Exp Clin Endocrinol Diabetes 2005; 113(5): 292-297
DOI: 10.1055/s-2005-865637
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

A Comparison of the Steady-State Pharmacokinetics and Pharmacodynamics of a Novel Rapid-Acting Insulin Analog, Insulin Glulisine, and Regular Human Insulin in Healthy Volunteers Using the Euglycemic Clamp Technique[1]

R. H. A. Becker1 , A. D. Frick1 , F. Burger2 , H. Scholtz2 , J. H. Potgieter2
  • 1Aventis Pharma Deutschland GmbH, Industriepark Höchst, 65926 Frankfurt am Main, Germany
  • 2FARMOVS PAREXEL (Pty) Ltd, Private Bag X09, Brandhof 9324, Bloemfontein, South Africa
Further Information

Publication History

Received: August 10, 2004 First decision: August 28, 2004

Accepted: April 11, 2005

Publication Date:
30 May 2005 (online)

Abstract

Insulin glulisine is a new rapid-acting insulin analog. The aim of this study was to assess the glucodynamic efficacy of insulin glulisine compared with regular human insulin (RHI) using a manual euglycemic clamp technique. Steady-state pharmacokinetics of insulin glulisine, and its cardiac safety (ECG) and tolerability after intravenous administration, were also determined. This was a single center, randomized, open-label, two-way crossover study in healthy male subjects (n = 16). At the treatment visits subjects received an intravenous infusion of the study drug at a rate of 0.8 mU kg-1 · min-1 for 2 hours. Individual baseline glucose concentrations were targeted for euglycaemia and maintained with a manual adjusted 20 % glucose solution over the clamp period of a maximum 6 hours. A glulisine-specific antibody was used to quantify glulisine concentrations by radioimmunoassay, while a non-specific insulin antibody and C-peptide based correction for endogenous insulin was used to estimate exogenous human insulin (RHI). At steady state (90 - 120 min), insulin glulisine and RHI had equivalent glucose utilization (GIR-AUCSS, 214 mg · kg-1 for glulisine, 209 mg · kg-1 for RHI) and infusion rates (GIRSS, 1050 and 995 mg · min-1 · kg-1). Both insulins also presented equal total glucose disposal (GIR-AUC0 - clamp end, 1050 and 995 mg · kg-1) and onset of activity within 20 min. Insulin glulisine and RHI showed parallel time concentration profiles with similar distribution and elimination, but the different antibodies employed for radioimmunoassay impeded a quantitative comparison. There were no noteworthy individual or within-group changes in cardiac repolarisation parameters measured by 12-lead ECG during insulin glulisine infusion. In conclusion, insulin glulisine and RHI show similar distribution and elimination profiles and equivalent glucodynamic efficacy on a molar, unit-per-unit basis.

1 This study was performed at FARMOVS-PAREXEL (Pty) Ltd., Bloemfontein, Republic of South Africa. This study was sponsored by Aventis Pharmaceuticals.

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1 This study was performed at FARMOVS-PAREXEL (Pty) Ltd., Bloemfontein, Republic of South Africa. This study was sponsored by Aventis Pharmaceuticals.

Dr. Reinhard H. A. Becker

Aventis Pharma Deutschland GmbH
Industriepark Höchst

65926 Frankfurt am Main

Germany

Phone: + 49(0)693054275

Fax: + 49 (0) 69 30 58 04 80

Email: Reinhard.Becker@aventis.com