Diclofenac metabolic profile following in vitro percutaneous absorption through viable human skin

The extent of metabolism of diclofenac sodium in excised viable human skin was investigated using combination HPLC and radioactivity assay. In an earl ier diffusion experiment using an in vitro flow-through diffusion system, r adiolabelled diclofenac sodium in either lotion (Pennsaid(PR)) or aqueous s olution was applied to viable human skin, either as single dose or multiple dose (8 times over 2 days). In this study, the receptor fluid samples from the diffusion experiment were subjected to extraction and the aliquot was analysed using HPLC to separate diclofenac and authentic metabolites. Based on the radioactivity of each HPLC fraction, the collection time of the fra ctions was compared with the retention time of diclofenac and metabolites i n standard solutions. The samples from a single or multiple dose applicatio n of lotion showed radioactivity in mainly one fraction, whose retention ti me corresponded with diclofenac. Other HPLC fractions showed none or only s mall amounts of radioactivity within the error range of the assay. The same results were obtained with the pooled samples from the application of the lotion or of aqueous solution. The results suggest that diclofenac sodium d oes not undergo metabolism in viable human epidermis during percutaneous ab sorption in vitro. Hence, with topical application to human skin in vivo, d iclofenac will be delivered with minimal, if any, metabolism.