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Related Experiment Videos

Is there a concentration-effect relationship for sulphonylureas?

A Melander1, R Donnelly, T Rydberg

  • 1NEPI Foundation, Malmö, Sweden. regina.ringkvist@nepi.a.se

Clinical Pharmacokinetics
|April 16, 1998
PubMed
Summary

Sulfonylureas effectively manage type 2 diabetes by stimulating insulin release. Newer research reveals longer glibenclamide half-lives and active metabolites, suggesting current maximum doses may be too high.

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Area of Science:

  • Pharmacology
  • Endocrinology
  • Metabolism

Background:

  • Sulfonylureas are primary oral agents for type 2 diabetes (non-insulin-dependent diabetes mellitus, NIDDM).
  • These drugs enhance insulin secretion from pancreatic beta cells.
  • Pharmacokinetic variations influence clinical outcomes like efficacy, duration, and hypoglycemia risk.

Purpose of the Study:

  • To investigate the pharmacokinetics and pharmacodynamics of sulfonylureas, specifically glibenclamide.
  • To evaluate the concentration-effect relationships of glibenclamide and its metabolites.
  • To assess potential tolerance development under continuous drug exposure.

Main Methods:

  • Utilized improved analytical sensitivity for pharmacokinetic studies.
  • Employed integrated pharmacokinetic-pharmacodynamic modeling in healthy volunteers.

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  • Analyzed both single and multiple dose conditions, including oral and intravenous administration.

    • Main Results:

    • Glibenclamide's elimination half-life is longer than previously recognized.
    • Two glibenclamide metabolites exhibit significant hypoglycemic activity.
    • Continuous sulfonylurea exposure may lead to tolerance via beta cell desensitization.

    Conclusions:

    • Concentration-effect relationships for glibenclamide and its metabolites are established.
    • Tolerance may develop with sustained therapeutic concentrations.
    • Current maximum daily doses for many sulfonylureas might be excessive.