Repaglinide

Repaglinide

File:Repaglinide.svg
Systematic (IUPAC) name
(S)-(+)-2-ethoxy-4-[2-(3-methyl-1-[2-(piperidin-1-yl)phenyl]butylamino)-2-oxoethyl]benzoic acid
Clinical data
[[Regulation of therapeutic goods |Template:Engvar data]]	EU EMA: Novonorm US FDA: Prandin
Pregnancy category	C (AU, US)
Routes of administration	Oral
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	56% (oral)
Protein binding	>98%
Metabolism	Hepatic oxidation and glucuronidation (CYP3A4-mediated)
Biological half-life	1 hour
Excretion	Fecal (90%) and renal (8%)
Identifiers
CAS Number	135062-02-1
ATC code	A10BX02 (WHO)
PubChem	CID 65981
DrugBank	APRD00439
Chemical data
Formula	C27H36N2O4
Molar mass	452.586 g/mol[[]]
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Repaglinide (Prandin in the U.S., GlucoNorm in Canada, NovoNorm elsewhere) is for the treatment of type II diabetes. It is supplied by Novo Nordisk.

Repaglinide belongs to the meglitinide class of blood glucose-lowering drugs.

Pharmacology

Repaglinide lowers blood glucose by stimulating the release of insulin from the pancreas. It achieves this by closing ATP-dependent potassium channels in the membrane of the beta cells. This depolarizes the beta cells, opening the cells' calcium channels, and the resulting calcium influx induces insulin secretion.

History

Precursor drugs to repaglinide were invented in late 1983 by scientists at Dr Karl Thomae GmbH, a German drug manufacturer located at Biberach an der Riß in southern Germany which was acquired by Boehringer Ingelheim in 1990. The drug that became repaglinide was later licensed by Boehringer to Novo Nordisk, which filed an Investigational New Drug application for the compound with the Food and Drug Administration (FDA) in April 1992. Novo Nordisk filed its New Drug Application (NDA) for Prandin in July 1997 and it was quickly approved, gaining FDA approval in December 1997. The drug was the first of the meglitinide class. It was branded Prandin because its quick onset and short duration of action concentrates its effect around meal time (the prandium was the Roman meal which is comparable to the modern lunch).

Intellectual property

After several attempts to file for U.S. patent protection, a filing was made in March 1990 which eventually became U.S. Patents 5,216,167 (June 1993), 5,312,924 (May 1994) and 6,143,769 (November 2000). After filing its NDA for repaglinide in 1997, Novo Nordisk applied for patent extension under the Hatch-Waxman Act. This process, called patent term restoration, allows drug patents to be extended based on the time that a drug spent in clinical trials and in the approval process. Previously it had been decided by the U.S. Patent and Trademark Office that the expiration date of U.S. Patents 5,216,167 and 5,312,924 would be 5 September 2006. In February 2001 Prandin's patent life was extended to 14 March 2009 in response to Novo Nordisk's patent term restoration application, with U.S. Patent 5,216,167 having been reissued as RE37035.

Generic status

Per the above paragraph, repaglinide will not become available as a generic drug in the United States before March 2009.

Supply

Repaglinide is available in 0.5 mg, 1 mg and 2 mg tablets.

Drug interactions

Repaglinide should not be administered concomitantly with gemfibrozil, clarithromycin or azole antifungals such as itraconazole or ketoconazole. Administration of both repaglinide and one or more of these drugs results in an increase in plasma concentration of repaglinide and may lead to hypoglycemia.

See also

• List of drugs

External links

• Prandin's label
• Prandin Repaglinide Tablets (manufacturer's website)
• RE37035, the reissued U.S. Patent 5,216,167
• U.S. Patent 5,312,924
• U.S. Patent 6,143,769
• U.S. Patent 6,677,358

fr:Répaglinide