Bioavailability and metabolism of isosorbide dinitrate from a transdermal spray.

The plasma pharmacokinetics of isosorbide dinitrate (ISDN), isosorbide-2-nitrate (IS-2-N) and isosorbide-5-nitrate (IS-5-N) were investigated in 12 healthy volunteers after a single cutaneous administration of 60 mg ISDN (CAS 87-33-2) in the form of a solution sprayed onto the skin (TD Spray Iso Mack), in comparison with an intravenous infusion of 5 mg ISDN. After the intravenous dose, the apparent steady state volume of ISDN distribution came to 179.9 l, total body clearance was 3.14 l min-1, and terminal half-life was 79 min, on average. The transdermal absorption resulted in an average peak plasma concentration of 6.9 ng ISDN ml-1 at 5 h after the administration. ISDN concentrations between 1 and 5 ng ml-1 were maintained over at least 15 h. On average, 16.5% of the topically applied ISDN reached the systemic circulation. Total variations in Cmax (CV = 47.9%) and AUC (CV = 36.0%) of transdermal ISDN were similar to those usually observed after oral ISDN.