EFFECT OF VEHICLES ON PERCUTANEOUS-ABSORPTION OF BUCLADESINE (DIBUTYRYL-CYCLIC-AMP) IN NORMAL AND DAMAGED RAT SKIN

Bucladesine, sodium N-6,2'-O-dibutyryl cyclic 3',5' adenosine monophos phate (DBcAMP), which is effective for the treatment of chronic skin u lcers including decubitus ulcer, was evaluated for percutaneous absorp tion in rats with normal skin, stripped skin and full-thickness abrasi on models. Percutaneous absorption from aqueous solution or ointment w as very low in intact skin. When the aqueous solution was applied to t he site where the skin had been excised, DBcAMP was absorbed very rapi dly and almost completely. In the case of stripped skin, DBcAMP was ab sorbed rapidly but slower than in the full-thickness abrasion model. I n both damaged skin models, a better absorption profile was obtained w ith the polyethylene glycol (PEG) than the petrolatum ointment and DBc AMP was released continuously from the PEG ointment, indicating that t his ointment is suitable for the treatment of ulcers of the skin. The percutaneous absorption from stripped skin was considerably influenced by the powder formulation. It is appropriate to evaluate the bioavail ability in damaged skin models for a drug, such as DBcAMP, which is us ed in the treatment of skin ulcer.