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

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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.