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英文药名: Lyrica (Pregabalin Capsules)
中文药名: 普瑞巴林胶囊
药品名称
产品名称: 普瑞巴林
别名: C1-1008
化学名称: (3S)-3-氨甲基-5-甲基己酸
分子式: C8H17NO2
分子量: 159.23
性状：白色结晶性粉末
药品简介
辉瑞公司开发的pregabalin(普瑞巴林) [CI 1008]是一种γ氨基丁酸结构类似物，是一种具有抗痉挛作用的化合物。该化合物正在美国进行治疗癫痫的III期临床试验。该化合物的其他适应症包括神经病理性疼痛、泛发性焦虑症和社交恐怖症。辉瑞公司暂时停止了在美国进行的普瑞巴林治疗神经病理性疼痛的III期临床试验，因为动物实验发现该化合物有可能引起小鼠肿瘤，实际上之前的研究没有发现普瑞巴林有任何潜在的致瘤性。辉瑞公司称正与FDA协商以解决这一问题，但向FDA提交新药申请的计划不受影响。治疗癫痫和焦虑症的临床试验仍继续进行。普瑞巴林的抗痉挛作用机理还不完全明了，实验发现普瑞巴林可以和细胞的加巴喷丁结合位点结合，但是否是和加巴喷丁类似的作用机理和不得而知。临床前研究发现普瑞巴林的抗痉挛特性和加巴喷丁类似，但活性更强。一项II期临床试验发现普瑞巴林对顽固性局灶性癫痫仍有抗痉挛作用。
药理药效
普瑞巴林是一种新型γ-氨基丁酸(GABA)受体激动剂,能阻断电压依赖性钙通道,减少神经递质的释放,临床主要用于治疗外周神经痛以及辅助性治疗局限性部分癫痫发作。
药代动力学：在随机、安慰剂对照交叉临床试验中，29名健康志愿者接受普瑞巴林 1-300mg单次口服。普瑞巴林吸收迅速，tmax在1.3小时内达到。Cmax和AUC 0-∞和给药剂量成正比，两者的范围分别为0.0383-9.46μg/ml和0.223-66.3μg x h-1xml-1。清除半衰期的范围为4.6-6.8h，和剂量无关。89.8%的给药剂量以原型形式从尿中排出。
适应症
-广泛性焦虑障碍 (Generalized Anxiety Disorder GAD)
-糖尿病性外周神经病 (Diabetic Peripheral Neuropathy DPN)
-疱疹后神经痛 (Post-herpetic Neuralgia PHN)
-纤维肌痛综合征 (Fibromyaigia Syndrome FMS)
-癫痫的辅助治疗
不良反应
一项双盲、安慰剂对照试验发现，165名局部发作型癫痫病人在原有治疗基础上加上普瑞巴林治疗（剂量为50、100、150、300和600 mg/day，每日两次）。最大剂量时大部分患者的耐受性良好。头晕和嗜睡是最常出现的不良反应，600mg/day剂量组的发生率最高，头晕发生率为42%，嗜睡的发生率为29%。而安慰剂组这两种不良反应的发生率均为11%。大部分不良反应为轻到中度。8名患者因不良反应退出了试验，这些患者均是300mg/day 和600mg/day剂量组的患者。泛发型焦虑症和社交恐怖症患者所进行的临床试验也发现头晕和嗜睡是最常出现的不良反应。
临床试验
在2003年6月美国神经病学会议上，辉瑞公司公布的pregabalin(普瑞巴林)试验数据表明，该药可以快速有效的治疗广泛性焦虑障碍(GAD)的各种症状。数据综合自5个安慰剂对照试验，包括II期临床试验和III期临床先导试验。数据表明普瑞巴林对GAD急性治疗的效果广泛、快速。普瑞巴林在使用第一周就缓解了每个参加试验患者的精神和身体焦虑症状。在其中一个先导试验中，抗抑郁药文拉法新（venlafaxine）作为对照药物。与之相比普瑞巴林改善精神和躯体焦虑症状显著快，文拉法新没能在第一周就改善患者焦虑症状。在另一个先导试验中，以苯并二氮卓类药物阿普唑仑(alprazolam)为对照药品，数据再次显示普瑞巴林显著快速的改善精神和躯体焦虑症状，在第一周就有所改善，而阿普唑仑在第一周只改善了精神症状。2002年的一项双盲试验考察疱疹感染后神经痛患者服用300 mg、600mg 普瑞巴林8周后与安慰剂的差别，评价方式为平均疼痛得分和SF-McGill疼痛调查表（SF-MPQ）。治疗后第一周疗效就很明显，并且效果持续到研究结束。而另一个研究表明该药效果与剂量相关。在健康志愿者和肾功能不好的慢性疼痛患者中的药代动力学考察表明药物释放呈线性，两者的药物消除率与肌酐清除率有关，在同时服用口服胰岛素、利尿剂和抗糖尿病药物时不必调整该药剂量。
药物相互作用
不被细胞色素P450系统代谢，因此，很少与其他药物发生相互作用。体外研究显示 其浓度为1 000umol.L-1 时对 CYP1A2，2A6，2C9，2C19，2D6和2El或 3A4无抑制作用；也不影响抗癫痫药(如丙戊酸钠、苯妥英钠、拉莫三嗪、酰胺 咪嗪、苯巴比妥、托吡酯)、口服避孕药、口服降糖药、利尿剂、胰岛素等的药动学。本品与氧可酮同用时，其识别功能降低，运动功能损伤增强。与劳拉西泮和乙醇也有相加作用 。
近日美国FDA批准了Lyrica (pregabalin，普瑞巴林)用于治疗纤维肌痛，这种病症表现为疼痛、疲乏与睡眠障碍，这是FDA批准的第一个用于治疗纤维肌痛的药物。Lyrica可减少纤维肌痛患者的疼痛与提高患者的日常活动功能。
公司官员说道：“这项批准将给很多患者提供一种减少疼痛的药物，消费者应了解该药对一部分患者没有效果”。纤维肌痛患者在美国有300-600万，患者多为青中年女性。
Lyrica由辉瑞公司生产，之前已被批准用于部分性癫痫发作、带状疱疹疼痛与糖尿病神经损害。
普瑞巴林可有效治疗纤维肌痛症
