Matsuzaki Y, Matsuzaki T, Ono H, Koguchi S, Takeda S, Takeda S, Funo S, Aburada M, Hosoya E, Oyama T
Research Institute for Pharmacology, Tsumura & CO., Ibaraki, Japan.
Yakugaku Zasshi. 1991 Sep;111(9):531-7. doi: 10.1248/yakushi1947.111.9_531.
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)
研究了四氯化碳（CCl4）损伤肝脏的大鼠对戈米辛A（TJN-101）的吸收和排泄情况。以5mg/kg的剂量静脉注射TJN-101后，CCl4处理组大鼠的末端消除半衰期为1.5小时，是正常大鼠的两倍。CCl4处理组大鼠中TJN-101的血药浓度-时间曲线下平均面积（AUC）值是正常大鼠的两倍，且差异具有统计学意义（p小于0.05）。因此，CCl4处理组大鼠中TJN-101的全身清除率降低至正常大鼠的一半以下。口服给药时也观察到了类似结果。在CCl4处理组大鼠中，被鉴定为去亚甲基化物质且是主要代谢产物之一的Met.B的血清浓度下降趋势比正常大鼠更明显。另一方面，CCl4处理组大鼠给药后24小时内TJN-101的累积胆汁排泄率是正常大鼠的2.5倍。CCl4处理组大鼠胆汁中Met.B的排泄速率趋于延迟。然而，两组中Met.B的胆汁排泄量均未发现定量差异。CCl4处理组大鼠给药后72小时内TJN-101或Met.B的尿排泄量低于正常大鼠。粪便排泄情况也观察到了类似结果。（摘要截短至250字）
