Nishida M, Murakawa T, Okada N, Sakamoto H, Yokota Y
Chemotherapy. 1977;23(6):416-23. doi: 10.1159/000222011.
Serum levels of FR10612 given orally to rats persisted significantly longer than did those of cephalexin. Since the elucidation of this phenomenon observed in rats is considered to be pertinent to the understanding of the drug kinetics of FR10612 in other animals including man, the present study was undertaken. From the dose-response curve of the serum levels of FR10612 in rats, it is apparent that the maximum oral absorption is obtained in the range of 100-400 mg/kg. Even when the doses were increased from 100 to 1,000 mg/kg, the tissue levels with the exception of the kidneys, did not increase significantly. However, the persistence of the tissue levels was enhanced. The serum and tissue levels of FR10612 in rats after repeated massive dosings did not increase accumulatively. From the experimental results of FR10612 in rats with ligated bile ducts and the results obtained after intravenous injection, it seems clear that the prolonged in vivo levels of FR10612 in rats after oral dosing are closely related to its enterohepatic circulation.
给大鼠口服后，FR10612的血清水平持续时间明显长于头孢氨苄。由于在大鼠中观察到的这一现象的阐明被认为与理解FR10612在包括人类在内的其他动物中的药物动力学相关，因此开展了本研究。从大鼠中FR10612血清水平的剂量反应曲线来看，显然最大口服吸收量在100 - 400 mg/kg范围内。即使剂量从100 mg/kg增加到1000 mg/kg，除肾脏外的组织水平并未显著增加。然而，组织水平的持续时间延长了。多次大剂量给药后大鼠体内FR10612的血清和组织水平并未累积增加。从FR10612在胆管结扎大鼠中的实验结果以及静脉注射后获得的结果来看，口服给药后大鼠体内FR10612水平的延长似乎与其肝肠循环密切相关。
