美国食品和药物管理局近期审批通过了Byetta™(exenatide)。该药是激素类似物这一新型品中的第一个产品，主要用于二甲双胍和/或磺脲类降糖药不能良好控制血糖的2型糖尿病患者。预计2005年6月1日起可用于临床治疗。
Byetta能有效降低患者餐后和空腹血糖，对改善糖化血红蛋白水平也有一定的帮助。主要的作用机制可能是在血糖升高时促进胰岛素分泌，同时还有助于恢复进餐后第一相的胰岛素分泌，而后者的缺乏在2型糖尿病患者中非常常见。
目前Byetta有5mg和10mg两种剂型，以预混的形式在早餐和晚餐前经皮下注射给药。三项为期30周的对照研究表明，Byetta的副作用较少，剂量相关性的轻至重度恶心感是最常见的副反应，但随着治疗的继续，恶心感发生的频率和严重程度均会有所改善。联合Byetta和磺脲类药物治疗的患者发生低血糖的风险会有所增加，且存在剂量依赖性，因此减少磺脲类药物的剂量是一种可行的措施。大多数低血糖事件都可通过进食碳水化合物而纠正。目前的临床研究表明，Byetta联合二甲双胍治疗并不会增加低血糖事件的发生。此外，应用Byetta治疗的患者会出现诸如食欲减退、进食减少和/或体重减轻等情况，但专家认为无须因此而调整Byetta用量。
1型糖尿病患者及糖尿病酮症患者禁用Byetta治疗，Byetta也不可作为胰岛素的替代品用于治疗。不推荐存在终末期肾病或严重肾功能损害及严重胃肠道疾病的患者使用Byetta。同时服用可加快胃肠道吸收药物的患者须慎用Byetta。
【用法用量】
百泌达（Byetta，艾塞那肽注射液）仅用于皮下注射。应在大腿、腹部或上臂皮下注射给药。本品推荐起始剂量为5μg，每日两次，于早餐和晚餐（或每日2次正餐前，大约间隔6h或更长时间）前60分钟内给药。餐后不可给药。治疗1个月后，可根据临床反应将剂量增加至10μg。本品与二甲双胍或噻唑烷二酮类联用时，如果联用后不会因低血糖而需调整二甲双胍或噻唑烷二酮类的剂量，则可继续沿用原二甲双胍或噻唑烷二酮类的剂量。本品与磺脲类联用时，为降低低血糖的风险可考虑减少磺脲类的剂量。本品是澄清、无色的液体，如果出现颗粒或溶液混浊或有颜色则不能使用。
【药理毒理】
作用机制：肠降血糖素，如胰高血糖素样肽-1（GLP-1），从肠内释放入循环中后可以增强葡萄糖依赖性胰岛素分泌，并显示出其他抗高血糖药作用。艾塞那肽是拟肠降血糖素药，可以模拟葡萄糖依赖性胰岛素分泌增强作用和肠降血糖素其他抗高血糖药作用。
【药代动力学】
吸收：2型糖尿病患者皮下注射艾塞那肽，达到中位血浆浓度峰值的时间为2.1h。皮下注射剂量为10μg的艾塞那肽注射液，艾塞那肽平均峰浓度(Cmax)为211pg/mL，平均曲线下总面积(AUC0-inf)为1036pg?h/mL。在5－10μg的治疗剂量范围内艾塞那肽的暴露（AUC）按比例增加，但Cmax值增加比相应比例少。在腹部、大腿和手臂等部位皮下注射艾塞那肽注射液后暴露量相似。
 
分布：皮下注射单剂量艾塞那肽注射液，艾塞那肽的平均表观分布容积为28.3L。
代谢和消除：非临床研究显示艾塞那肽主要通过肾小球滤过及随后的蛋白水解而消除。在人类，艾塞那肽的平均表观清除率为9.1L/h，平均终末半衰期为2.4h。艾塞那肽的这些药物代谢动力学特征是非剂量依赖性的。对大多数人，给药后约10h艾塞那肽浓度仍可测。
【特殊人群】
肾功能受损：轻、中度肾功能损伤（肌酐清除率30－80mL/min）患者的艾塞那肽清除率仅轻度降低，因此无需调整艾塞那肽注射液的剂量。但是对于接受透析治疗的肾终末期疾病患者，艾塞那肽的平均清除率降低至0.9mL/min，而健康受试者为9.1mL/min。
 
肝功能受损：未在急、慢性肝功能受损患者中进行药代动力学研究。因为艾塞那肽主要经肾清除，故推测肝功能异常对艾塞那肽的血浆浓度可能没有影响（参见药代动力学，代谢和消除）。
老年人：患者（年龄范围22－73岁）群体药代动力学分析提示年龄对艾塞那肽的药代动力学特点没有影响。
儿童：未在儿童患者进行艾塞那肽研究。 
种族：对白种人、西班牙人和黑人患者进行的群体药代动力学分析提示种族对艾塞那肽的药代动力学没有明显影响。
肥胖：对肥胖（BMI≥30kg/m2）和非肥胖患者进行的群体药代动力学分析提示肥胖对艾塞那肽的药代动力学没有明显影响。
 
【不良反应】
百泌达（Byetta，艾塞那肽注射液）常见的不良事件为恶心、低血糖、腹泻、呕吐、头痛及不安感，其中以恶心最为常见。通常情况下，恶心为轻度到中度, 在患者开始治疗和增加剂量时发生频率高。但恶心是一过性的, 随着治疗时间的延长而减轻或消失。在与二甲双胍合用时，艾塞那肽不会增加低血糖的发生率，但是，在接受磺脲类药物治疗患者群中加入艾塞那肽，则可增加低血糖的发生率。

GENERIC NAME: exenatide
BRAND NAME: Byetta
DRUG CLASS AND MECHANISM: Exenatide is an injectable drug that reduces the level of sugar (glucose) in the blood. It is used for treating type 2 diabetes. Exenatide belongs in a class of drugs called incretin mimetics because these drugs mimic the effects of incretins. Incretins, such as human-glucagon-like peptide-1 (GLP-1), are hormones that are produced and released into the blood by the intestine in response to food. GLP-1 increases the