Plasma concentrations and haemodynamic effects of nitroglycerin during and after intravenous infusion in healthy volunteers

Abstract

The effects of nitroglycerin, infused intravenously at 3.4 and 7.5 micrograms/min over 30 min, on haemodynamic parameters were determined in the morning and the afternoon in a randomized, placebo-controlled study in 5 healthy volunteers. The mean steady-state concentrations of nitroglycerin reached in the plasma during the infusions of 3.4 and 7.5 micrograms/min were 0.35 +/- 0.06 ng/ml and 0.64 +/- 0.22 ng/ml, respectively. Wide inter-individual variation was noted. The nitroglycerin-induced increase in the orthostatic rise in heart rate and the change in digital-pulse-wave morphology roughly paralleled the plasma concentration, whereas the reduction in systolic blood pressure in the upright position was still evident 15 mins after the infusion, i.e. when nitroglycerin was no longer measurable in plasma. No significant diurnal variation in vascular sensitivity to the vasodilative action of nitroglycerin was demonstrable. The change in pulse-wave morphology resulting from the reduction in peripheral resistance (shift of the dicrotic wave in the descending limb towards the base-line) proved to be the most sensitive haemodynamic parameter.

Nitroglycerin Attenuates Human Endothelial Progenitor Cell Differentiation, Function, and Survival

“…routes generally yields plasma concentrations in the low nanomolar range (Armstrong et al, 1979(Armstrong et al, , 1980Imhof et al, 1982;Curry et al, 1984;Jewell et al, 1992;Hashimoto and Kobayashi, 2003). Nevertheless, we believe that the concentrations used have clinical relevance.…”

“…Nevertheless, we believe that the concentrations used have clinical relevance. Transdermal administration of 4 mg/h GTN yielded a maximal venous plasma concentration of 45 nM in 119 healthy volunteers (Curry et al, 1984), and studies have documented that plasma concentrations exceeding 100 nM can be achieved with moderate intravenous infusion rates of GTN (Imhof et al, 1982;Curry et al, 1993;Booth et al, 1994). Thus, plasma concentrations approaching or exceeding 100 nM are achieved during GTN therapy.…”

Glyceryl‐1‐nitrate pharmacokinetics in healthy volunteers.

“…The analogy is extended by the reduction in the individual variations of pharmacokinetic parameters when pass-sing from the parent substance to the hydrophilic metabolite. Coefficients of variation of plasma parameters observed after infusion of GTN typically are around or above 70% (Armstrong et al, 1982;Armstrong et al, 1983;Idzu et al, 1982;Imhof et al, 1982). For intravenous G-1-N we found the following coefficients of variation: t½and MRT = 14%, Cma, = 22%, V= 25% and CL = 31%.…”

“…These findings support the interpretation that body water is the principal correlate of the volume of G-1-N distribution. For the lipophilic parent substance glyceryl trinitrate (GTN) tissue distribution plays a more important role (Imhof et al, 1982) and the distribution volume is at least twice as high as that of G-1-N (McNiff et al, 1981).…”

Nitroglycerin [BAT Value Documentation, 1998]

“…The data on nitroglycerin concentrations in plasma after intravenous infusion also differ widely (9,19,51,65,84,86,95,102). The reasons for the interindividual and intraindividual variability according to Sorkin et al (95) are the rapid metabolism of nitroglycerin in blood at 37 °C, absorption by PVC, which is used in many intravenous infusion systems, and the differences in the sensitivity of the methods of detection.…”