HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cernea, S. Articles by Raz, I. Search for Related Content PubMed PubMed Citation Articles by Cernea, S. Articles by Raz, I. Social Bookmarking                What's this?

Dose-Response Relationship of Oral Insulin Spray in Healthy Subjects

¹ Hadassah Hebrew University Hospital, Diabetes Unit, Internal Medicine Department, Jerusalem, Israel
² Generex Biotechnology, Toronto, Canada

Address correspondence and reprint requests to Itamar Raz, Diabetes Unit, Dept of Medicine, Hadassah Hospital, POB 12000, Jerusalem, Israel 91120. E-mail: ntv502{at}netvision.net.il

OBJECTIVE—To evaluate the pharmacodynamic and pharmacokinetic properties and the dose-ranging effects of an oral insulin spray in comparison with subcutaneous regular insulin.

RESEARCH DESIGN AND METHODS—In this randomized, five-way, cross-over study, seven healthy volunteers were assessed under euglycemic clamp and received four different doses of oral spray and one dose of subcutaneous regular insulin.

RESULTS—The time to maximum insulin concentration was shorter for oral insulin than for subcutaneous insulin (25.9 ± 9 vs. 145.7 ± 49.5 min, P < 0.05). Maximum serum insulin levels (C_max) were comparable between the subcutaneous and 20 puffs of oral insulin (39.1 ± 19.6 vs. 34.0 ± 7.4 µU/ml, NS). The Ins-AUC_0–120 (area under the curve from 0 to 120 min for serum insulin) (339.8 ± 218, 681.3 ± 407, and 1,586.7 ± 8 µU/ml, P < 0.05) and C_max (7.6 ± 2.8, 16.4 ± 9.3, and 39.1 ± 19.6 µU/ml, P < 0.005) proved a dose-response relationship for the three doses of oral insulin (5, 10, and 20 puffs, respectively). Oral insulin had an earlier onset of action (31.7 ± 12 vs. 77.8 ± 3 min, P < 0.05), earlier peak (44.2 ± 10 vs. 159.2 ± 68 min, P < 0.05), and a shorter duration of action (85.1 ± 25 vs. 319.2 ± 45 min, P < 0.05) compared with subcutaneous insulin. The maximum metabolic effect (1.7 ± 1.0, 3.09 ± 1.7, and 4.6 ± 1.5 mg · kg^–1 · min^–1, P < 0.05) and the GIR-AUC_0–120 (amount of glucose infused from 0 to 120 min) (106.7 ± 74.3, 162.9 ± 116.1, and 254 ± 123 mg/kg) increased in a dose-dependent relationship for the three doses.

CONCLUSIONS—Oral insulin was absorbed in direct relation to the amount given and had a faster onset and a shorter duration of action compared with subcutaneous regular insulin. A dose-response relationship in the absorption and metabolic effect of the oral insulin was noted.

Abbreviations: AUC, area under curve • GIR, glucose infusion rate • Ins-AUC, AUC for serum insulin

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. J. Neumiller, P. S. Odegard, J. R. White Jr., S. M. Setter, and R. K. Campbell Looking to the Future: Focus on DPP-4 Inhibitors for the Treatment of Type 2 Diabetes and Emerging Therapies The Diabetes Educator, March 1, 2008; 34(2): 183 - 200. [Abstract] [Full Text] [PDF]