Influence of the size of the area of treatment on percutaneous absorption of estradiol in the rat.

Abstract

The influence of the dose, as well as the application area of topically applied 3H-estradiol in a volatile solution on its systemic bioavailability was investigated in hairless rats in vivo. The bioavailability was determined by comparing the urinary and fecal excretion of radioactivity after intravenous injection and after topical application. Whatever the size of the surface of application (1, 4 or 16 cm2), the bioavailability was similar (47-65%) 4 days after the application of a single low dose (50 nmol). When the surface of application was washed 24 h after dosing, the absorption was the same for the areas of 3 and 9 cm2. In all cases average fluxes on the first day were higher for the larger area. When applied doses were increased (1,000 and 10,000 nmol), the percentage of percutaneous absorption decreased with the reduction in the areas of application. Thus, with a dose of 1,000 nmol applied on a surface of 1, 4 and 16 cm2, absorption was equal to 18.7, 21 and 37%, respectively, of the dose. There was a linear relationship between the log of the dose applied per unit of skin area and the percentage of absorption after 4 days (r = 0.99 with washing; r = 0.98 without washing).(ABSTRACT TRUNCATED AT 250 WORDS)