title: [Studies on the metabolic fate of gomisin A (TJN-101). II. Absorption and excretion in CCl4 treated rats].
abstract: 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)
authors.affiliation: Research Institute for Pharmacology, Tsumura & CO., Ibaraki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: T
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: H
authors.initials: H
authors.lastname: Ono
authors.forename: S
authors.initials: S
authors.lastname: Koguchi
authors.forename: S
authors.initials: S
authors.lastname: Takeda
authors.forename: S
authors.initials: S
authors.lastname: Takeda
authors.forename: S
authors.initials: S
authors.lastname: Funo
authors.forename: M
authors.initials: M
authors.lastname: Aburada
authors.forename: E
authors.initials: E
authors.lastname: Hosoya
authors.forename: T
authors.initials: T
authors.lastname: Oyama
mesh_terms: 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
chemical_list: D001798:Blood Proteins; D034242:Cyclooctanes; D004149:Dioxoles; D017705:Lignans; D011083:Polycyclic Compounds; C033585:schizandrol B