Effect of skin pretreatment with vehicle alone or drug in vehicle on flux of a subsequently applied drug: results of hairless mouse skin and diffusion cell studies.

Clinical and in vitro evidence suggest that pretreatment of skin with a drug or vehicle can influence topical drug delivery. In this study, hairless mouse skin in diffusion cells was treated for 48 h with topical applications of vehicle alone (oleic acid (OA), isopropyl myristate, octanol (OCT), dimethylformamide, propylene glycol (PG), ethylene glycol (EG), formamide), or mixtures of OA and PG, or with 5-fluorouracil (5-FU) suspensions in each of these vehicles. Twenty-four hours after removing the initially applied agent, a standard suspension of theophylline in PG was applied to the skin surface and the flux of theophylline was determined over the next 48 h. Skin pretreatment with vehicle alone increased theophylline flux 1.6-(EG) to 122-fold (OCT) over control experiments in which the skins were not pretreated. Pretreatment with nonpolar vehicles with lower solubility parameters (OA, OCT, or mixed vehicles containing one of these) had the greatest effect on subsequent theophylline flux. Pretreatment with 5-FU in various vehicles caused a subsequent increased theophylline flux similar to the effect of vehicle alone, except for pretreatment with 5-FU in vehicles which did not have much effect themselves. In those instances, theophylline fluxes up to 16-fold over the effect of those vehicles alone were observed.