Rotating-disk method for determining cutaneous metabolism.

Since design and evaluation of topical dosage forms should account for both skin permeation and cutaneous metabolism, an in vitro system was formulated to determine the metabolic component of viable guinea pig skin utilizing the diffusion layer property of the rotating disk. The drug investigated was vidarabine, an antiviral agent, which was rapidly metabolized to 9-beta-D-arabinofuranosylhypoxanthine. The aqueous diffusion coefficient of the drug was determined by the capillary cell method. The rotating-disk system was standardized using benzoic acid. The dorsal skin of a guinea pig was removed after shaving, and the epidermal section was excised by a keratome. After the section was mounted on the stainless steel disk with a tissue adhesive, the preparation was immersed in a 10-ml beaker containing 5 ml of drug solution at 37 degrees. At suitable intervals, samples were withdrawn, separated by TLC, and assayed by liquid scintillation. The enzyme rate constant was 1.54 x 10(-1) sec-1.