SKIN PERMEATION MODEL OF PHENYLALKYLCARBOXYLIC HOMOLOGOUS ACIDS AND THEIR ENHANCER EFFECT ON PERCUTANEOUS PENETRATION OF 5-FLUOROURACIL

This study was conducted primarily to establish the rat skin penetrati on model of acidic homologous series with a wide range of lipophilicit y (from phenylpropionic acid to phenylcaprylic acid), and to compare i t with other homologous series (allcylanilines) by means of adequate p ermeability-partition correlations, in order to find out if there coul d be a common model of penetration for all the compounds. The influenc e of pH on acid penetration through the skin was also analyzed, Standa rd in vitro skin permeation methods using rat skin were used to determ ine the permeability coefficients of phenylalkylcarboxylic acids in th e conditions established. Membrane/water partition coefficients were a lso assessed, and the correlations between permeability and partition values were established. A linear relationship between the logarithms of permeabilities of penetrants and the corresponding membrane/water p artition coefficients was found. The apparent discordance between this type of correlation and the probabilistic (i.e. parabolic) model prev iously established with other homologous series (alkylanilines) is att ributed to a self-enhancing effect on penetration in the case of the m ore lipophilic compounds of the series. In fact, when S-FU was used as a polar model permeant, pretreatment of the membrane with phenyloenan thic acid gave it an enhancer ratio of 4.5, thus confirming its enhanc er effect.