1993 Volume 8 Issue 1 Pages 39-47
The absorption, distribution and excretion of ONO-1078(4-oxo-8-[4-(4-phenylbutoxy)benzoylamino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate) were investigated in male beagle dogs.
1. Plasma levels of unchanged drug after oral administration at the doses of 8 or 30mg/kg reached Cmax of 69 and 238ng/ml at 1.7 and 2.7hr after administration, respectively. Significant difference was not observed in T1/2. Bioavailabilities, calculated on the basis of AUC obtained after intravenous administration at the dose of 4mg/kg, were 4.8 and 2.7%, respectively.
2. Plasma levels of radioactivity after oral administration of 14C-ONO-1078 at the dose of 4mg/kg reached Cmax of 28ng eq./ml at 1.3hr after dosing, and declined with T1/2 of 7.2hr. Bioavailability, calculated on the basis of AUC obtained after intravenous administration at the dose of 4mg/kg, was 2.8%.
3. A slight tissue levels of radioactivity at 120hr after oral administration of 14C-ONO-1078 (4mg/kg) were detected in liver, kidney, thyroid gland and blood. No significant level of radioactivity was detected in all other tissues.
4. Within 120hr after oral or intrave nous administration of 14C-ONO-1078 at the dose of 4mg/kg, 99.7 and 99.6% of administered radioactivity were excreted into feces, respectively, indicating fecal excretion was main excretion route in both administration route.
5. Within 48hr after oral administration of 14C-ONO-1078 at the dose of 4mg/kg, 4.9% of administered radioactivity was excreted into bile and 0.3% of administered radioactivity was excreted into urine.
6. ONO-1078 was absorbed from intestinal tract for many hours, and mostly excreted into feces via bile.
