薬物経皮吸収試験の素材としてのドジョウ摘出皮膚の基礎的検討

概要

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Transdermal permeation of drug across the excised skin of Asian pond loach (Misgurnus anguillicaudatus CANTOR) was studied in vitro. Ten kinds of drugs, D-glucose, L-glucose, sucrose, salicylic acid, cefazolin, urea, antipyrine, naphazoline, propranolol and enviomycin were permeated through the excised loach skin, whereas dextran, a polysaccharide, could not be permeated through the skin. The observed transdermal flux (J), the slope of the line obtained from plots of the cumulative amount of drug permeated vs. time, increased as the drug concentration in the donor compartment solution (50→300mM), as the temperature of the skin (test solution) increased (4→37℃), or as the molecular weight of compound decreased. These results suggested that the transport of drug across the loach skin was due to the passive diffusion mechanism. The effect of pH on the permeation of drug could not be elucidated since the loach skin was drastically impaired below pH 5.0. The J values of antipyrine and naphazoline varied in proportion to the drug concentration in the donor compartment solution at time zero (C_0). The permeability constants (K_p, cm・H^<-1>) of antipyrine and naphazoline were 12.9×10^<-2> and 9.2×10^<-2>, respectively. However, the J values of salicylic acid and urea were not proportional to C_0 in high concentration (300 mM). Probably, these results were related to the irritative effect of salicylic acid or urea on the skin.
1989-09-25