Diabetes Care, Vol 17, Issue 9 1026-1030, Copyright © 1994 by American Diabetes Association

ARTICLES

Hypoglycemic activity of glyburide (glibenclamide) metabolites in humans

T Rydberg, A Jonsson, M Roder and A Melander
Hospital Pharmacy, Kristianstad County Central Hospital, Sweden.

OBJECTIVE--To assess the hypoglycemic effect and the insulin-releasing effect of the main glyburide (glibenclamide) metabolites 4-trans-hydroxy-glibenclamide (M1) and 3-cis-hydroxy-glibenclamide (M2) in humans. RESEARCH DESIGN AND METHODS--Eight healthy subjects participated in a placebo-controlled, randomized, single-blind crossover study with five single-dose tests, 3 months apart: 3.5 mg glibenclamide (Gb) orally, 3.5 mg Gb intravenously, 3.5 mg M1 intravenously, 3.5 mg M2 intravenously, and placebo intravenously, each in the fasting state. Standardized meals were given 0.5 and 5.5 h after each medication. Blood glucose levels were measured by a glucose oxidase method, and serum insulin concentrations were analyzed by a specific immunoassay. RESULTS--Blood glucose levels during the first 5 h were significantly lowered not only by Gb but also by M1 and M2. The mean +/- SE blood glucose reductions (versus placebo) expressed as percent of area under the curve (AUC) (0-5 h) were 18.2 +/- 3.3% for M1, 12.5 +/- 2.3% for M2, 19.9 +/- 2.1% for intravenous Gb, and 23.8 +/- 1.2% for Gb orally. Serum insulin levels were significantly increased by Gb as well as by M1 and M2. and M2. CONCLUSIONS--The two main metabolites of glyburide (glibenclamide) have a hypoglycemic effect in humans, which is due to increased insulin secretion.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Melander Kinetics-Effect Relations of Insulin-Releasing Drugs in Patients With Type 2 Diabetes: Brief Overview Diabetes, December 1, 2004; 53(suppl_3): S151 - S155. [Abstract] [Full Text] [PDF]

				D. Devineni, Y. H. Walter, H. T. Smith, J. S. Lee, P. Prasad, and J. F. McLeod Pharmacokinetics of Nateglinide in Renally Impaired Diabetic Patients J. Clin. Pharmacol., February 1, 2003; 43(2): 163 - 170. [Abstract] [Full Text]

				V. Vuksan, M. P Stavro, J. L Sievenpiper, V. Y. Koo, E. Wong, U. Beljan-Zdravkovic, T. Francis, A. L Jenkins, L. A Leiter, R. G Josse, et al. American Ginseng Improves Glycemia in Individuals with Normal Glucose Tolerance: Effect of Dose and Time Escalation J. Am. Coll. Nutr., June 1, 2000; 19(6): 738 - 744. [Abstract] [Full Text] [PDF]