Abstract
Plasma concentration-time profile, distribution and excretion of ONO-1101 after repeated intravenous administration were investigated in rats. Also the influence on the hepatic drug metabolizing enzyme activities was examined.
1. The radioactivity in plasma at 24 hr after each intravenous administration of 14C-ONO-1101 at the dose of 1 mg/kg/day for 7 days was not detected or was around the detection limit. Repeated administration had no effect on plasma concentration-time profile.
2. Following repeated intravenous admini stration of 14C-ONO-1101 to male rats at the dose of 1 mg/kg, the kidney, liver, lung, trachea contained high levels of radioactivity that declined to about or below detection limit in almost all tissues at 24 hr. Also in skin and carcass, a high degree of radioactivity were observed within 15 min then declined. Compared with a single administration, the elimination of radioactivity in kidney and liver was slightly delayed. But repeated intravenous administration was not associated with any accumulation of radioactivity in organ or tissue.
3. The daily excretion of radioactivity in urine and feces was constant since 4-th administration. After repeated intravenous administration, the excretion of radioactivity into urine and feces was respectively 89.7, 14.9%, for male, 86.5, 17.0% for female rats.
4. Repeated intravenous administration of ONO-1101 at the doses of 1, 10, 50 mg/kg/day for 7 days had no effect on microsomal protein content, liver weight and hepatic drug metabolizing enzyme activities.
