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Pharmacokinetic studies of the nitroglycerin metabolites, 1,2‐ and 1,3‐ glyceryl dinitrates, in the rat
Author(s) -
Lau David T.W.,
Gumbleton Mark,
Labisch Christoph,
Benet Leslie Z.
Publication year - 1991
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510120306
Subject(s) - pharmacokinetics , chemistry , volume of distribution , metabolite , pharmacology , metabolism , medicine , biochemistry
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 μgmin −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 21·8 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.