Analysis of in vitro skin penetration of acyclovir prodrugs based on a diffusion model with a metabolic process

摘要: Abstract The penetration of seven acyclovir prodrugs through the rat skin with or without an enhancer, 1-geranylazacycloheptan-2-one (GACH), was analyzed based on a newly developed two-layer diffusion model polar and nonpolar routes in stratum comeum including metabolic process. Laplace-transformed equations for prodrug regenerated were derived from Fick's second law assuming first-order hydrolysis fitted to experimental data. Under condition GACH treatment, more lipophilic gave higher partition parameters route. enzymatic rate constants estimated by analysis experiment basically similar rank order those obtained using homogenate. Concerning effect GACH, route increased increase pretreatment dose but their diffusivities little affected being good agreement theoretical prediction. In addition, significantly decreased all skin.