The catechol-O-methyltransferase inhibitor, tolcapone, increases the bioavailability of unmethylated (-)-epigallocatechin-3-gallate in mice

(-)-Epigallocatechin-3-gallate (EGCG), has been shown to inhibit cancer in vivo. EGCG, however, is rapidly methylated by catechol-. O-methyl transferase (COMT), which reduces its cancer preventive efficacy. Tolcapone (TOL) is a clinically-used COMT inhibitor. Here, we examined the effect of TOL on the bioavailability of EGCG in male CF-1 mice. Plasma and tissue levels of EGCG and its methyl metabolites were determined following intragastric administration of EGCG (100 mg/kg), TOL (30 mg/kg), or the combination. In mice treated with EGCG, unmethylated plasma EGCG accounted for 63.4% of the total. Co-administration of TOL increased this fraction to 87.9%. In the urine, unmethylated EGCG accounted for 29.2% of the total, whereas treatment with EGCG plus TOL increased this to 81.8%. Similar effects were observed in the major organs examined. TOL effectively inhibited the methylation of EGCG in vivo. Future studies should examine the cancer preventive effects of the combination.