Distribution and Metabolism of Sphingosine in Skin after Oral Administration to Mice

In this study, (3)H- or (13)C(2),D(2)-sphingosine (SPH) was orally administered to mice to assess absorption, mass balance, tissue distribution, and metabolites in the skin The blood concentration of (3)H-SPH showed a Tmax of 10 7 hr The radioactivity in the skin reached 763 4 ng eq /g tissue at 12 hr, and decreased to 181.7 ng eq /g tissue at 168 hr. The concentration of radioactivity at 12 hr was 577 6 and 100 7 ng eq /g tissue in the dermis and epidermis, respectively Thereafter, the dermis concentration decreased to 158 5 ng eq /g tissue, while the epidermis concentration increased to 298 8 ng eq /g tissue, suggesting that radioactivity moves from the dermis to the epidermis Unchanged SPH along with lipophilic metabolites was detected in the skin of mice exposed orally to (3)H- or (13)C(2),D(2)-SPH Moreover, in an in vitro study using human skin keratinocytes, a (13)C(2,)D(2)-SPH-treatment resulted in the intracellular production of glucosylceramides (GlcCer) and ceramides (Cer) containing labeled-SPH These results indicate the followings first, that SPH is absorbed through the digestive tract and distributed to the skin, second, it is transferred from the dermis to the epidermis. and third, SPH is partly distributed to the skin in an unchanged form, and some of the distributed compounds are converted into GIcCer and Cer by biosynthesis