Abstract
Distribution and excretion of radioactivity were studied in male rats and male dogs after an intravenous dosing of 14C-FK037 (20 mg/kg).
1. After dosing to rats, plasma and blood levels of radioactivity declined rapidly; the radioactivities at 4 hr after dosing were less than 1% of the concentration at 5 min. The unchanged FK037 in the plasma disappeared two-exponentially with the terminal half-life of 0.43 hr. The ratio of the unchanged FK037 to total radioactivity in the plasma was more than 95% between 5 and 30 min after dosing, and then decreased gradually. The highest levels of radioactivity at 5 min after dosing were detected in the kidney, followed by plasma > blood > lung > liver, heart, spleen> brain. The radioactivities in the tissues, except for the kidney, were not detectable at 24 hr after dosing, and that in the kidney decreased to less than 0.5% of the maximum values. Urinary and fecal excretion of radioactivity was 92.6 and 4.6%, respectively, during 72 hr after dosing. Urinary and biliary excretion of radioactivity in the bile duct-cannulated rats was 98.6 and 1.8 %, respectively within 48 hr after administration. Urinary excretion of the unchanged FK037 was 95.4% during 48 hr, indicating that most of radioactivity in the urine was in the unchanged form.
2. After dosing to dogs, plasma and blood levels of radioactivity declined rapidly; the radioactivities at 8 hr after dosing were about 1 % of the concentration at 5 min. The unchanged FK037 in the plasma disappeared two-exponentially with the terminal half-life of 1.23 hr. The ratio of the unchanged FK037 to total radioactivity in the plasma was more than 97% between 5 min and 2 hr after dosing, and then decreased gradually. Urinary and fecal excretion of radioactivity was 99.8 and 2.4%, respectively, during 168 hr after dosing. Urinary excetion of the unchanged FK037 was 87.7% during 168 hr, indicating that most of radioactivity in the urine was the unchanged FK037.
