1987 Volume 2 Issue 3 Pages 199-216
The absorption, distribution, metabolism and excretion of 14C-dilevalol (Sch-19927) were studied following a single oral or intravenous administration to rats.
1. Plasma levels of radioactivity reached a maximal concentration 1 hr after oral administration of 30 mg/kg to male and female rats corresponding to 6.30 and 7.84 μg equivalents of Sch-19927/ml, and then declined with half-lives of 2.59 and 3.22 hr, respectively. A similar profile of plasma radioactivity was obtained at the 10 mg/kg oral dose.
In the in situ experiment, about 30 % of the injected radioactivity was absorbed from the duodenum, jejunum, ileum and rectum but not from the stomach. Most of the radioactivity in the plasma was found to be Sch-19927 glucuronide (M3), with unchanged Sch-19927 accounting for only 1-2 %. The plasma protein binding in vitro was about 60 % and that in vivo was 23 % measured in the plasma samples collected 1 to 6 hr after administration.
After intravenous administration at 10 mg/kg, the half-life of radioactivity in the plasma was 1.2 hr (2 min-4 hr) in both male and female rats. A relatively high proportion of unchanged Sch-19927 was observed in the plasma.
2. The kidney, liver and lung contained high concentrations of radioactivity after oral administration at 30 mg/kg. The radioactivity was cleared from tissues, except the testis, as found with plasma. Though the level was low, the radioactivity in the testis disappeared more slowly than from other tissues. Qualitatively similar tissue distribution was observed by whole-body autoradiography.
3. Male and female rats excreted about 50 % of radioactivity in urine and feces until 120 hr after oral administration at 30 mg/kg. Excretion of radioactivity in bile was 42 % of the dose in males and 57 % in females, with 15 % of the dose entering the enterohepatic circulation. About 80 % of the radioactivity in urine and 40 % in bile were excreted as M3.
