Abstract
During the course of biochemical studies on drug metabolisms in injured liver, a new technique for determining FT-207 in blood and liver was developed by using a high pressure liquid chromatography. The pharmacodynamics of FT-207 was analysed by measuring its disappearance rate (K) from the circulating blood. Since K values vary depending upon the dose of FT-207 administered, a constant dose was intravenously or orally given to rats (100mg/kg body weight) and human subjects (ca.16mg/kg). The alterations of K values in rats pretreated for 3 days with phenobarbital or indometacin suggested that the disappearance rates seemed to be well correlated with the activity of drug-metabolizing enzymes in liver microsomes. Inhibition of 3H-uridine incorporation into liver RNA by FT-207 was unchanged upon pretreatment of rats with phenobarbital and indometacin. Clearances of FT-207 from blood were much slower in hepatoma patients with cirrhosis of the liver than malignant cases without liver impairement. The results may be consistent with the fact that FT-207 levels in blood tended to gradually increase with the daily oral administration in cases with liver diseases as compared with those without hepatic dysfunction.
