Pharmacokinetic studies of the nitroglycerin metabolites, 1,2- and 1,3- glyceryl dinitrates, in the rat

✍ Scribed by David T.-W. Lau; Mark Gumbleton; Christoph Labisch; Leslie Z. Benet

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 393 KB
• Volume: 12
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510120306

✦ Synopsis

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 pgmin-' of either 1,2or 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-' kg-I) and volume of distribution (695 vs 454 ml kg-I) 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 I,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.

KEY worn Pharmacokinetics Glyceryl Nitrate Rat Nitroglycerin