1997 Volume 12 Issue 1 Pages 5-21
Plasma concentration-time profile, distribution and excretion of ONO-1101 after a single intravenous administration were investigated in male and female rats.
1. AUC0-∞ obtained from plasma levels of radioactivity following intravenous administration of 14C-ONO-1101 at the doses of 0.3, 1, 3, 10 mg/kg to male and female rats, increased approximately in proportion to the dose, and linearity to the dose was observed. The half-life of terminal phase was 27-33 min. There was no difference in the plasma concentration-time profile between male and female rats.
2. Following intravenous administration of 14C-ONO-1101 to male and female rats at the dose of 1 mg/kg, the kidney, liver, lung, trachea, skin and carcass showed high levels or high distribution of radioactivity within 15 min and declined to about or below detection limit in almost all tissues at 24 hr. Radioactivity levels in the brain and fetus were much lower than in the plasma.
3. Following intravenous administration of 14C-ONO-1101 at the dose of 1 mg/kg to lactating rats, the radioactivity in milk reached the highest levels (278.8 ng eq/ml) at 1 hr and then began to decline. At 24 hr the radioactivity in milk was 2.4 ng eq/ml.
4. Within 72 hr after intravenous administration of 14C-ONO-1101 at the dose of 1 mg/kg, 85.6% and 9.9% of administered radioactivity were excreted into urine and feces in male, 84.2% and 12.0% in female rats, respectively.
5. Within 24 hr after intravenous administration of 14C-ONO-1101 at the dose of 1 mg/kg, 6.1% of administered radioactivity were excreted into bile in male, 9.5% in female rats. Sex-difference was observed.
