Pharmacology: The primary mechanism of action of glimepiride in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic β-cells. In addition, extrapancreatic effects may also play a role in the activity of glimepiride. Glimepiride administration may lead to increased sensitivity of peripheral tissues to insulin. However, as with other sulphonylureas, the mechanism by which glimepiride lowers the blood glucose during long-term administration has not been clearly established.
A mild glucose lowering effect first appeared following oral doses as low as 0.5-0.6 mg in healthy subjects. The time required to reach maximum effect was about 2-3 hrs. The glucose lowering effect in all treatment groups was maintained for 24 hrs.
Pharmacokinetics: After oral administration, glimepiride is 100% absorbed from the GIT. There is significant absorption after 1 hr of administration and Cmax is achieved within 2-3 hrs. When glimepiride was given with meals, the Tmax was slightly increased and AUC was slightly decreased.
After IV dosing in normal subjects, the volume of distribution was 8.8 L. Total body clearance was 47.8 mL/min. Protein binding was >99.5%.
Glimepiride is completely metabolized by oxidative biotransformation after either an oral or IV dose. When radiolabelled glimepiride was given orally, about 60% of the total radioactivity was recovered in the urine in 7 days. About 40% of the radioactivity was recovered in the feces. No parent drug was recovered from the urine or feces.
Special Populations: Geriatrics: There was no much difference in glimepiride pharmacokinetics (AUC and weight adjusted clearance) between NIDDM patients >65 years and NIDDM patients <65 years.
Pediatrics: No pharmacokinetic study is done in pediatric patients.
Gender: There were no differences between males and females in the pharmacokinetics of glimepiride when adjustment in weight was done for differences in body weight.
Race: No pharmacokinetic studies to assess the effects of race have been performed.
Renal Insufficiency: Results of a clinical study showed that glimepiride serum levels decreased as renal function decreased.
A starting dose of glimepiride 1 mg may be given to NIDDM patients with kidney disease and the dose may be titrated based on fasting blood glucose levels.
Hepatic Insufficiency: No studies were performed in patients with hepatic insufficiency.