[Concentration-time profile of isosorbide dinitrate and its metabolites in plasma following percutaneous resorption of a transdermal therapeutic system].

Percutaneous absorption of isosorbide dinitrate (ISDN), determined from plasma concentrations of ISDN and its metabolites isosorbide 2-mononitrate (IS-2-MN) and isosorbide 5-mononitrate (IS-5-MN), was studied in 8 healthy subjects aged 19 to 25 years following application of a single plaster containing 40 mg ISDN to the hairless skin on the left side of the chest for 72 h. ISDN and mononitrates were measurable in plasma 2 h after application and maximal concentrations for ISDN and mononitrates occurred after 12-16 h and 16 h, respectively. Mean areas under the curves values corrected for the body surface (BS) (AUC0-72 h.BS of 1074, 815 and 3584 nmol.m2.h/l for ISDN, IS-2-MN and IS-5-MN are equivalent to area ratios of 1, 0.8 and 3.3. ISDN metabolism following transdermal application is less extensive than after oral application. The molar nitrate concentration including metabolites, however, is comparatively low reaching approximately 60-80 nmol/l.