MODULATION OF OPIOID EFFECTS BY GARLIC SUPPLEMENTS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 大蒜补充剂经常被癌症患者使用，因为它具有增强免疫力和抗癌作用。 最近的报告表明，大蒜补充剂可以改变一种外排药物转运蛋白-P-糖蛋白（Pgp）的活性，限制药物的肠道吸收，以及一组重要的肝酶-CYP 3A的活性，代谢许多药物。 本研究旨在研究Pgp和CYP 3A的这些变化将如何改变阿片类药物羟考酮的疼痛缓解和副作用，羟考酮广泛用于治疗癌症引起的严重疼痛。 羟考酮在其肠道吸收过程中受Pgp作用，在其代谢过程中受CYP 3A 4作用。 健康志愿者将被分配到每天使用商业大蒜粉制剂（Nature Way Garlicin）或安慰剂片剂治疗4周。 我们将研究参与者在服用大蒜片和安慰剂片时如何吸收和代谢羟考酮。 我们还将评估羟考酮缓解疼痛和伴随的副作用的能力。 为了检查大蒜补充剂确实改变了CYP 3A 4的活性，我们将研究咪达唑仑的代谢，咪达唑仑是CYP 3A 4活性的标志物，是一种用于镇静即将接受侵入性医疗程序的人的药物。 我们还将研究地高辛的吸收，地高辛是肠道Pgp的标志物，也是一种广泛用于治疗充血性心力衰竭的药物。

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. Garlic supplement is frequently used by cancer patients for its purported immune enhancement and anticancer effects. Recent reports suggest that garlic supplements can modify the activity of an efflux drug transporter-P-glycoprotein (Pgp) that limits intestinal absorption of drugs, as well as the activity of an important group of liver enzymes-CYP3A that metabolizes many drugs. The present study is designed to investigate how these changes in Pgp and CYP3A will change the pain relief and side effects of an opioid medication oxycodone, which is widely used to treat severe pain from cancer. Oxycodone is acted upon by Pgp during its intestinal absorption and by CYP3A4 during its metabolism. Healthy volunteers will be assigned to either daily treatment with a commercial garlic powder preparation (Nature Way Garlicin) or a placebo tablet for a period of 4 weeks. We will study how the participants absorb and metabolize oxycodone while taking the garlic tablet and while taking the placebo tablet. We will also assess oxycodone's ability to relieve pain and attendant side effects. To check that the garlic supplement indeed changed the activity of CYP3A4, we will study the metabolism of midazolam, which is a marker for the activity of CYP3A4 and is a drug used to sedate people about to undergo invasive medical procedures. We will also study the absorption of digoxin, which is a marker for intestinal Pgp and a drug widely used to treat congestive heart failure.