[药品商品名称]： 波立维
[药品正式名称]： 硫酸氢氯吡格雷 Clopidogrel hydrogen sulfate
[药品英文名称]： Plavix
[基本药理]：  血小板聚集抑制剂，通过选择性抑制二磷酸腺苷（ADP）与血小板结合及继发由ADP介导的糖蛋白复合物活化。
[临床用途]：  适用于有过近期发作的中风、心肌梗塞和确诊外周动脉硬化的患者，波立维（氯吡格雷）可减少动脉粥样硬化性事件的发生（如心肌梗塞，中风和血管性死亡）。
[给药途径及用量]： 推荐剂量每日75mg，对老年患者和肾病患者不需调整剂量
[用法用量]： 推荐剂量为每天75mg，与或不与食物同服。对于老年患者和肾病患者不需调整剂量。
[不良反应]： 出血，波立维（氯吡格雷）严重出血事件的发生率分别为1.4% 胃肠道：如腹痛，消化不良，胃炎和便秘 皮疹和其它皮肤病 中枢和周围神经系统：头痛、眩晕、头昏和感觉异常 肝脏和胆道疾病 禁 忌 证对药品或本品任一成分过敏 严重的肝脏损伤 活动性病理性出血，如消化性溃疡或颅内出血 注意事项：氯吡格雷延长出血时间，对于有伤口（特别是在胃肠道和眼内）易出血的病人应慎用。病人应知服用波立维止血时间可能比往常长，同时病人应向医生报告异常出血情况，手术前和服用其它新药前病人应告知医生他们在服用波立维。 由于患有肾脏损伤病人使用氯吡格雷的经验极有限，因此这些病人应慎用波立维（氯吡格雷）。 严重肝病的病人可能有出血倾向，这类病人使用本药的经验极有限，应慎用波立维。 由于服用华法令也有出血倾向，所以服用时不推荐同时使用华法令。 对于同时服用易出现胃肠道伤口的药物（如非甾体消炎药）的病人应慎用波立维 未见服用本药后对驾驶或心理学检测产生影响 不建议孕妇及哺乳期妇女服用此药。在儿科使用的安全性和有效性还未明确。

PLAVIX (clopidogrel bisulfate) is an inhibitor of ADP-induced platelet aggregation acting by direct inhibition of adenosine diphosphate (ADP) binding to its receptor and of the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. Chemically it is methyl (+)-(S)-α-(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-acetate sulfate (1:1). The empirical formula of clopidogrel bisulfate is C16H16ClNO2S•H2SO4 and its molecular weight is 419.9.
Clopidogrel bisulfate is a white to off-white powder. It is practically insoluble in water at neutral pH but freely soluble at pH 1. It also dissolves freely in methanol, dissolves sparingly in methylene chloride, and is practically insoluble in ethyl ether. It has a specific optical rotation of about +56°.

PLAVIX for oral administration is provided as either pink, round, biconvex, debossed, film-coated tablets containing 97.875 mg of clopidogrel bisulfate which is the molar equivalent of 75 mg of clopidogrel base or pink, oblong, debossed film-coated tablets containing 391.5 mg of clopidogrel bisulfate which is the molar equivalent of 300 mg of clopidogrel base.

Each tablet contains hydrogenated castor oil, hydroxypropylcellulose, mannitol, microcrystalline cellulose and polyethylene glycol 6000 as inactive ingredients. The pink film coating contains ferric oxide, hypromellose 2910, lactose monohydrate, titanium dioxide and triacetin. The tablets are polished with Carnauba wax.

CLINICAL PHARMACOLOGY
Mechanism of Action and Pharmacodynamic Properties
Clopidogrel is a prodrug, one of whose metabolites is an inhibitor of platelet aggregation. A variety of drugs that inhibit platelet function have been shown to decrease morbid events in people with established cardiovascular atherosclerotic disease as evidenced by stroke or transient ischemic attacks, myocardial infarction, unstable angina or the need for vascular bypass or angioplasty. This indicates that platelets participate in the initiation and/or evolution of these events and that inhibiting platelet function can reduce the event rate.

