Influence of the method of application on pharmacokinetics of nitroglycerin from ointment in humans

A study was designed to test the influence of surface area on the percutaneous absorption of nitroglycerin from a commercial ointment formulation, using a simple crossover design. On separate occasions, three volunteers were given 16 mg of nitroglycerin (2%) over a 25- and 100-cm2 area. Plasma nitroglycerin concentration was measured at 30, 45, 60, and 90 min using a sensitive capillary GLC-electron-capture detection method capable of quantitating to 150 pg/ml. Plasma concentrations at all times increased at least twofold with the increased surface area; highest observed concentrations were 0.17 and 0.41 ng/ml, respectively. A fourth volunteer received 16 and 32 mg of nitroglycerin over 100 cm2. Doubling the dose increased the 0-90-min AUC by only 76% but caused a 3.5-fold increase in the 90-min plasma concentration. These results suggest that the surface area of application significantly influences the pharmacokinetics of nitroglycerin ointment.