Abstract
The absorption, distribution, metabolism and excretion of 14C-dilevalol (Sch-19927) were studied following a 10-day period of daily oral administration to male rats at 30 mg/kg/day.
1. The plasma level of radioactivity at 24 hr after every dosing was below the detection limit until the 5 th dosing and did not increase significantly after the 7 th dosing. The maximal concentration was observed 1 hr after the last dose (5.73 μg equivalent of Sch-19927/ml) and declined with a half-life of 2.53 hr until 8 hr. Most of the radioactivity in the plasma was identified as Sch-19927 glucuronide (M 3).
2. The tissue level of radioactivity reached a plateau by the 5 th dosing. It disappeared more slowly than that after a single dose but accumulation in all tissues except for the testis was low. The testis showed a low accumulation and a residue of radioactivity was due to the unchanged Sch-19927.
3. Repeated administration did not change the excretion profile, and the amount of metabolites excreted during 24-hr to urine after the last dose was similar to that found after a single dose; 77% of the urinary radioactivity was accounted for M 3, with a little of unchanged Sch-19927 and other metabolites being detected.
