1987 Volume 2 Issue 3 Pages 237-246
The absorption, metabolism and excretion of 14C-dilevalol (Sch-19927) were studied following a single or a 10 day period of daily oral administration to dogs at 30 mg/kg.
1. The plasma levels of radioactivity reached a peak level (15.22 μg equivalent of Sch-19927/ml) 2 hr after a single dosing and declined with a half-life of 4.43 hr until 8 hr. Two hours after dosing, 26 % of the radioactivity in the plasma was due to unchanged Sch-19927, 40 % was MD1 and 25 % was M3.
The in vitro plasma protein binding experiments showed that Sch-19927 was bound in more than 90 % at 0.1 and 1 μg/ml but about 60 % at 10 μg/ml concentrations in dog plasma.
The in vivo binding was 35 and 69 % determined in the plasma samples collected 2 and 24 hr ather administration, respectively.
2. Excretion of radioactivity was 66 % of the dose in urine and 32 % in feces by 120 hr after single dosing. Of the urinary radioactivity, 6 % was unchanged Sch-19927, 52 % MD1 and 18 % M3. MD1 and M3 were assumed to be alcoholic and phenolic glucuronides of Sch-19927, respectively.
3. During repeated administration, the plasma level at 24 hr after every dosing showed no marked change. It reached a peak level (16.99 μg equivalent of Sch-19927/ml) at 1.5 hr after the last dose and declined more slowly than after single dosing witn a half-life of 7.12 hr until 8 hr. Two hours after repeated dosing, 32 % of the radioactivity in the plasma existed as unchanged Sch-19927, 28 % as MD1 and 17 % as M3.
4. Within 120 hr after the last dose, the excretion radioactivity in urine was 65 % of the dose and that in the feces was 31 % of the dose. This urine had proportions of unchanged Sch-19927 and metabolites similar to those found after single administration.
