Pharmacokinetics and pharmacodynamics of the hydroxymetabolite of glimepiride (Amaryl) after intravenous administration.
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.
Badian
M
M
Hoechst AG, Frankfurt/M, Germany.
Korn
A
A
Lehr
K H
KH
Malerczyk
V
V
Waldhäusl
W
W
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001711:Biotransformation; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D006207:Half-Life; D006801:Humans; D006900:Hydroxylation; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood; D008297:Male; D016037:Single-Blind Method; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; C104273:hydroxyglimepiride; C057619:glimepiride