title: [Studies on the metabolic fate of gomisin A (TJN-101). I. Absorption in rats].
abstract: Gomisin A (TJN-101) is one of the lignan components isolated from Schisandra Fruits and expected to have some efficacies in clinical treatment of hepatitis. The serum concentrations of TJN-101 and Met. B, which was identified as a demethylenated substance and one of the major metabolites of TJN-101 in rats, were investigated. After intravenous administration at doses of 1.6, 4.0 and 10 mg/kg of body weight, the serum concentration of TJN-101 decreased biphasically, and the terminal elimination half-life at each dose was about 70 min. Dose-dependency was observed for the area under the concentration-time curve (AUC). On the other hand, the serum concentration of TJN-101 increased rapidly and reached maximum within 15 to 30 min when administered orally. This result was supported by the in situ roop method. The Cmax and the AUC values were not exactly dose-dependent, but the values increased with a dose-up of TJN-101. The biotransformation of TJN-101 to Met. B, was very rapid in both intravenous and oral administrations. The AUC value of Met. B after oral administration of TJN-101 at a dose of 1.6 mg/kg was relatively larger than any other dosages. It suggested that TJN-101 was extensively underwent the first pass effect in rats. More than 80% of TJN-101 was bound with rat serum protein in vitro and in vivo. Therefore, it seems to be necessary to pay attention when it was administered concurrently with high protein binding drugs.
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: S
authors.initials: S
authors.lastname: Takeda
authors.forename: S
authors.initials: S
authors.lastname: Koguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeya
authors.forename: H
authors.initials: H
authors.lastname: Mitsuhashi
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
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; D002851:Chromatography, High Pressure Liquid; D034242:Cyclooctanes; D004149:Dioxoles; D007275:Injections, Intravenous; D007408:Intestinal Absorption; 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