Percutaneous Absorption and Excretion of Tritium-Labeled Diflorasone Diacetate, a New Topical Corticosteroid in the Rat, Monkey and Man

The percutaneous absorption and disposition of tritium-labeled diflorasone diacetate (6α,9α-difluoro-16β-methyl-11β,17α, 21-trihydroxypregna-1,4-diene-3,20-dione 17,21-diacetate) was studied in the rat, monkey and man, after a single cutaneous application of the radioactive 0.05% steroid cream. The extent of percutaneous absorption (as measured by excretion) was high in both the rat and monkey, being 88.2% (SD = 6.1%; n=8) and 49.6% (SD = 15.5%; n=4) respectively, of the net administered dose. On the other hand, only 1.1% (SD = 0.5%; n=6) of the net dose was excreted in man, a result compatible with similar data reported for other corticosteroids. The difference may be attributed to anatomical variation in skin structure ( e.g. , greater density of hair follicles and hence increased pilo-sebaceous penetration). Evidence for the retention of the unexcreted diflorasone diacetate in the well-known stratum corneum reservoir was provided by the recovery of small but significant quantities of radioactivity from the surface of the skin of the application sites of all the human volunteers at the termination of the study. The penetration of diflorasone diacetate- 3 H through abnormal skin (abraded to produce hyperemia) was compared with that through normal skin in the animals, but no significant differences were observed except for the prolonged retention of drug-related radioactivity on the abraded skin of the monkeys. The rate of combined urinary and fecal excretion of drug-related radioactivity reached a maximum during the 24–72 hr period after drug administration in the rat and monkey, and during the 48–96 hr period in man. The redistribution of the applied diflorasone diacetate- 3 H radioactivity from the application site to the rest of the skin was observed in the monkey.