1990 Volume 5 Issue 6 Pages 883-902
The absorption, distribution and excretion of betamethasone butyrate prop ionate (BBP) were investigated in rats and rabbits after dermal application of 3H-BBP under non-occlusion or subcutaneous administration of 3H-BBP at a dose of 0.25 and 1.0mg/kg, respectively.
1. The systemic availability after dermal application of 3H-BBP, as ointment or cream to normal skin of animals was low, accounting for ca. 3 ?? 5% of the applied dose in male rats and ca. 14% in female rats and male rabbits. The availability from stripped skin was ca. 30 ?? 50% in rats.
2. The maximum blood concentration of radioactivity and its appearance time after dermal application to normal skin of animals were : 0.6 ?? 0.8ng/ml and 24hr in male rats, 4.7ng/ml and 8 hr in female rats, and 3.0ng/ml and 13hr in male rabbits. These values were 8.6 ?? 15.7ng/ml and 5hr in stripped skin of male rats.
3. Most of the radioactivity administered dermaly was excreted with feces in rats, while equally excreted with urine and in rabbits.
4. The maximum tissue radioactivity was observed at 8 or 24hr after dermal application to intact skin of male rats. High levels of radioactivity were noted in the liver, kidney, adrenal gland, seminal vesicle and urinary bladder. The disappearance of radioactivity from each tissue was slow, especially from blood. The microautoradiogram of application site of skin showed the routes of dermal absorption of BBP via appendage and through epidermis.
5. After the repeated dermal application to intact skin of male rats, blood and tissue radioactivity at 24hr after daily application rose with increasing of dosing times. After the 7th dermal application, the disappearance of radioactivity from the blood and tissues was slow and the radioactivity concentration in the blood, 54 days after dermal application, was 15% of the maximum radioactivity concentration. No difference of the excretion of radioactivity in the urine and feces was noted between the 7th dermal application and single application groups.
6. The placental transfer of 3H-BBP after subcutaneous administration was confirmed by whole body autoradiogram in pregnant rats, but no radioactivity remained in the fetal tissue.
