ymes in a Healthy Volunteer Study

nloaded veratrol has been shown to exhibit cancer-preventive activities in preclinical studies. We cona clinical study to determine the effect of pharmacologic doses of resveratrol on drugand ogen-metabolizing enzymes. Forty-two healthy volunteers underwent baseline assessment of rome P450 (CYP) and phase II detoxification enzymes. CYP1A2, CYP2D6, CYP2C9, and CYP3A4 e activities were measured by the metabolism of caffeine, dextromethorphan, losartan, and bus, respectively. Blood lymphocyte glutathione S-transferase (GST) activity and GST-π level and total and direct bilirubin, a surrogate for UDP-glucuronosyl transferase (UGT) 1A1 activity, were red to assess phase II enzymes. After the baseline evaluation, study participants took 1 g of atrol once daily for 4 weeks. Enzyme assessment was repeated upon intervention completion. atrol intervention was found to inhibit the phenotypic indices of CYP3A4, CYP2D6, and CYP2C9 induce the phenotypic index of 1A2. Overall, GST and UGT1A1 activities were minimally affectthe intervention, although an induction of GST-π level and UGT1A1 activity was observed in duals with low baseline enzyme level/activity. We conclude that resveratrol can modulate enzyme s involved in carcinogen activation and detoxification, which may be one mechanism by which atrol inhibits carcinogenesis. However, pharmacologic doses of resveratrol could potentially lead reased adverse drug reactions or altered drug efficacy due to inhibition or induction of certain CYPs. to inc Further clinical development of resveratrol for cancer prevention should consider evaluation of lower doses of resveratrol to minimize adverse metabolic drug interactions. Cancer Prev Res; 3(9); 1168–75. ©2010 AACR.