Studies on the Disposition of TSH-01, a New Transdermal System of Estradiol: Absorption and Plasma Concentration in Rats after a Single Transdermal Application

The absorption and plasma levels of radioactivity were studied in female rats following a single transdermal application of 3H-TSH-01 (3H-labeled estradiol, E2). 1. The plasma levels of radioactivity reached the maximum at 4-8 hr after a single transdermal administration of 3H-E2 and then the radioactivity decreased with T1/2(4-48 hr) of 12.7-17.7 hr. Cmax and AUC increased in a dose-dependent manner within a dose range of 8-32 μg/body. 2. In plasma, the unchanged compound (E2), the main metabolite (estrone) and unknown metabolite were detected by HPLC analysis. The unchanged compound accounted for at least 35% of radioactivity at 24 hr after a single transdermal administration of 3H-E2. 3. The estradiol was mainly detected in the application site of skin after a single transdermal administration of 3H-E2 at 16 μg/body.