MODULATION OF OPIOID EFFECTS BY GARLIC SUPPLEMENTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 大蒜补充剂经常被癌症患者使用，因为它据称具有增强免疫和抗癌的作用。最近的报道表明，大蒜补充剂可以改变限制药物在肠道吸收的外排药物转运体-P-糖蛋白(PGP)的活性，以及代谢许多药物的一组重要的肝酶--细胞色素P3A(CyP3A)的活性。本研究旨在研究Pgp和CyP3A的这些变化将如何改变阿片类药物羟考酮的止痛和副作用，羟考酮被广泛用于治疗癌症带来的剧烈疼痛。羟考酮在肠道吸收过程中受PGP作用，在代谢过程中受细胞色素P3A4作用。 健康志愿者将被分配到商业大蒜粉制剂(Natural Way大蒜素)或安慰剂片剂的每日治疗中，为期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。为了验证大蒜补充剂确实改变了细胞色素P3A4的活性，我们将研究咪达唑仑的代谢，咪达唑仑是细胞色素P3A4活性的标志，是一种用于使即将接受侵入性医疗程序的人镇静的药物。我们还将研究地高辛的吸收情况，这是肠道PGP的标志，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.