[Pharmacology of isosorbide dinitrate after transdermal application]

Different organic nitrates exhibit markedly different in vitro partition coefficients, P. The lipophilic character, of which P is a measure, is the most important physico-chemical property which influences the penetration of nitrate molecules through the skin. It follows that there are several possibilities for developing formulations in which the diffusion of the molecules through the layers of the epidermis is furthered. A transdermal spray of isosorbide dinitrate (ISDN, TD Spray Iso Mack) was administered to volunteers and blood concentrations of the nitrate were measured. The results demonstrate that therapeutically effective amounts of the nitrate do in fact penetrate through the various levels of the skin. In addition pharmacokinetic measurements confirm that ISDN penetrates from the sprayed on film into the surface of the skin within 20 min and is then slowly released from the epidermis into the capillaries of the corium. An advantage of the administration of ISDN through the skin lies in the avoidance of the rapid metabolism of the drug which takes place during its first passage through the liver (first-pass effect). The protracted efficacy of the transdermal spray in the treatment of patients with coronary disease is, therefore, due to the unchanged ISDN and not, as with oral treatment, to pharmacologically active metabolites.