unmodified humaninsulin in a double-blind crossover study of 25 fasting healthy men following a single subcutaneous dose. METHODS: Either insulinaspart or humaninsulin, 0.1 U x kg-body-weight(-1), was injected subcutaneously and followed by determination of 8-h profiles of serum insulin and plasma glucose concentrations. RESULTS: The absorption of insulinaspart was, on average, more than twice as fast and reached levels more than twice as high compared with humaninsulin [tmax(ins) of 52 (23) vs 145 (93) min, P < 0.0001; and Cmax(ins) of 41 (11) vs 18 (4) mU x l(-1), P < 0.0001; mean with (SD)]. However, total bioavailability did not differ between the insulins, and thus the mean residence time was significantly shorter for insulinaspart [MRT(ins) of 149 (26) vs 217 (30) min, P < 0.0001]. Plasma glucose (PG) fell more than twice as rapidly [tmin(PG) of 94 (45) vs 226 (120) min, P < 0.0001], to a greater extent [Cmin(PG) 2.1 (0.6) vs 1.4 (0.4) mmol x l(-1), P < 0.0001], and for a shorter duration with insulinaspart than with humaninsulin. CONCLUSION: With improved subcutaneous absorption characteristics, the insulinaspart concentration-time profile resembles physiological meal-stimulated insulin release more closely than that of unmodified humaninsulin. This significantly alters the pharmacodynamic response in an advantageous manner in the meal-related treatment of diabetes mellitus.
Authors: Lydia A Jakobsen; Anne Jensen; Lars E Larsen; Morten R Sørensen; Hans Christian Hoeck; Lars Arendt-Nielsen; Parisa Gazerani Journal: Int J Physiol Pathophysiol Pharmacol Date: 2011-11-15
Authors: Erin J Mansell; Signe Schmidt; Paul D Docherty; Kirsten Nørgaard; John B Jørgensen; Henrik Madsen Journal: J Pharmacokinet Pharmacodyn Date: 2017-08-22 Impact factor: 2.745