Glimepiride

Glimepiride
Clinical data
Trade names	Amaryl
AHFS/Drugs.com	Monograph
MedlinePlus	a696016
License data	EU EMA: by INN;
Pregnancy; category	US: C (Risk not ruled out) ;
Routes of; administration	Oral (tablets)
ATC code	A10BB12 (WHO) ;
Legal status
Legal status	US: ℞-only ; In general: ℞ (Prescription only);
Pharmacokinetic data
Bioavailability	100%
Protein binding	>99.5%
Metabolism	Complete hepatic (1st stage through CYP2C9)
Elimination half-life	5–8 hours
Excretion	Urine (~60%), feces (~40%)
Identifiers
	IUPAC name 3-Ethyl-4-methyl-N-[2-(4-{[(trans-4-methylcyclohexyl)carbamoyl]sulfamoyl}phenyl)ethyl]-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxamide;
CAS Number	93479-97-1 ;
PubChem CID	3476;
IUPHAR/BPS	6820;
DrugBank	DB00222 ;
ChemSpider	16740595 ;
UNII	6KY687524K;
KEGG	D00593 ;
ChEBI	CHEBI:5383 ;
ChEMBL	CHEMBL1481 ;
ECHA InfoCard	100.170.771
Chemical and physical data
Formula	C24H34N4O5S
Molar mass	490.617 g/mol
3D model (JSmol)	Interactive image;
	SMILES O=C3C(/CC)=C(/C)CN3C(=O)NCCc1ccc(cc1)S(=O)(=O)NC(=O)N[C@H]2CC[C@H](C)CC2;
	InChI InChI=1S/C24H34N4O5S/c1-4-21-17(3)15-28(22(21)29)24(31)25-14-13-18-7-11-20(12-8-18)34(32,33)27-23(30)26-19-9-5-16(2)6-10-19/h7-8,11-12,16,19H,4-6,9-10,13-15H2,1-3H3,(H,25,31)(H2,26,27,30)/t16-,19- ; Key:WIGIZIANZCJQQY-RUCARUNLSA-N ;
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Glimepiride (original trade name Amaryl) is an orally available medium-to-long-acting sulfonylurea antidiabetic drug. It is sometimes classified as either the first third-generation sulfonylurea,^[1] or as second-generation.^[2]

Indications

Glimepiride is indicated to treat type 2 diabetes mellitus; its mode of action is to increase insulin secretion by the pancreas. However it requires adequate insulin synthesis as prerequisite to treat appropriately. It is not used for type 1 diabetes because in type 1 diabetes the pancreas is not able to produce insulin.^[3]

Contraindications

Its use is contraindicated in patients with hypersensitivity to glimepiride or other sulfonylureas.

Adverse effects

Side effects from taking glimepiride include gastrointestinal tract (GI) disturbances, occasional allergic reactions, and rarely blood production disorders including thrombocytopenia, leukopenia, and hemolytic anemia. In the initial weeks of treatment, the risk of hypoglycemia may be increased. Alcohol consumption and exposure to sunlight should be restricted because they can worsen side effects.^[3]

Pharmacokinetics

Two generic oral tablets of glimepiride, 2 mg each

Gastrointestinal absorption is complete, with no interference from meals. Significant absorption can occur within one hour, and distribution is throughout the body, 99.5% bound to plasma protein. Metabolism is by oxidative biotransformation, it is hepatic and complete. First, the medication is metabolized to M₁ metabolite by CYP2C9. M₁ possesses about ¹⁄₃ of pharmacological activity of glimepiride, yet it is unknown if this results in clinically meaningful effect on blood glucose. M₁ is further metabolized to M₂ metabolite by cytosolic enzymes. M₂ is pharmacologically inactive. Excretion in the urine is about 65%, and the remainder is excreted in the feces.

Mechanism of action

Like all sulfonylureas, glimepiride acts as an insulin secretagogue.^[4] It lowers blood sugar by stimulating the release of insulin by pancreatic beta cells and by inducing increased activity of intracellular insulin receptors.

Not all secondary sufonylureas have the same risks of hypoglycemia. Glibenclamide (glyburide) is associated with an incidence of hypoglycemia of up to 20–30%, compared to as low as 2% to 4% with glimepiride. Glibenclamide also interferes with the normal homeostatic suppression of insulin secretion in reaction to hypoglycemia, whereas glimepiride does not. Also, glibenclamide diminishes glucagon secretion in reaction to hypoglycemia, whereas glimepiride does not.^[5]

Interactions

Nonsteroidal anti-inflammatory drugs (such as salicylates), sulfonamides, chloramphenicol, coumadin and probenecid may potentiate the hypoglycemic action of glimepiride. Thiazides, other diuretics, phothiazides, thyroid products, oral contraceptives, and phenytoin tend to produce hyperglycemia.

References

↑ Hamaguchi T, Hirose T, Asakawa H, et al. (December 2004). "Efficacy of glimepiride in type 2 diabetic patients treated with glibenclamide". Diabetes Res. Clin. Pract. 66 Suppl 1: S129–32. doi:10.1016/j.diabres.2003.12.012. PMID 15563963.
↑ Davis SN (2004). "The role of glimepiride in the effective management of Type 2 diabetes". J. Diabetes Complicat. 18 (6): 367–76. doi:10.1016/j.jdiacomp.2004.07.001. PMID 15531188.
1 2 "Glimepiride: MedlinePlus Drug Information". nih.gov.
↑ Nissen SE, Nicholls SJ, Wolski K, et al. (April 2008). "Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial". JAMA. 299 (13): 1561–73. doi:10.1001/jama.299.13.1561. PMID 18378631.
↑ Davis, Stephen N. (2005). "60. Insulin, oral hypoglycemic agents, and the pharmacology of the endocrine pancreas". In Brunton, Laurence L.; Lazo, John S.; Parker, Keith L. (eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York: McGraw-Hill. p. 1636. ISBN 0-07-142280-3.

External links

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[pmid15563963-1] Hamaguchi T, Hirose T, Asakawa H, et al. (December 2004). "Efficacy of glimepiride in type 2 diabetic patients treated with glibenclamide". Diabetes Res. Clin. Pract. 66 Suppl 1: S129–32. doi:10.1016/j.diabres.2003.12.012. PMID 15563963.

[pmid15531188-2] Davis SN (2004). "The role of glimepiride in the effective management of Type 2 diabetes". J. Diabetes Complicat. 18 (6): 367–76. doi:10.1016/j.jdiacomp.2004.07.001. PMID 15531188.

[ncbi.nlm.nih.gov-3] 1 2 "Glimepiride: MedlinePlus Drug Information". nih.gov.

[pmid18378631-4] Nissen SE, Nicholls SJ, Wolski K, et al. (April 2008). "Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial". JAMA. 299 (13): 1561–73. doi:10.1001/jama.299.13.1561. PMID 18378631.

[G&G-5] Davis, Stephen N. (2005). "60. Insulin, oral hypoglycemic agents, and the pharmacology of the endocrine pancreas". In Brunton, Laurence L.; Lazo, John S.; Parker, Keith L. (eds.). Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York: McGraw-Hill. p. 1636. ISBN 0-07-142280-3.