Percutaneous absorption of 1,3-dinitroglycerin and a trial of pharmacokinetic analysis

In order to estimate the pharmaceutical usefulness of 1,3-glyceryl dinitrate (1,3-GDN), an active metabolite of nitroglycerin, a trial transdermal delivery system designed to sustain a suitable plasma concentration of 1,3-GDN was produced using a porous membrane (Hipore 2100 or 4500) and it was a gel base or ethylhexyl acrylate-based adhesive (adhesive) and it was applied to rats. Additionally, for practical use of the transdermal system, a simple pharmacokinetic model to describe plasma 1,3-GDN levels after percutaneous (p.c.) application is presented. As a result, the drug was penetrated through the rat skin in vitro at a zero-order rate, although the penetration rate from the gel base was significantly greater than that from the adhesive. In vivo, the drug was rapidly absorbed through the rat skin, with a peak plasma level of 581 +/- 151 and 265 +/- 62 ng/ml for the gel ointment and adhesive systems without a porous membrane, respectively. The plasma levels after application of the systems with a membrane were relatively constant for a long time, indicating that the membranes act as a controlled-release barrier. The bioavailability of 1,3-GDN after gel base systems with and without a membrane was relatively high. The model presented was successfully able to describe the time course of plasma 1,3-GDN concentrations following p.c. application of the systems.