Bioavailability of topically administered steroids: a "mass balance" technique.
Bucks-DA; McMaster-JR; Maibach-HI; Guy-RH
Departments of Pharmacy, Pharmaceutical Chemistry and Dermatology, Schools of Pharmacy and Medicine, University of California, San Francisco, California, 1987 Dec; :1-23
Progesterone (57830), testosterone (58220), estradiol (50282), or hydrocortisone (50237), was applied in acetone to the skin of the ventral forearm of healthy male volunteers. Three procedures were used: covering the application site for the duration of the study; 2, at the end of the dosing period washing the dosed skin surface; and 3, tape stripping the upper layer of stratum corneum when monitoring of urinary excretion was terminated. Such steps enabled the researchers to obtain excellent mass balance and dose accountability measurements. Steroid absorption increased with increasing lipophilicity up to a point, but that penetration of progesterone, which was the most hydrophobic analog studied, did not continue the trend and was at least partly rate limited by slow interfacial transport at the stratum corneum/viable epidermis boundary. Occlusion significantly increased percutaneous absorption of estradiol, testosterone, and progesterone but not hydrocortisone which remained unaffected. The authors suggest that occlusion leads to hydration of the stratum corneum and therefore must exert its effect on the diffusion from the skin surface through the stratum corneum or on the partition from the stratum corneum into the viable epidermis. If hydration decreased the viscosity of the stratum corneum transport system, penetration of all chemicals would be equally enhanced by occlusion. Altering of the stratum corneum/viable epidermis partitioning step is the preferred suggestion.
NIOSH-Grant; Dermatitis; Skin-absorption; Skin-exposure; Pharmaceuticals; Steroids
Pharmacy University of California 926 Medical Sciences Building San Francisco, Calif 94143
57-83-0; 58-22-0; 50-28-2; 50-23-7
Final Grant Report
NTIS Accession No.
Departments of Pharmacy, Pharmaceutical Chemistry and Dermatology, Schools of Pharmacy and Medicine, University of California, San Francisco, California
University of California San Francisco, San Francisco, California