Clopidogrel must be metabolized by CYP450 enzymes to produce the active metabolite that inhibits platelet aggregation. The active metabolite of clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet P2Y12 receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. This action is irreversible. Consequently, platelets exposed to clopidogrel's active metabolite are affected for the remainder of their lifespan (about 7 to 10 days). Platelet aggregation induced by agonists other than ADP is also inhibited by blocking the amplification of platelet activation by released ADP.

Because the active metabolite is formed by CYP450 enzymes, some of which are polymorphic or subject to inhibition by other drugs, not all patients will have adequate platelet inhibition.

Dose dependent inhibition of platelet aggregation can be seen 2 hours after single oral doses of PLAVIX. Repeated doses of 75 mg PLAVIX per day inhibit ADP-induced platelet aggregation on the first day, and inhibition reaches steady state between Day 3 and Day 7. At steady state, the average inhibition level observed with a dose of 75 mg PLAVIX per day was between 40% and 60%. Platelet aggregation and bleeding time gradually return to baseline values after treatment is discontinued, generally in about 5 days.

Pharmacokinetics
Absorption
After single and repeated oral doses of 75 mg per day, clopidogrel is rapidly absorbed. Mean peak plasma levels of unchanged clopidogrel (approximately 2.2-2.5 ng/mL after a single 75-mg oral dose) occurred approximately 45 minutes after dosing. Absorption is at least 50%, based on urinary excretion of clopidogrel metabolites.

Effect of Food
The effect of food on the bioavailability of the parent compound or active metabolite is currently not known.

Distribution
Clopidogrel and the main circulating inactive metabolite bind reversibly in vitro to human plasma proteins (98% and 94%, respectively). The binding is nonsaturable in vitro up to a concentration of 100 mcg/mL.

美国FDA批准Plavix的新医疗用途

美国FDA今天批准Plavix（商品名：波立维；通用名：氯吡格雷硫酸氢盐[Clopidogrel bisulfate]）用于患有一种称为急性 ST段抬高心肌梗死（ST-segment elevation myocardial infarction，STEMI）的心脏病发作的患者，这些患者将不进行冠状动脉修复（血管成形术）。
ST段抬高心肌梗死（STEMI）是由动脉突然完全堵塞造成的严重心脏病发作。在STEMI患者中，Plavix预防已受损的心脏血管的后续堵塞，后续堵塞将导致更多的心脏病发作和中风，且可能导致死亡。
FDA在1997年11月批准Plavix，用于降低患有急性冠脉综合征（acute coronary syndrome，ACS）的患者的血小板功能。血小板是粘性的血细胞，能帮助形成血栓，并能造成冠状动脉堵塞。
据美国心脏病协会称，每年估计有50万美国人有STEMI心脏病发作。
“Plavix已被证明能帮助患有某些类型心脏病发作的患者减少这些STEMI后续事件，”FDA的CDER主任Steven Galson医学博士称。
两项研究支持了Plavix治疗STEMI心脏病发作患者的有效性。一项大型研究，“氯吡格雷与美托洛尔在急性心肌梗塞中的试验”(Clopidogrel and Metoprolol in Myocardial Infarction Trial，COMMIT)研究，证明了Plavix与其它标准疗法（包括溶栓，一种溶解血栓的过程）联用时，减少了死亡率，也减少了心脏病发作复发、中风以及死亡的联合数量。COMMIT是一项进行于中国的针对46000名患者的随机双盲安慰剂对照试验。
COMMIT在中国的研究结果被“氯吡格雷作为辅助再灌注治疗”（CLARITY，Clopidogrel as Adjunctive Reperfusion Therapy）研究的结果所证实。CLARITY是一项对正在接受STEMI心脏病发作溶栓治疗的3500名患者的临床试验。CLARITY证明了氯吡格雷治疗组的冠状动脉血流优于安慰剂组。
Plavix的严重副作用包括流血和罕见的低白细胞计数或血栓性血小板减少性紫癜（低血小板计数，伴随自发性的出血和凝血）。Plavix由位于新泽西州的Bridgewater市的Sanofi Aventis公司生产。