TY - JOUR
T1 - Variable Glyceryl Dinitrate Formation Following Infusions of Glyceryl Trinitrate at Different Vascular Sites in the Rat
AU - Nakashima, Emi
AU - Lau, David T.W.
AU - Benet, Leslie Z.
PY - 1991/7
Y1 - 1991/7
N2 - 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.
AB - 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.
KW - clearance
KW - glyceryl
KW - metabolism
KW - nitrate
KW - nitroglycerin
KW - uptake
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U2 - 10.1023/A:1015851412175
DO - 10.1023/A:1015851412175
M3 - Article
C2 - 1924138
AN - SCOPUS:0025726767
VL - 8
SP - 877
EP - 882
JO - Pharmaceutical Research
JF - Pharmaceutical Research
SN - 0724-8741
IS - 7
ER -