Pharmacokinetics of nitroglycerin and metabolites in humans following oral dosing

Abstract

Single dose oral nitroglycerin (GTN) was administered to six healthy subjects as 6.5, 9.0, and 13.0 mg aqueous solutions in sequential study phases to characterize the oral pharmacokinetics of GTN and the dinitrate metabolites. Blood samples were collected periodically up to 10 h. Plasma concentrations of GTN were measurable in some subjects up to 1/2 and 1 h, respectively, after the 9.0 and 13.0 mg dose. The mean GTN Cmax values of the three solution doses were 0.28, 0.78, and 0.42 ng ml-1 in ascending dosage. The erratic nature of GTN plasma profiles prevented meaningful pharmacokinetic analysis, although tmax was consistently 5 min. In all three treatments, both GTN metabolites (1,2- and 1,3-glyceryldinitrates, GDNs) peaked at about 20 min, followed by a distributive phase and a log-linear decline in concentrations. Terminal half-lives for both GDNs were approximately 50 min in all three doses. The plasma concentrations of the metabolites were higher than nitroglycerin with 1,2-GDN exhibiting the highest overall profile.