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Variable glyceryl dinitrate formation following infusions of glyceryl trinitrate at different vascular sites in the
E Nakashima1, D T Lau, L Z Benet
1Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0446.
Abstract:
The availability of glyceryl trinitrate (GTN) and the differential formation of dinitrate metabolites (GDNs) in various organs as a function of routes of administration were investigated in the rat. GTN was infused at 2.0 micrograms/min via the left femoral vein (LFV), left external jugular vein (LJV), left femoral artery (LFA), and hepatic portal vein (HPV). Blood concentrations of GTN and GDNs were measured in femoral arterial samples. Different infusions yielded GTN steady-state concentrations in the following rank order: LJV greater than or equal to LFV greater than LFA greater than or equal to HPV. Furthermore, the GDN formation ratios (1,2-GDN/1,3-GDN) are different: LFV greater than LJV greater than LFA greater than HPV. The availabilities of GTN through the leg, vein, and liver were derived. GTN is significantly extracted and metabolized in these organs, and the leg and the vein prefer 1,2-GDN formation, while the liver forms 1,3-GDN predominantly.