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| Trade names | Prandin, Novonorm, Enyglid, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a600010 |
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| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | 56% (oral) |
| Protein binding | >98% |
| Metabolism | Liver oxidation andglucuronidation (CYP3A4-mediated) |
| Eliminationhalf-life | 1 hour |
| Excretion | Fecal (90%) andkidney (8%) |
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| ECHA InfoCard | 100.158.190 |
| Chemical and physical data | |
| Formula | C27H36N2O4 |
| Molar mass | 452.595 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 126 to 128 °C (259 to 262 °F) |
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Repaglinide is anantidiabetic drug in the class of medications known asmeglitinides, and was invented in 1983. Repaglinide is amedication used in addition to diet and exercise for blood sugar control in type 2 diabetes.[1] The mechanism of action of repaglinide involves promoting insulin release from β-islet cells of the pancreas; like other antidiabetic drugs, a main side effect concern is hypoglycemia.[1] It is sold byNovo Nordisk under the name ofPrandin in the United States, Gluconorm in Canada, Surepost in Japan, Repaglinide in Egypt, and Novonorm elsewhere. In Japan it is produced byDainippon Sumitomo Pharma.[2][failed verification]
Repaglinide is an oral medication used in addition to diet and exercise for blood sugar control in type 2 diabetes.[1]
Repaglinide is contraindicated in people with:
Common adverse events include:[1]
Metabolic
Respiratory
Gastrointestinal
Musculoskeletal
Other
Serious adverse events include:[1]
Pregnancy category C: safety in pregnant women has not been established.[1] Data is limited, and there is only one case report that notes no complications with the use of repaglinide during pregnancy.[3]
Caution should be taken in people with liver disease and decreased kidney function when using this medication.[1]
Repaglinide is a major substrate ofCYP3A4 and should not be administered concomitantly withgemfibrozil,clarithromycin orazoleantifungals such asitraconazole orketoconazole.[1] Administration of both repaglinide and one or more of these drugs results in an increase in plasma concentration of repaglinide and may lead tohypoglycemia. Co-administration of repaglinide and clopidogrel (a CYP2C8 inhibitor) may lead to a significant decrease in blood glucose levels due to a drug-drug interaction.[4] In fact, using these drugs together for even one day can cause repaglinide levels to increase over 5-fold...and may lead to significant hypoglycemia. Repaglinide should not be combined withsulfonylurea, because they have the same mechanism of action.[1]
Repaglinide lowers blood glucose by stimulating the release ofinsulin from the beta islet cells of thepancreas. It achieves this by closingATP-dependentpotassium channels in the membrane of thebeta cells. This depolarizes the beta cells, opening the cells'calcium channels, and the resulting calcium influx induces insulin secretion.[1]
Absorption: repaglinide has a 56%bioavailability when absorbed from the gastrointestinal tract. Bioavailability is reduced when taken with food; the maximum concentration decreases by 20%.
Distribution: The protein binding of repalglinide to albumin is greater than 98%.
Metabolism: repaglinide is primarily metabolized by the liver - specifically CYP450 2C8 and 3A4 - and to a lesser extent via glucuronidation. Metabolites of repaglinide are inactive and do not display glucose-lowering effects.
Excretion: repaglinide is 90% excreted in the feces and 8% in the urine. 0.1% is cleared unchanged in the urine. Less than 2% is unchanged in the feces.[1]
Precursor drugs to repaglinide were invented in late 1983 by scientists at Dr Karl Thomae GmbH, a German drug manufacturer located atBiberach an der Riß in southern Germany which was acquired byBoehringer Ingelheim in 1990. The drug that became repaglinide was later licensed by Boehringer to Novo Nordisk, which filed anInvestigational New Drug application for the compound with theFood and Drug Administration (FDA) in April 1992. Novo Nordisk filed itsNew 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 brandedPrandin because its quick onset and short duration of action concentrates its effect around meal time (theprandium was the Roman meal which is comparable to the modern lunch).[2]
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 theHatch-Waxman Act. This process, calledpatent 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 theU.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.[5]
Prior to the end of repaglinide's patent term, Novo Nordisk obtained a new patent, U.S. Patent 6,677,358 (January 2004), covering the combination therapy of repaglinide together with the generic anti-diabetic drugmetformin. This new patent was due to expire June 2018. In January 2011, a federal court ruled Novo Nordisk's new patent invalid on the grounds of obviousness, and unenforceable on the grounds of inequitable conduct on the part of Novo Nordisk's patent attorneys.[6]
