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Pharmacokinetics of nitroglycerin and metabolites in humans following oral dosing
Author(s) -
K. Yu Dale,
Giesing Dennis H.,
Williams Roger L.,
Benet Leslie Z.,
Lin Emil T.
Publication year - 1988
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/bod.2510090606
Subject(s) - pharmacokinetics , cmax , pharmacology , chemistry , metabolite , dosing , oral administration , plasma concentration , bioavailability , active metabolite , medicine , biochemistry
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 C max 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 t max 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.