Disposition of Amorolfine Hydrochloride in Rats —Percutaneous Absorption, Distribution and Excretion after Single Dermal Application—

The absorption, excretion, tissue and dermal distribution of amorolfine were studied following topical application of 0.5 mg of 14C or 3H labelled amorolfine hydrochloride to rat skin. The results were as follows: 1. Blood levels of radioactivity reached the maximum of 6.3 or 9.6 ng eq./ml at 24 hr after application to intact skin, and 91.7 or 19.3 ng eq./ml after application to stripped skin in the form of solution or cream, respectively. 2. Total recovery in urine and feces within 7 days was 5.7 or 5.6% after application to intact skin, and 53.9 or 12.3% after application to stripped skin as the solution or cream, respectively. 3. High levels of radioactivity were observed in the liver, spleen and pancreas at 24 hr after application of the cream to the intact skin, and were retained in the applied dermal site over an extended period. 4. In the microautoradiography of the intact skin at 24 hr after application of cream, the grains distributed uniformly in whole epidermis from stratum corneum to stratum basale, and partially distributed to dermis and hypodermis. 5. The level of radioactivity in sequential skin layers cut in parallel to surface decreased by two semilogarithmic fashions with increasing depth from the surface at 24 hr after application of the cream.