Studies on the metabolic fate of FO-1561 in rats. (II). Blood and plasma levels, distribution and excretion after intravenous administration of (CH3-14C)FO-1561.

Abstract

The blood and plasma levels, distribution and excretion of S-adenosyl-L-methionine sulfate tosylate (FO-1561) were studied in rats afer intravenous administration of [CH3-14C] FO-1561. 1. After intravenous administration of 10 mg/kg to rats, the blood and plasma levels of radioactivity decreased biphasically until 2 hr, and then kept steady state until 24 hr. After intravenous administration of 100 mg/kg to rats, the blood and plasma levels of radioactivity decreased biphasically until 4 hr, increased slightly until 8 hr, and then decreased slowly. The biological half life of radioactivity at early time period after administration was slightly shorter in plasma than in blood. The dose dependence in the biological half life was not observed. 2. The main excretory route of radioactivity was in urine (31.30 %) and expired air (29.72 %) at a dose of 10 mg/kg, and in urine (74.39 %) at a dose of 100 mg/kg. The excretion of radioactivity in feces or bile was slight. At 120 hr after administration, the residual of radioactivity in carcass was 33.41 % of dose in the group administered at 10 mg/kg, and 11.39 % of dose in the group administered at 100 mg/kg. 3. At 6 hr after administration, the increase of radioactivity was observed in the gastro-intestinal wall and several tissues, and in the skeletal muscle at 48 hr. These results suggest that [CH3-14C] may be incorporated into endogenous substance. The high level of radioactivity in the kidney was observed during 120 hr after administration. 4. The binding of radioactivity to plasma protein increased gradually after 1 hr and at 24 hr later, more than 90 % of radioactivity was bound to protein. The binding of radioactivity to blood cell increased gradually after 6 hr, and the binding rate of radioactvity was 69.64 % at 120 hr.