secretion of insulin from the pancreas, slows absorption of glucose from the gut, and reduces the action of glucagon. (Glucagon is a hormone that increases glucose production by the liver.) All three of these actions reduce levels of glucose in the blood. In addition, GLP-1 reduces appetite. Exenatide is a synthetic (man-made) hormone that resembles and acts like GLP-1. In studies, exenatide-treated patients achieved lower blood glucose levels and experienced weight loss. Exenatide was approved by the FDA in May, 2005.
--------------------------------------------------------------------------------
Byetta
Generic name: Exenatide
--------------------------------------------------------------------------------
Why is Byetta prescribed?
Byetta is an injectable antidiabetic medication used to improve blood sugar control in people with type 2 diabetes whose current medications alone do not adequately control their blood sugar levels. Byetta is prescribed along with oral antidiabetic medications to enhance their effectiveness. It may be used with metformin alone or with metformin and sulfonylurea combined.
Type 2 diabetes occurs in people who are unable to produce or cannot properly utilize insulin. Insulin helps carry sugar from the bloodstream into the body's cells. In diabetes, the unused sugar causes abnormally high sugar levels in the bloodstream. Byetta is in a class of drugs known as incretin mimetics because it mimics the action of incretins—natural substances found in the body that help maintain normal blood sugar levels. Byetta stimulates cells that produce insulin in the pancreas, while also decreasing the amount of sugar the produced by the liver. In addition, it slows the passage of food from the stomach, thus slowing the rate that sugar is absorbed into the bloodstream. Byetta also decreases the appetite, which can help with weight control.
--------------------------------------------------------------------------------
Most important fact about Byetta
Your doctor has prescribed Byetta for your type 2 diabetes in addition to a plan that includes other antidiabetic medications and very specific dietary and exercise guidelines, and careful blood sugar monitoring. Failure to follow these guidelines or to take all of your medications as prescribed can result in serious and potentially life-threatening complications. Byetta cannot be used as a substitute for insulin in people with type 1 diabetes who need insulin to control their diabetes.
