Pharmacokinetic studies of the nitroglycerin metabolites, 1,2- and 1,3- glyceryl dinitrates, in the rat.
1,2- and 1,3-glyceryl dinitrates (1,2-GDN and 1,3-GDN) are the primary metabolites of glyceryl trinitrate, a commonly used anti-anginal agent. The goal of this study was to examine the pharmacokinetic properties of these metabolites in rats. Sprague-Dawley rats were infused intravenously with 0.25 or 2.0 micrograms min-1 of either 1,2- or 1,3-GDN for 70 min, during which steady state blood concentrations were achieved. Post-infusion blood samples were collected for 30 min. 1,2-GDN was found to possess slightly higher clearance (32.3 vs 20.8 ml min-1 kg-1) and volume of distribution (695 vs 454 ml kg-1) than 1,3-GDN; however, the two metabolites exhibited similar mean residence times (22.0 vs 21.8 min). Upon an 8-fold increase in the infusion rate, the pharmacokinetic parameters were not significantly altered for either 1,2- or 1,3-GDN. When each GDN was co-infused with an 8-fold higher dose of the other GDN, there were also no significant changes in the parameters.
Lau
D T
DT
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0446.
Gumbleton
M
M
Labisch
C
C
Benet
L Z
LZ
D000818:Animals; D008297:Male; D005996:Nitroglycerin / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains
C014509:dinitroglycerol; D005996:Nitroglycerin