AGING AND CYP-MEDIATED HERB-DRUG INTERACTIONS

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Adverse drug effects stemming from hepatic cytochrome P-450-mediated drug interactions are prevalent in the elderly. With the widespread use of herbal dietary supplements, potential herb-drug interactions are also emerging as a significant medical concern. It has been estimated that nearly 1 in 5 individuals taking prescription medications also take herbal supplements. This translates to more than 15 million adults, including nearly 3 million adults aged 65 years or older, who take prescription medications concurrently with herbal supplements. Furthermore, it has been noted that 70 percent of patients do not reveal their herb use to primary care providers. The risk of potential herb-drug interactions, therefore, is considerable. This is especially so in the elderly who not only receive multiple medications, but often exhibit reduced hepatic drug clearance. Documented herb-drug interactions are increasingly reported in the medical literature, and while a few in vitro studies indicate that the phytochemical components of botanical medicines can modulate hepatic drug metabolizing enzymes (cytochrome P-450s, CYP), no prospective studies into the mechanisms underlying such interactions have been conducted in humans. The hypothesis to be tested in this investigation is that elderly patients are at an increased risk for herb-drug interactions secondary to herb-mediated changes in hepatic CYP enzyme activity. The current proposal will utilize parent/metabolite ratios of phenotypic probe drugs to assess the effect chronic herbal supplementation has on hepatic CYP activity in human volunteers of varying age. The goals of this project are: (1) to determine if chronic usage of dietary supplements containing either garlic, gingko biloba, ginseng, or St. John's wort modulate specific hepatic CYP activities (i.e. CYP1A2, CYP2D6, CYP2E1, and CYP3A4); and (2) whether aging potentiates the risk of CYP-mediated herb-drug interactions.