Pharmacokinetic-hemodynamic studies of nitroglycerin ointment in congestive heart failure

Abstract

The aim of this study was to determine the bioavailability of nitroglycerin after application of nitroglycerin ointment in patients with heart failure and to examine whether a correlation exists between plasma nitroglycerin and its hemodynamic effects. The dose of nitroglycerin ointment selected was based on the prior hemodynamic response of individual patients to an intravenous infusion of nitroglycerin. Nine patients received 1 to 2 inches of nitroglycerin ointment on a single skin site (small dose group) and five patients received 4 inches (2 inches to two separate skin sites, large dose group). There was good correlation between the dose of nitroglycerin ointment and bioavailability (area under the plasma concentration time curve from 0 to 240 minutes) (r = 0.81, p < 0.001). We observed a decrease in both pulmonary capillary wedge pressure and right atrial pressure 30 minutes after application of nitroglycerin ointment. The maximal changes in pulmonary capillary wedge pressure were from 28 ± 7 to 23 ± 8 mm Hg and in right atrial pressure from 14 ±7 to 11 ±6 mm Hg. There was a greater decrease in pulmonary capillary wedge pressure in the small dose group (31 percent) compared with the large dose group (13 percent) (p < 0.001). Plasma nitroglycerin concentration in the small dose group increased to 3.1 ± 3.0 ng/ ml at 60 minutes and remained at that level through 240 minutes. In the large dose group a plasma nitroglycerin level of 8.9 ± 4.0 ng/ ml was achieved at 60 minutes and sustained through 240 minutes. Despite this plasma nitroglycerin level there was little decline in pulmonary capillary wedge pressure. This study demonstrates a good relation between the dose of nitroglycerin ointment and nitroglycerin bioavailability; nitroglycerin ointment also provides therapeutic levels of nitroglycerin associated with substantial hemodynamic benefit in selected patients with cardiac failure.