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Dose dependency of nitroglycerin (GTN) kinetics was examined in 4 dogsafter randomized multiple i.v. infusions of GTN at four different rates: 10, 30,50 and 70 ug/min. Each dose was infused for 210 min into a front leg vein andvenous blood samples were drawn from a femoral vein. Plasma levels of GTN andits dinitrate metabolites, 1,2-GDN and 1,3-GDN, were determined using a GC-ECD method. Steady state concentrations(Css) of GTN, reached at about 60 minin all studies, were not proportional to the infusion rate in 3 of 4 dogs. The ap-parent clearance (determined as infusion rate/Css) decreased as the infusion ratewas inereased, particularly for the 70μg/min infusion, suggesting dose dependentkinetics. Large intra and interdog variability in GTN kinetics was also observed.Dinitrate metabolites of GTN were formed rapidly and reached concentrationsmuch higer than GTN. The Css ratios 1,2-GDN/GTN and 1,3-GDN/GTN(31.5±
Dose dependency of nitroglycerin (GTN) kinetics was examined in 4 dogsafter randomized multiple iv infusions of GTN at four different rates: 10, 30, 50 and 70 ug/min. Each dose was in for for 210 min into a front leg vein andvenous blood samples. Were drawn from a femoral vein. Plasma levels of GTN andits dinitrate metabolites, 1,2-GDN and 1,3-GDN, were determined using a GC-ECD method. Steady state concentrations(Css) of GTN, reached at about 60 minin All studies, were not proportional to the infusion rate in 3 of 4 dogs. The ap-parent clearance (determined as infusion rate/Css) decreased as the infusion ratewas inereased, particularly for the 70μg/min infusion, suggesting dose dependent kinetics. Large intra And interdog variability in GTN kinetics was also observed.Dinitrate metabolites of GTN were formed rapidly and reached concentrationsmuch higer than GTN. The Css ratios 1,2-GDN/GTN and 1,3-GDN/GTN(31.5±)