ST JOHN'S WORT AND PLATELET ANTI-AGGREGATORY EFFECT OF CLOPIDOGREL

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项研究旨在确定一种名为圣约翰麦芽汁的草药疗法是否有效地增强了一种名为氯吡格雷(以Plavix的名称销售)的药物的活性。Plavix抑制血小板功能，就像阿司匹林一样。血小板是血流中的微小细胞，聚集在一起止血。这种聚集被称为聚集，这是正常的血小板所做的事情。当一个人服用Plavix时，它会停止血小板的作用，因此被称为抗血小板药物。圣约翰草(不受FDA监管)是治疗抑郁症的一种替代疗法。许多服用的药物，包括圣约翰草和Plavix，都会通过肝脏，需要一种名为CYP3A4的酶来代谢，这样身体才能将它们用于预期的目的。现在已经知道，圣约翰麦芽汁可以刺激肝脏酶CYP3A4的产生。因此，在服用Plavix与圣约翰草联合使用的患者中，我们预计会看到Plavix对血小板的增加作用。在最近的一项研究中，我们发现并不是所有的患者对Plavix的反应都是相同的。换句话说，在一些患者中，它比其他患者更有效。对Plavix的反应是通过血液测试来确定的，该测试测量了血小板功能的百分比，即口服Plavix后保持功能的血小板总数的百分比。对Plavix有反应的患者在Plavix后将有70%的血小板活性抑制，而对Plavix有反应的低反应者将有70%的血小板抑制反应。除了测量血小板功能外，我们还想知道，当服用圣约翰麦芽汁时，这种肝酶CYP3A4的活性是否真的有可测量的增加。用红霉素呼气试验(ERMBT)测定细胞色素P3A4的活性。这项研究招募了100名健康的成年男性和女性志愿者，年龄在18-60岁之间，不分种族和民族。被确定为Plavix应答者的受试者将被排除在研究之外。被确定为对Plavix低-低反应者的受试者将被包括在研究中。这项研究的主要目的是观察圣约翰草与Plavix联合使用是否会增加Plavix的抗血小板作用。我们还想确定圣约翰麦芽汁是否在可测量的量上增强肝酶CYP3A4，并将使用ERMBT进行测量。第二个目的是，根据这些发现，我们可能会向医生推荐对Plavix无效的患者的潜在替代治疗方案。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study is designed to determine whether the herbal therapy called St. John's wort is effective in enhancing the activity of a drug called clopidogrel (sold under the name Plavix). Plavix inhibits platelet function, much like aspirin. Platelets are tiny cells in your blood stream that clump together to stop bleeding. This clumping is called aggregation and is what normal platelets do. When a person takes Plavix it stops the action of the platelet and thus is called an antiplatelet drug. St. John's wort (not FDA-regulated) is given as an alternative therapy to treat depression. Many medications that are taken, including St. John's wort and Plavix, pass through the liver and require an enzyme called CYP3A4 in order to be metabolized so that the body can use them for the purpose for which they were intended. It is now known that St. John's wort stimulates the production of this liver enzyme CYP3A4. It follows then, that in patients who take Plavix in combination with St. John's wort, we will expect to see an increase effect of Plavix on the platelets. In a recent study we found that not all patients respond to Plavix in the same way. In other words, in some patients it was more effective than in others. The response to Plavix is determined by a blood test that measures percent platelet function, which is the percent of the total platelets that remains functional after Plavix is given orally by mouth. Responders to Plavix will have e70% inhibition of platelet activity post Plavix and low-responders will have <70% platelet inhibitory response to Plavix. In addition to measuring platelet function, we are interested in knowing if, when taking St.John's wort, the activity of this liver enzyme CYP3A4 is actually increased in a measurable amount. Measuring the activity of CYP3A4 will be done with the Erythromycin Breath Test (ERMBT). This study will recruit 100 healthy volunteer adult male and female subjects of any race or ethnicity, aged 18-60. The subjects, who are determined to be responders to Plavix, will be excluded from the study. The subjects who are determined to be low-low responders to Plavix will be included in the study. The primary purpose of the study is to see whether St. John's wort when used in combination with Plavix will increase the antiplatelet action of Plavix. We also want to determine if St. John's wort enhances the liver enzyme CYP3A4 in a measurable amount and will use the ERMBT for that measurement. The secondary purpose is that with these findings, we may be able to make recommendations to physicians on a potential alternative treatment for those patients who do not respond to Plavix.