Glimepiride - How It Works
Clinical pharmacology details from the US FDA-approved label: how Glimepiride works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Glimepiride primarily lowers blood glucose by stimulating the release of insulin from pancreatic beta cells. Sulfonylureas bind to the sulfonylurea receptor in the pancreatic beta-cell plasma membrane, leading to closure of the ATP-sensitive potassium channel, thereby stimulating the release of insulin.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Glimepiride primarily lowers blood glucose by stimulating the release of insulin from pancreatic beta cells.
Sulfonylureas bind to the sulfonylurea receptor in the pancreatic beta-cell plasma membrane, leading to closure of the ATP-sensitive potassium channel, thereby stimulating the release of insulin.
12.2 Pharmacodynamics In healthy subjects, the time to reach maximal effect (minimum blood glucose concentrations) was approximately 2 to 3 hours after single oral doses of glimepiride tablets.
The effects of glimepiride on HbA 1c , fasting plasma glucose, and postprandial glucose have been assessed in clinical trials [see Clinical Studies ].
12.3 Pharmacokinetics Absorption Studies with single oral doses of glimepiride in healthy subjects and with multiple oral doses in patients with type 2 diabetes showed peak drug concentrations (C max ) 2 to 3 hours postdose.
When glimepiride was given with meals, the mean C max and AUC (area under the curve) were decreased by 8% and 9%, respectively.
Glimepiride does not accumulate in serum following multiple dosing.
The pharmacokinetics of glimepiride does not differ between healthy subjects and patients with type 2 diabetes.
Clearance of glimepiride after oral administration does not change over the 1 mg to 8 mg dose range, indicating linear pharmacokinetics.
In healthy subjects, the intraindividual and interindividual variabilities of glimepiride pharmacokinetic parameters were 15% to 23% and 24% to29%, respectively.
Distribution After intravenous dosing in healthy subjects, the volume of distribution (Vd) was 8.8 L (113 mL/kg), and the total body clearance (CL) was 47.8 mL/min.
Protein binding was greater than 99.5%.
Metabolism Glimepiride is completely metabolized by oxidative biotransformation after either an intravenous or oral dose.
The major metabolites are the cyclohexyl hydroxy methyl derivative (M1) and the carboxyl derivative (M2).
Cytochrome P450 2C9 is involved in the biotransformation of glimepiride to M1.
M1 is further metabolized to M2 by one or several cytosolic enzymes.
In animals, M1 possesses about one-third of the pharmacological activity of glimepiride, but it is unclear whether M1 results in clinically meaningful effects on blood glucose in humans.
Excretion When 14 C-glimepiride was given orally to 3 healthy male subjects, approximately 60% of the total radioactivity was recovered in the urine in 7 days.
M1 and M2 accounted for 80% to 90% of the radioactivity recovered in the urine.
The ratio of M1 to M2 in the urine was approximately 3:2 in two subjects and 4:1 in one subject.
Pharmacokinetics
12.3 Pharmacokinetics Absorption Studies with single oral doses of glimepiride in healthy subjects and with multiple oral doses in patients with type 2 diabetes showed peak drug concentrations (C max ) 2 to 3 hours postdose. When glimepiride was given with meals, the mean C max and AUC (area under the curve) were decreased by 8% and 9%, respectively. Glimepiride does not accumulate in serum following multiple dosing. The pharmacokinetics of glimepiride does not differ between healthy subjects and patients with type 2 diabetes. Clearance of glimepiride after oral administration does not change over the 1 mg to 8 mg dose range, indicating linear pharmacokinetics. In healthy subjects, the intraindividual and interindividual variabilities of glimepiride pharmacokinetic parameters were 15% to 23% and 24% to29%, respectively. Distribution After intravenous dosing in healthy subjects, the volume of distribution (Vd) was 8.8 L (113 mL/kg), and the total body clearance (CL) was 47.8 mL/min. Protein binding was greater than 99.5%. Metabolism Glimepiride is completely metabolized by oxidative biotransformation after either an intravenous or oral dose. The major metabolites are the cyclohexyl hydroxy methyl derivative (M1) and the carboxyl derivative (M2). Cytochrome P450 2C9 is involved in the biotransformation of glimepiride to M1. M1 is further metabolized to M2 by one or several cytosolic enzymes. M2 is inactive. In animals, M1 possesses about one-third of the pharmacological activit