一项随机、双盲、多中心、安慰剂、对照研究，用于评估普瑞巴林(CI-1008)用于治疗纤维肌痛症的安全性和有效性。研究结果表明，与安慰剂相比，普瑞巴林组平均疼痛评分显著降低，这为该项研究的主要疗效分析。将来会对这些初步的结果进行进一步的分析。
纤维肌痛的主要特点是广泛的慢性肌肉骨骼疼痛和压痛。纤维肌痛的病理生理比较复杂，并且目前对它的了解还不透彻，但纤维肌痛是一种致残性疾病，严重影响了患者的生活质量。
该研究对普瑞巴林灵活剂量300 mg/d-450 mg/d，每天两次与安慰剂治疗纤维肌痛患者进行了比较。该项研究在日本的45个研究中心共纳入了501例患者（普瑞巴林组251例，安慰剂250例）。
这项研究的初步结果表明，研究中出现的最常见的副作用包括嗜睡、头晕、体重增加、便秘、感觉异常、外周水肿和视力模糊。
Pain from Damaged Nerves (neuropathic pain)
Diabetes and shingles can damage your nerves. Pain from damagednervesmayfeel sharp, burning, tingling, shooting, or numb. If you have diabetes, the paincan be in your arms, hands, fingers, legs, feet, or toes. If you have shingles, thepain is in the area of your rash. You may experience this kind of pain even with avery light touch. LYRICA can help relieve the pain. Some people taking LYRICAhad less pain by the end of the first week of LYRICA therapy. LYRICA may notwork for everyone.
Partial Seizures
Partial seizures start in one part of the brain.Aseizurecanmakeyoufearful,confused, or just feel "funny". You may smell strange smells. A seizure maycause your arm or leg to jerk or shake. It can spread to other parts of yourbrain, make you pass out, and cause your whole body to start jerking.
LYRICA can lower the number of seizures for people who are already takingseizure medicine.
Fibromyalgia
Fibromyalgia is a condition which includes widespread muscle pain and difficulty
performing daily activities. LYRICA can help relieve the pain and improvefunction. Some people taking LYRICA had less pain by the end of the first weekof LYRICA therapy. LYRICA may not work for everyone.
Who Should Not Take LYRICA?
Do not take LYRICA if you are allergic to any of its ingredients. Theactive ingredient is pregabalin. See the end of this leaflet for a complete list ofingredients in LYRICA.
What should I tell my doctor before taking LYRICA?
Tell your doctor about all your medical conditions, including if you:
• have any kidney problems or get kidney dialysis
• have heart problems including heart failure
• have a bleeding problem or a low blood platelet count
• are pregnant or plan to become pregnant. It is not known if LYRICAmay harm your unborn baby. You and your doctor will have to decide ifLYRICA is right for you while you are pregnant.
• are breastfeeding. It is not known if LYRICA passes into breast milk andif it can harm your baby. You and your doctor should decide whether youshouldtakeLYRICA or breastfeed, but not both.
