Melatonin is an endogenous hormone administered in supraphysiologic doses for promoted uses of antioxidant, antiaging, contraception, adjunct therapy with cancer chemotherapy, and treatment of sleep disorders. Despite its widespread use, there are no data regarding the potential for drug interactions. The purpose of this study is to determine the effect of administration of melatonin for 1 week on the activity of cytochrome p450 1A2, 2D6, 3A4, NAT2, and Xanthine Oxidase (XO). Fifteen healthy volunteers will undergo enzyme activity phenotyping by ingesting 2 mg/kg of caffeine and 30 mg of dextromethorphan followed by an overnight urine collection on five occasions. Subjects will take, in a randomized, crossover design, 3 mg of melatonin at bedtime for 1 week and ketoconazole 200 mg once daily for 5 days each separated by a one-week washout period. Beginning the evening before and following each course of therapy, subjects will undergo enzyme activity phenotyping again as described above. Enzyme activity following 7 days of melatonin will be compared with pre-treatment values to characterize the magnitude of inhibition of cytochrome p450 1A2, 2D6, 3A4, NAT2, and XO activity.
