[Studies on the metabolic fate of gomisin A (TJN-101). II. Absorption and excretion in CCl4 treated rats].
The absorption and excretion of gomisin A (TJN-101) in rats whose livers were injured by carbon tetrachloride (CCl4) were investigated. After intravenous administration of TJN-101 at a dose of 5 mg/kg, the terminal elimination half-life was 1.5 h in the CCl4-treated rats, which was two times that in normal rats. The mean area under the blood concentration-time curve (AUC) value of TJN-101 in the CCl4-treated rats was twice that in normal rats, and this difference was significant (p less than 0.05). Therefore, the total body clearance of TJN-101 in the CCl4-treated rats decreased less than half of that in normal rats. Similar results were observed when it was administered orally. In the CCl4-treated rats, the serum concentration of Met. B, which was identified as a demethylenated substance and one of major metabolites, tended to decrease more than that in normal rats. On the other hand, the cumulative biliary excretion ratio of TJN-101 in 24 h after dosing in the CCl4-treated rats was 2.5 times that in normal rats. The excretion rate of Met. B in the bile in the CCl4-treated rats tended to be delayed. However, the quantitative variance of biliary excretion of Met. B was not found in both groups. The urinary excretion of TJN-101 or Met. B in 72 h after dosing in the CCl4-treated rats was lower than that in normal rats. Similar results were also observed in excretion in the feces.(ABSTRACT TRUNCATED AT 250 WORDS)
Matsuzaki
Y
Y
Research Institute for Pharmacology, Tsumura & CO., Ibaraki, Japan.
Matsuzaki
T
T
Ono
H
H
Koguchi
S
S
Takeda
S
S
Takeda
S
S
Funo
S
S
Aburada
M
M
Hosoya
E
E
Oyama
T
T
D000284:Administration, Oral; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D034242:Cyclooctanes; D004149:Dioxoles; D007275:Injections, Intravenous; D017705:Lignans; D008297:Male; D011083:Polycyclic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains
D001798:Blood Proteins; D034242:Cyclooctanes; D004149:Dioxoles; D017705:Lignans; D011083:Polycyclic Compounds; C033585:schizandrol B