1987 Volume 35 Issue Supplement1 Pages 187-198
Tissue distribution of 14C-6315-S in male and in pregnant rats and its concentration in the milk of lactating rats were investigated after a single or repeated i. v. administration.
Radioactivity was rapidly distributed throughout the body after a single i. v. administration of 20 mg/kg 14C-6315-S, and the highest concentration at 5 min was in the kidney (288.9 μg equivalent of 6315-S/g) followed by plasma (67.2), liver (59.7), lung (36.1), heart (12.5) and other tissues. Thereafter, the levels of radioactivity decreased rapidly to below 1μg/g at 24 h in all tissues tested, indicating that the drug has no tendency to accumulate.
Radioactivity in various tissues shortly after the last dose in repeated administrations (20mg/kg 14C-6315-S once daily for 7 days) was comparable to that after single administra-, tion, but 2-5 times higher at 24 hr after the last dose. However, since its trough level was below 1 μg/g at 168 hr, accumulation obviously did not occur.
Daily excretion of radioactivity in urine and feces under repeated administration was nearly constant: 65% of each dose in urine and 35% in the feces, indicating that the excretion rate was unaffected by repeated administration.
When 14C-6315-S was administered to pregnant rats, less than 5% of the radioactivity found in the maternal plasma appeared in the fetal tissues at 5 min. When 20 mg/kg 6315-S was was administered to lactating rats, the radioactivity in milk was almost the same or lower than that in plasma.
