Nitroglycerin disposition in human blood

Abstract

The disposition in vitro of nitroglycerin (GTN) and its metabolites in erythrocyte suspensions, plasma and blood has been studied using labelled (³H) and unlabelled GTN and GTN metabolites separated by HPLC. GTN was rapidly metabolised (t_1/2 3 min) to dinitro-metabolites and subsequently to the mononitronitrates in erythrocyte suspensions containing a therapeutic concentration of GTN (0.8–10 ng/ml). The metabolism of GTN and its dinitro-metabolites was concentration dependent. GTN and its dinitro-metabolites were plasma protein bound (11–60%). They had an apparent erythrocyte-plasma partition coefficient in the range 0.6 to 0.9. The metabolism of GTN by erythrocytes was partially inhibited by the presence of the dinitro-metabolites of GTN. The metabolism of GTN in blood samples collected from patients could be stopped by adding the collected blood to chilled tubes containing the enzyme inhibitor iodoacetamide.