Synthesis of (-)-[4-H-3]epigallocatechin gallate and its metabolic fate inrats after intravenous administration

Because a great deal of attention has been focused on the metabolism of (-) -epigallocatechin gallate (EGCg), quantitative analysis of this compound is required. For this purpose we developed a method of chemical synthesis of [4-H-3]EGCg. Synthesized [4-H-3]EGCg showed 99.5% radiochemical purity and a specific activity of 13 Ci/mmol. To clarify the excretion route of EGCg, the radioactivity levels of bile and urine were quantified after intravenou s administration of [4-H-3]EGCg to bile-duct-cannulated rats. Results showe d that the radioactivity of the bile sample excreted within 48 h accounted for 77.0% of the dose, whereas only 2.0% of the dose was recovered in the u rine. The excretion ratio of bile to urine was calculated to be about 97:3. These results clearly showed that bile was the major excretion route of EG Cg. Time-course analysis of the radioactivity in blood was also performed t o estimate the pharmacokinetic parameters following intravenous administrat ion of [4-H-3]EGCg. In addition, EGCg metabolites excreted in the bile with in 4 h after the intravenous dose of [4-H-3]EGCg were analyzed by HPLC. The results showed that 4',4"-di-O-methyl-EGCg was present in the conjugated f orm and made up about 14.7% of the administered radioactivity.