Synthesis of (-)-[4-3H]epigallocatechin gallate and its metabolic fate in rats 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-(3)H]EGCg. Synthesized [4-(3)H]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 intravenous administration of [4-(3)H]EGCg to bile-duct-cannulated rats. Results showed 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 urine. 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 EGCg. Time-course analysis of the radioactivity in blood was also performed to estimate the pharmacokinetic parameters following intravenous administration of [4-(3)H]EGCg. In addition, EGCg metabolites excreted in the bile within 4 h after the intravenous dose of [4-(3)H]EGCg were analyzed by HPLC. The results showed that 4',4"-di-O-methyl-EGCg was present in the conjugated form and made up about 14.7% of the administered radioactivity.
Kohri
T
T
Food Research Laboratories, Mitsui Norin Company, Limited, 223-1 Miyabara, Fujieda City, Shizuoka Pref. 426-0133, Japan.
Nanjo
F
F
Suzuki
M
M
Seto
R
R
Matsumoto
N
N
Yamakawa
M
M
Hojo
H
H
Hara
Y
Y
Desai
D
D
Amin
S
S
Conaway
C C
CC
Chung
F L
FL
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D001711:Biotransformation; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D011865:Radioisotope Dilution Technique; D051381:Rats; D017208:Rats, Wistar; D013662:Tea; D014316:Tritium
D000890:Anti-Infective Agents; D013662:Tea; D014316:Tritium; D002392:Catechin; C045651:epigallocatechin gallate