title: In vivo relationship between horny layer reservoir effect and percutaneous absorption in human and rat.
abstract: The in vivo relationship between the reservoir effect of the stratum corneum and the percutaneous absorption was established in both human volunteers and hairless rats. Four doses of [ring-14C]benzoic acid, 125, 250, 500, and 1000 nmol, were applied on 1 cm2 either on the external side of the human arm or on the back of the rat, for 30 min. In both human and rat, the data on percutaneous absorption after 4 days is directly related to the dose administered. In rat, the permeability to benzoic acid is twice that of the human skin and the reservoir effect of the stratum corneum, measured at the end of application (30 min), is also doubled for this molecule in rat. Taking into account these findings and the observed histologic differences between the treated areas of these two species, the molecular reservoir of the horny layer may well be situated within the interlayer spaces. For both species, a linear relationship exists between (x), the amount of substance present in the stratum corneum at the end of application (30 min), and (y), the total amount penetrated in 4 days. The relationship, similar to that obtained in an earlier study on rat with 10 molecules, may be written as follows: y = 1.83 x - 0.52 (r = 0.998, p less than 0.001). Thus the amount of substance liable to penetrate through human skin within 4 days can be predicted by measuring the amount present in the stratum corneum 30 min after application of the drug.
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001565:Benzoates / Q000378:metabolism; D019817:Benzoic Acid; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007700:Kinetics; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000378:metabolism / Q000648:ultrastructure; D012869:Skin Absorption
chemical_list: D001565:Benzoates; D019817:Benzoic Acid