Pharmacokinetics of nitroglycerin and long-acting nitrate esters

The current literature on the human pharmacokinetics of nitroglycerin, isosorbide dinitrate, and isosorbide mononitrates is briefly reviewed and evaluated. The pharmacokinetics of nitroglycerin are unusual in that its systemic clearance is extremely large and that there is a distinct arterial-venous gradient in plasma concentration. These features had created substantial difficulties in the documentation and interpretation of nitroglycerin plasma concentrations and pharmacokinetics. Studies with isosorbide dinitrate showed that this nitrate is absorbed as intact drug at about 20 percent of a comparable intravenous dose, firmly disproving a previous belief that orally administered nitrate is completely degraded by presystemic metabolism. The current data suggest that plasma nitrate concentration may relate to some of its pharmacologic effects after short-term dosing, but the concentration-response relationship is complex after long-term dosing. Studies of nitrate pharmacokinetics in their presumed sites of action, namely, the vasculature, appear to be useful for the further understanding of the mechanism of action for these vasodilators.