Nitroglycerin pharmacokinetics after intravenous infusion in normal subjects

The purpose of this investigation was to examine the pharmacokinetics of nitroglycerin in normal volunteers after intravenous drug administration. Eight subjects (including one subject on two occasions) received a dose of ∼0.6 mg iv of nitroglycerin at a rate of 18 μg/min. Plasma concentrations of intact drug during and after the infusion were determined using a GLC method. Intra- and intersubject variability in nitroglycerin plasma kinetics was substantial. Generally, however, plasma nitroglycerin disposition was characterized by: (a) a large apparent plasma clearance (0.3-1 liter/min/kg), (b) a large volume of distribution (∼3 liters/kg), and (c) a rapid plasma half-life (∼3 min). From the apparent volume of distribution obtained, plasma drug can be estimated to account for only ∼1.3% of total drug in the body. Minor fluctuations in tissue distribution, which can be produced by a myriad of external and internal stimuli, could cause dramatic fluctuation in plasma nitroglycerin concentrations and, hence, in the calculated pharmacokinetic parameters. For example, in two subjects studied, plasma nitroglycerin concentrations oscillated to such an extent that pharmacokinetic analysis could not be performed. In some subjects, steady-state concentrations were not observed in spite of the apparent short plasma half-life, and rebound in plasma concentrations during the postinfusion phase were evident. These phenomena were also observed in other kinetic studies involving organic nitrates.