Enterohepatic circulation of a new oral cephalosporin, FR10612, and its effect on serum and tissue levels in rats

Abstract

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.