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Exenatide (, INN, marketed as Byetta, Bydureon) is a glucagon-like peptide-1 agonist (GLP-1 agonist) medication, belonging to the group of incretin mimetics, approved in April 2005 for the treatment of diabetes mellitus type 2. Exenatide in its Byetta form is administered as a subcutaneous injection (under the skin) of the abdomen, thigh, or arm, any time within the 60 minutes before the first and last meal of the day. A once-weekly injection has been approved as of January 27, 2012 under the trademark Bydureon. It is manufactured by Amylin Pharmaceuticals and commercialized by Astrazeneca. == Chemistry and pharmacology == Exenatide is a synthetic version of exendin-4, a hormone found in the saliva of the Gila monster that was first isolated by John Eng MD in 1992 while working at the Veterans Administration Medical Center in the Bronx, New York. It displays biological properties similar to human glucagon-like peptide-1 (GLP-1), a regulator of glucose metabolism and insulin secretion. According to the package insert, exenatide enhances glucose-dependent insulin secretion by the pancreatic beta-cell, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying, although the mechanism of action is still under study. Exenatide is a 39-amino-acid peptide, an insulin secretagogue, with glucoregulatory effects. Exenatide was approved by the FDA on April 28, 2005 for patients whose diabetes was not well-controlled on other oral medication.〔(CDER Drug and Biologic Approvals for Calendar Year 2005 ), from the U.S. Food and Drug Administration. Accessed August 28, 2008.〕 The medication is injected subcutaneously twice per day using a filled pen-like device. The abdomen is a common injection site, after the area is cleaned with an alcohol pad. A new pen must first be tested to see if the medicine is flowing. The incretin hormones GLP-1 and glucose-dependent insulinotropic peptide (GIP) are produced by the L and K endocrine cells of the intestine following ingestion of food. GLP-1 and GIP stimulate insulin secretion from the beta cells of the islets of Langerhans in the pancreas. Only GLP-1 causes insulin secretion in the diabetic state; however, GLP-1 itself is ineffective as a clinical treatment for diabetes as it has a very short half-life ''in vivo''. Exenatide bears a 50% amino acid homology to GLP-1 and it has a longer half-life ''in vivo''. Thus, it was tested for its ability to stimulate insulin secretion and lower blood glucose in mammals, and was found to be effective in the diabetic state. In studies on rodents, it has also been shown to increase the number of beta cells in the pancreas. Commercially, exenatide is produced by direct chemical synthesis. Historically, exenatide was discovered as Exendin-4, a protein naturally secreted in the saliva and concentrated in the tail of the Gila monster. Exendin-4 shares extensive homology and function with mammalian GLP-1, but has a therapeutic advantage in its resistance to degradation by DPP-IV (which breaks down GLP-1 in mammals) therefore allowing for a longer pharmacological half life. The biochemical characteristics of Exendin-4 enabled consideration and development of exenatide as a diabetes mellitus treatment strategy. Given this history, exenatide is sometimes referred to as "lizard spit". Subsequent clinical testing led to the discovery of the also desirable glucagon and appetite-suppressant effects. In its twice daily Byetta form, exenatide raises insulin levels quickly (within about ten minutes of administration) with the insulin levels subsiding substantially over the next hour or two. A dose taken after meals has a much smaller effect on blood sugar than one taken beforehand. The effects on blood sugar diminish after six to eight hours.〔 In its Byetta form, the medicine is available in two doses: 5 mcg. and 10 mcg. Treatment often begins with the 5 mcg. dosage, which is increased if adverse effects are not significant.〔 Its once weekly Bydureon form is unaffected by the time between the injection and when meals are taken. Bydureon has the advantage of providing 24‑hour coverage for blood sugar lowering, while Byetta has the advantage of providing better control of the blood sugar spike that occurs right after eating. Per the FDA label for Bydureon, Bydureon lowers HbA1c blood sugar by an average of 1.6%, while Byetta lowers it by an average of 0.9%. Both Byetta and Bydureon have similar weight loss benefits. Per the FDA approved Bydureon label, the levels of nausea are lower for Bydureon patients than for Byetta patients. According to the manufacturer, the autoinjector must be stored in a refrigerator between 2 °C (36 °F) and 8 °C (46 °F) before first use, and then at a temperature between 2 °C (36 °F) and 25 °C (77 °F). In hot weather, therefore, they should be refrigerated.〔(Diabetes Monitor Accessed September 6, 2008 ).〕 Pens contain sixty doses designed to be used twice a day for 30 days. Exenatide received US Patent (5,424,286 ) which was filed May 24, 1993. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Exenatide」の詳細全文を読む スポンサード リンク
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