--------------------------------------------------------------------------------
How should you take Byetta?
Use the Byetta prefilled injection pen exactly as prescribed. A medical professional who is knowledgeable in the education and management of diabetes will instruct you in the use of this medication. You should inject your dose of Byetta in the thigh, abdomen, or upper arm within the one-hour period (60 minutes) before your morning and evening meals. Do not inject Byetta after a meal.
Your doctor may adjust your dose of Byetta or the other antidiabetic medications you take along with Byetta, depending on your response. Do not increase or decrease the dose on your own.
Pen needles for Byetta are not included with your prescription; you must purchase them separately.
If you miss a dose...
If you miss a dose of Byetta, skip the one you missed and return to your regular schedule. Do not take two doses at once or increase your next dose.
Storage instructions...
Store the Byetta pen in the refrigerator away from light and according to label instructions. Do not freeze Byetta or use product that has been frozen. Discard the pen after 30 days, even if there is still some medication left. Be sure to remove the needle from the Byetta pen before returning it to the refrigerator for storage. Medication can leak out through the needle and air bubbles can form in the cartridge.
--------------------------------------------------------------------------------
What side effects may occur?
Side effects cannot be anticipated. If any develop or change in intensity, tell your doctor as soon as possible. Only your doctor can determine if it is safe to continue using Byetta.
Side effects may include:
Diarrhea, dizziness, headache, feeling jittery, nausea, upset stomach, vomiting
--------------------------------------------------------------------------------
Why should Byetta not be prescribed?
Do not take Byetta if you have ever had an allergic reaction to it or any of its other ingredients.
--------------------------------------------------------------------------------
Special warnings about Byetta
Byetta used in combination with sulfonylurea antidiabetic drugs may result in dangerously low blood sugar. If you experience symptoms of headache, drowsiness, weakness, dizziness, confusion, irritability, confusion, hunger, fast heartbeat, sweating, or feeling jittery, follow your doctor's instructions for treating low blood sugar right away.
Byetta cannot be used as a substitute for insulin and is not recommended for use in type 1 diabetes or to treat diabetic ketoacidosis, a condition in which extremely high blood sugar levels and a lack of insulin, if left untreated, can lead to coma and death.
Byetta should not be used if you have severe kidney disease or severe digestive, intestinal, or stomach problems, especially when food empties from the stomach too slowly (gastroparesis).
--------------------------------------------------------------------------------
Possible food and drug interactions when taking Byetta
Byetta slows the rate that food passes from the stomach and may affect the absorption of other medications that you take by mouth. Your doctor may change the timing of your oral medicines and have you take them either on an empty stomach between meals or with a snack in between breakfast and dinner—not at the same mealtime as Byetta.
--------------------------------------------------------------------------------
Special information if you are pregnant or breastfeeding
The effects of Byetta in pregnancy have not been adequately studied. If you are pregnant or plan to become pregnant, you should not use Byetta unless your doctor determines that the benefits outweigh the risks.
It is not known whether Byetta appears in human breast milk or poses a risk to your breastfeeding child. If Byetta is essential to your health, your doctor may advise you to stop nursing until your treatment is finished.
--------------------------------------------------------------------------------
Recommended dosage for Byetta
ADULTS
--------------------------------------------------------------------------------
The usual starting dose of Byetta is 5 micrograms, injected twice daily in the one-hour period before eating breakfast and dinner. Each dose should be injected into the thigh, abdomen, or upper arm. Do not use Byetta after a meal. Depending on your response, your doctor may increase your dose to 10mcg. The maximum daily dose is 20 micrograms.
Byetta is supplied in 5-microgram and 10 microgram prefilled injection pens. Each pen contains 60 doses for a 30-day supply.
Byetta is a clear liquid and should be not be used if it contains particles or appears cloudy or discolored.
