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 µg/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 ≥ LFV > LFA ≥ HPV. Furthermore, the GDN formation ratios (1,2-GDN/1,3-GDN) are different: LFV ≥ LJV > LFA > 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.
|ジャーナル||Pharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists|
|出版ステータス||Published - 1991 7月|
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