MODULATION OF OPIOID EFFECTS BY GARLIC SUPPLEMENTS

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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. 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.