--------------------------------------------------------------------------------
Overdosage
According to the manufacturer, the exenatide (Byetta) autoinjector must be stored in a refrigerator between 36 °F (2 °C) and 46 °F (8 °C) before first use, and then at a temperature between 36 °F (2 °C) and 77 °F (25 °C). In hot weather, therefore, they should be refrigerated.[4] Exenatide (Byetta) 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.
------------------------------------------------------------
Mode of action
Exenatide is believed to facilitate glucose control in at least four ways:
Exenatide augments pancreas response (i.e. increases insulin secretion) in response to eating meals; the result is the release of a higher, more appropriate amount of insulin that helps lower the rise in blood sugar from eating. Once blood sugar levels decrease closer to normal values, the pancreas response to produce insulin is reduced; however, other drugs (like injectable insulin) are effective at lowering blood sugar, but can "overshoot" their target and cause blood sugar to become too low, resulting in the dangerous condition of hypoglycemia.
Exenatide also suppresses pancreatic release of glucagon in response to eating, which helps stop the liver from overproducing sugar when it is unneeded, which prevents hyperglycemia (high blood sugar levels).
Exenatide helps slow down gastric emptying and thus decreases the rate at which meal-derived glucose appears in the bloodstream.
Exenatide has a subtle yet prolonged effect to reduce appetite, promote satiety via hypothalamic receptors (different receptors than for amylin). Most people using Exenatide slowly lose weight, and generally the greatest weight loss is achieved by people who are the most overweight at the beginning of exenatide therapy. Clinical trials have demonstrated that the weight reducing effect continues at the same rate through 2.25 years of continued use. When separated into weight loss quartiles, the highest 25% experience substantial weight loss, and the lowest 25% experience no loss or small weight gain.
Exenatide reduces liver fat content. Fat accumulation in the liver or non-alcoholic fatty liver disease (NAFLD) is strongly related with several metabolic disorders, in particular low HDL cholesterol and high triglycerides, present in patients with type 2 diabetes. It became apparent that exenatide reduced liver fat in mice[5] and more recently in man.
In an open-label randomized controlled trial of 551 patients, exenatide treatment for 26 weeks was associated with 2.3 kg weight loss; however, gastrointestinal symptoms were more common in the exenatide group, including nausea (57.1%), vomiting (17.4%) and diarrhea (8.5%). For most patients, the nausea is mild to moderate and goes away entirely after a few days or weeks. Medical professionals who work with exenatide have stated that much of what is reported as nausea is actually a feeling of fullness. It is speculated that exenatide makes most patients need to eat less and until an adjustment is made to smaller portions, the result is the fullness feeling.
Advantages: While other treatment options share one or more of the first three characteristics, some diabetics specialists view exenatide as a significant improvement over other available diabetic medications, although most doctors do not use it as primary therapy at this time. Except for metformin and acarbose, all other available drugs for improving glucose control have been associated with weight gain.
Disadvantages: In addition to gastrointestinal adverse reactions, a relative disadvantage of exenatide is that it is administered by injection.
Reference: FDA Prescribing Information
------------------------------------------------------------
注：以下产品不同规格和不同价格，购买时请以电话咨询为准！
------------------------------------------------------------
原产地英文商品名:
Byetta 10mcg/dose 250mcg/ml 2.4ml/60dose/pen
原产地英文药品名:
Exenatide
中文参考商品译名:
Byetta 10微克/剂 250微克/毫升 /2.4毫升/60剂/支笔
中文参考药品译名:
艾塞那肽
生产厂家中文参考译名:
美国礼来公司与Amylin制药公司
生产厂家英文名:
cEli Lilly and Amylin company,USA

------------------------------------------------------------
原产地英文商品名:
Byetta 5mcg/dose 250mcg/ml 1.2ml/60dose/pen
原产地英文药品名:
Exenatide
中文参考商品译名:
Byetta 5微克/剂 250微克/毫升 1.2毫升/60剂/支笔
中文参考药品译名:
艾塞那肽
生产厂家中文参考译名:
美国礼来公司与Amylin制药公司
生产厂家英文名:
cEli Lilly and Amylin company,USA