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The influence of drug partition coefficient on follicular penetration: in vitro human skin studies

Frum, Y. and Bonner, M. and Eccleston, G.M. and Meidan, V.M. (2007) The influence of drug partition coefficient on follicular penetration: in vitro human skin studies. European Journal of Pharmaceutical Sciences, 30. pp. 280-287. ISSN 0928-0987

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Abstract

The aim of this study was to employ the novel skin sandwich system in order to quantify the influence of the octanol-water partition coefficient on follicular drug absorption in human skin. To this end, seven different drugs - estradiol, corticosterone, hydrocortisone, aldosterone, cimetidine, deoxyadenosine and adenosine - exhibiting a wide range of log octanol-water partition coefficients (logK0/w) but relatively similar molecular weights were selected as candidate solutes. Application of the skin sandwich technique yielded an interesting relationship between % follicular contribution and logKo/w The follicular contribution to total flux was small (4 and 2%) for the two most lipophilic drugs but varied between 34 and 60% for the remaining drugs of intermediate and low logKo/w values. Lipophilicity seems to be an important modulator of drug absorption into follicular orifices only above a critical logKo/w threshold. Below this critical logKo/w value, lipophilicity does not apparently influence the follicular contribution in an obvious way and the process is probably governed by other molecular properties. Identification of these other active properties would require performing this kind of a study on a much larger set of candidate drugs.