Alternative or complementary therapies are widely used by patients with epilepsy. St. John?s Wort is one of the most popular herbal dietary supplements, with a variety of claims including mood elevation and stabilization, stress relief, antiviral effects, and enhancement of the immune system. Recent preliminary data suggest that St. John?s Wort is a potent inducer of cytochrome P-4503A4-mediated drug metabolism. Carbamazepine shares this metabolic pathway, suggesting that plasma concentrations of carbamazepine may be decreased during concomitant use. Such an effect could result in treatment failure (increased seizure frequency, loss of pain relief). To evaluate this potential drug interaction, as well as the effect of St. John?s Wort on epoxide hydrolase activity, eight normal, healthy subjects will be enrolled in this pharmacokinetic study. Subjects will take carbamazepine for 3 weeks to establish steady state conditions. Serial blood samples for carbamazepine and carbamazepine epoxide plasma concentrations will be collected over 24 hours following 3 weeks of dosing. Subjects will then begin taking a standardized formulation of St. John?s Wort three times daily for 2 weeks. During this period, subjects will continue to take carbamazepine. Following 2 weeks of St. John?s Wort, subjects will again have serial blood samples collected for carbamazepine and carbamazepine epoxide plasma concentrations. The total carbamazepine and carbamazepine epoxide exposure as measured by area under the plasma concentration time curve (AUC) and maximal concentrations (Cmax) will be compared between treatment phases to characterize the potential drug interaction.