Tell your doctor about all the medicines you take including prescriptionor non- prescription medicines, vitamins or herbal supplements. LYRICAand othermedicines may affect each other. Especially tell your doctor if youtake:
• angiotensin converting enzyme (ACE) inhibitors. You may have a higherchance for swelling and hives if these medicines are taken with LYRICA.See "What is the most important information I should know aboutLYRICA?"
• Avandia®(rosiglitazone) or Actos®(pioglitazone) for diabetes. You mayhave a higher chance of weight gain or swelling if these medicines aretaken with LYRICA. See "What are the possible side effects of LYRICA."
• any narcotic pain medicine (such as oxycodone), tranquilizers ormedicines for anxiety (such as lorazepam). You may have a higher chancefor dizziness and sleepiness if these medicines are taken with LYRICA. See"Whatisthemostimportant information I should know about LYRICA?"
• any medicines that make you sleepy
Know all the medicines you take. Keep a list of them with you to show yourdoctor and pharmacist each time you get a new medicine.
Tell your doctor if you plan to father a child. Animal studies showed thatpregabalin, the active ingredient in LYRICA, made male animals less fertile andcaused sperm abnormalities. Also, in animal studies, birth defects occurred in theoffspring of male animals who were treated with pregabalin. It is not known ifthese effects would happen in people.
How should I take LYRICA?
• Take LYRICA exactlyasprescribed.Yourdoctormayadjustyourdoseduringtreatment. Do not change your dose without talking to your doctor.
• Do not stop taking LYRICA suddenly without talking to your doctor. If youstop taking LYRICA suddenly, you may have headaches, nausea, diarrheaor trouble sleeping. Talk with your doctor about how to slowly stopLYRICA.
• LYRICA is usually taken 2 or 3 times a day, depending on your medicalcondition. Your doctor will tell you how much LYRICA to take and when totake it. Take LYRICA at the same times each day.
• LYRICA may be taken with or without food.
• If you miss a dose by a few hours, take it as soon as you remember. If it
is close to your next dose, just take LYRICA at your next regular time. Donot take two doses at the same time.
• If you take too much LYRICA, call your doctor or poison control center orgo to the nearest emergency room right away.
What Should I Avoid While Taking LYRICA?
• Do not drive a car, work with machines, or do other dangerousactivities until you know how LYRICA affects how alert you are.See "What is the most important information I should know aboutLYRICA?"
• Do not drink alcohol while taking LYRICA. LYRICA and alcohol canaffect eachother and increase side effects such as sleepiness anddizziness. This can be dangerous.
Do not take other medicines without talking to your doctor. Othermedicines include prescription and non-prescription medicines, vitamins, andherbal supplements. LYRICA and other medicines may affect each other andincrease the side effects of swelling, sleepiness and dizziness. Be especiallycareful about medicines that make you sleepy (such as sleeping pills, anxietymedicines, tranquilizers and some antihistamines, pain relievers and seizuremedicines).
What are the possible side effects of LYRICA?
LYRICA may cause side effects including:
• allergic reactions. See "What is the most important information I shouldknow about LYRICA?"
• weight gain and swelling of the hands and feet (edema). Weightgain may affect the management of diabetes. Weight gain and swellingcan also be a serious problem for people with heart problems.
• dizziness and sleepiness. See "What is the most important informationI should know about LYRICA?"
• eyesight problems. See "What is the most important information Ishould know about LYRICA?"
• unexplained muscle problems, such as muscle pain, soreness, orweakness. If you develop these symptoms, especially if you also feel sickand have a fever, tell your doctor right away.
The most common side effects of LYRICA are:
• dizziness
• blurry vision
• weight gain
• sleepiness
• trouble concentrating
• swelling of hands and feet
• dry mouth
LYRICA caused skin sores in animals. Although skin sores were not seen instudies in people, if you have diabetes, you should pay extra attention to yourskin while taking LYRICA and tell your doctor of any sores or skin problems.
LYRICA may cause some people to feel "high." Tell your doctor, if you haveabused prescription medicines, street drugs, or alcohol in the past.
Tell your doctor about any side effect that bothers you or that does not go away.
These are not all the side effects of LYRICA. For more information, ask yourdoctor or pharmacist.
How should I store LYRICA?
• Store LYRICA at room temperature, 59 to 86° F (15 to 30° C) in its original
package.
• Safely throw away LYRICA that is out of date or no longer needed.
• Keep LYRICA and all medicines out of the reach of children.
欧盟批准辉瑞的Lyrica用于神经痛的缓解
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