Abstract
The absorption, distribution and excretion of [3, 4-di(4-methoxyphenyl)-5-isoxazolyl] acetic acid (mofezolac) were studied in rats after a single or repeated oral administration of 14C-labeled-mofezolac.
1. Concentration of radioactivity in the blood increased rapidly after oral administration, reaching Cmax within 15min, and decreased to 1.4% of the maximum level 12hr after administration.
2. Approximately 55% and 39% of radioactivity were excreted during 72hr after administration in urine and feces, respectively.
3. About 62% of radioactivity was excreted in bile. When the bile was administered, about 52% of radioactivity present in the bile was re-absorbed. This result suggested the presence of the entero-hepatic circulation.
4. Tissue radioactivity was higher in the stomach, liver and kidney, while the radioactivity in other tissues was lower than that in plasma. Radioactivity disappeared rapidly from any tissue.
5. When female rats were administered 14C-mofezolac on day 11 or 18 of pregnancy, or slight radioactivity usually lower than in maternal plasma was observed in the fetus. Radioactivity in fetus as well as in maternal tissues disappeared rapidly. Radioactivity in the fetus was not detected at 24hr after administration.6. Concentration of radioactivity in the milk at 2hr after administration to lactating rats reached levels about 5 times higher than that in plasma, however the radioactivity in milk was not detected at 48hr.
7. In case of repeated administration of 14C-mofezolac for 7 days, the disposition of radioactivity was almost same as the result after a single dosing, and radioactivity scarcely remained in any tissues after the last administration.
