Cutaneous metabolism of isosorbide dinitrate after transdermal administration in isolated perfused porcine skin

The purpose of this study was to determine whether isosorbide dinitrate (ISDN) was metabolized by the skin during transdermal delivery. In order to assess this, the isolated perfused porcine skin flap (IPPSF) was utilized since this in vitro model possesses a viable epidermis and intact vasculature, two attributes ideal for studying the biotransformation of a vasoactive drug. ISDN transdermal systems (20 cm(2)) were applied onto IPPSFs and the venous efflux sampled repeatedly over 16 h. ISDN, isosorbide-2-mononitrate (IS-2-MN), and isosorbide-5-mononitrate (IS-5-MN) fluxes were determined using gas chromatography. Approximately 14% of parent ISDN was metabolized to IS-2-MN and 10% to IS-5-MN. These observations are important as they indicate that a fraction of ISDN is biotransformed during transdermal delivery.