[The pharmacology and pharmacokinetics of glycerol-2-nitrate]

Glyceryl 2-nitrate (G-2-N), which is the major metabolite of glyceryl trinitrate (GTN, Nitro Mack, glyceryl 1-nitrate (G-1-N) and isosorbide-5-nitrate (IS-5-N, Mono Mack) were examined in a comparative study. The haemodynamic and antianginal properties and the spasmolytic activity on blood vessels were investigated in the rat and dog. Also examined were the pharmacokinetics of G-2-N in the rat and of oral GTN in the dog. Strips of rat aorta contracted with potassium chloride or with norepinephrine were relaxed by G-2-N, but somewhat more weakly than with IS-5-N or G-1-N. After oral administration to the anaesthetized rat or to the conscious dog G-2-N exhibited antianginal and hypotensive activity for 6 h. The duration of action of orally administered GTN in the dog depended on the concentration used and was between 15 and 360 min. The half-life of elimination of G-2-N in the rat came to 2 h, and the substance was 100% bioavailable. The concentrations of G-2-N found in the walls of rat vena cava caudalis and rat aorta abdominalis were twice as high as those in blood or plasma. After oral administration of GTN to the conscious dog, G-2-N is the main metabolite, followed by G-1-N, glyceryl 1,2-dinitrate (1,2-GDN), and glyceryl 1,3-dinitrate (1,3-GDN). After a large oral dose of GTN (30 mg/kg), G-2-N contributes to the pharmacodynamic effect from the 3rd h or earlier.