Pharmacokinetics and pharmacodynamics of the hydroxymetabolite of glimepiride (Amaryl) after intravenous administration

Drug Metabol Drug Interact. 1996;13(1):69-85. doi: 10.1515/dmdi.1996.13.1.69.


Glimepiride is a new sulphonylurea which is eliminated by the formation of a hydroxy-metabolite (hydroxy-gli) and a carboxymetabolite (carboxy-gli). Animal studies have shown hydroxy-gli to exhibit some hypoglycaemic effects while carboxy-gli does not appear to have any pharmacological activity. Pharmacokinetic and pharmacodynamic effects of hydroxy-gli were assessed in humans. 12 healthy male volunteers received an intravenous injection of hydroxy-gli (1.5 mg) or placebo in a single blind, randomised, cross-over study. Samples were collected for up to 24 hours (blood) or 48 hours (urine) following administration of hydroxy-gli or placebo. Hydroxy-gli significantly decreased the minimum serum concentration (Cmin) of glucose by 12% and the average serum glucose concentration over the first four hours of treatment (Cavg0-4) by 9% compared with placebo (P < or = 0.05). In addition, maximum serum C-peptide concentration (Cmax) and Cavg0-4 were both increased by 7% after hydroxy-gli (p < or = 0.05). Serum insulin concentrations (Cmax and Cavg0-4) increased by 4% but the differences from placebo were not statistically significant. No adverse events were reported during the study. In conclusion, the hydroxymetabolite of glimepiride shows pharmacological activity in human subjects.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Area Under Curve
  • Biotransformation
  • Blood Glucose / metabolism
  • C-Peptide / blood
  • Half-Life
  • Humans
  • Hydroxylation
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / urine
  • Injections, Intravenous
  • Insulin / blood
  • Male
  • Single-Blind Method
  • Sulfonylurea Compounds / administration & dosage
  • Sulfonylurea Compounds / pharmacokinetics*
  • Sulfonylurea Compounds / urine


  • Blood Glucose
  • C-Peptide
  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds
  • hydroxyglimepiride
  • glimepiride