Glimep Mechanism of Action

Pharmacology: Pharmacokinetics: The absolute bioavailability of glimepiride is complete. Food intake has no relevant influence on the absorption. Maximum serum concentration (Cmax) are reached approximately 2.5 hrs after oral intake (309mg/mL during multiple dosing of 4 mg daily) and there's a linear relationship between dose and both Cmax and AUC (area under the time-concentration curve). Glimepiride has a very low distribution volume (approximately 8.8 L) which is roughly equal to the albumin distribution space, high protein binding (>99%) and a low clearance (approximately 48mL/min). Mean dominant serum half-life which is of relevance for the serum concentrations under multiple-dose conditions is about 5-8 hrs. After high doses, slightly longer half-lives were noted.
After a single dose of radiolabelled glimepiride, 58% of the radioactivity was recovered in the urine and 35% in the feces. No unchanged substance was detected in the urine. Two metabolites, most probably resulting from hepatic metabolism, were identified both in urine and feces. The hydroxy derivative and carboxy derivatives. After oral administration of glimepiride, the terminal half-lives of these metabolites were 3-6 and 5-6 hrs, respectively. Comparison of single and multiple once-daily dosing revealed no significant differences in pharmacokinetics and the intra individual variability was very low. There was no relevant cumulation. Pharmacokinetics were similar in males and females, as well as in young and elderly (>65 years) patients.
In patients with low creatinine clearance, there was a tendency for glimepiride clearance to increase and for average serum concentrations to decrease, most probably resulting from a more rapid elimination because of lower protein binding. Renal elimination of 2 metabolites was impaired. Overall, no additional risk of cumulation is to be assumed in such patients. Pharmacokinetics in 5 non-diabetic patients after bile duct surgery were similar to those in healthy persons. In animals, glimepiride is excreted into milk.