| Popis: |
The absorption, distribution, metabolism and excretion of MC903 were investigated in rats after a single dermal application in 5 μg/100 mg ointment/body using an occlusive dressing technique. 1. The radioactivity level in the plasma reached a Cmax at 24 hr, and there after decreas ed with a t1/2 (48-168 hr) of 2.9 days in male rats with an intact skin. In male rats with a stripped skin, the Cmax and AUC(0-∞) were 23 and 6.9 times higher than those with an intact skin, respectively. In female rats with an intact skin, the t1/2 and AUC(0-∞) were 4.5 and 4.1 times, respectively, higher than in male rats. 2. In male rats with an intact skin, the radioactivity levels in tissues examined gradually increased, and reached maximal levels between 24 and 96 hr. The elimination of radioactivity from tissues was slow. The whole body autoradiograms showed high levels of radioactivity in the application site of skin and in the gastro-intestinal content. The microautoradiogram of the skin showed that 3H-MC903 was absorbed mainly through the horny layer. 3. Total recovery of radioactivity in male rats with an intact skin within 168 hr was 2.0, 13.3 and 0.6% in urine, feces and in expired air, respectively. In male rats with a stripped skin, the excretion rates of radioactivity increased as compared with those of male rats with an intact skin. In female rats with an intact skin, the excretion rates of radioactivity increased as compared with those of male rats. 4. The unchanged drug was mainly detected in the application site of skin and in muscle layer under the skin. |
