THE ROUTES OF PENETRATION OF IONS AND 5-FLUOROURACIL ACROSS HUMAN SKIN AND THE MECHANISMS OF ACTION OF TERPENE SKIN PENETRATION ENHANCERS

The activation energies for ion movement and 5-fluorouracil diffusion across human epidermis in vitro have been measured to be 4.08 +/- 0.16 and 20.6 +/- 1.56 (mean +/- SE) kcal mol-1, respectively. These data imply that ions travel across human epidermis largely through aqueous shunt routes and that 5-fluorouracil, a polar non-electrolyte, travels mainly through the intercellular lipid bilayers in the stratum corneu m. Treatment of human epidermis with terpene penetration enhancers has been shown to increase electrical conductivity. The increase in ion t ransport suggests that terpenes open new polar pathways across the str atum corneum. A correlation between increases in ion transport and pre viously reported increases in 5-fluorouracil penetration suggests that terpene enhancers may create micro-pores in the intercellular lipids through which both ions and polar drugs may pass.