Vascular Pharmacokinetics of Nitrates
The relevance of plasma nitrate concentration in describing and understanding the therapeutic action of organic nitrate vasodilators has been recently reviewed [1, 2]. It has been shown that after acute administration, changes in some of the pharmacologic and/or therapeutic effects parallel those of plasma drug concentration. In the case of isosorbide-5-mononitrate (IS-5-MN), e.g., plasma drug concentration correlated well with the decrease in systolic blood pressure in dogs  and changes in pulmonary capillary pressure in patients with recent myocardial infarction . A similar, albeit less quantitative, picture has been seen with isosorbide dinitrate (ISDN). Thus, Thadani et al.  demonstrated that some parallelism in exercise tolerance and plasma concentration existed after acute ISDN doses of 15–120 mg. Fung et al.  also showed that patients who were hypersensitive to a single dose of 60 mg ISDN exhibited half the systemic clearance value of ISDN (i.e., twice the mean plasma concentration over the dosing period) compared with the nonhyper-sensitive group.
KeywordsGlycerin Glutathione Nitrite NADPH Cardiol
Unable to display preview. Download preview PDF.
- 3.Sponer G, Kuhnle HF, Strein K, Bartsch W, Endele R, Dietmann K (1983) Pharmacokinetic aspects of isosorbide-5-mononitrate in dogs. J Pharmacol Exp Ther 228: 235–239Google Scholar
- 12.Ignarro LJ, Lippton H, Edwards JC, Bancos WH, Hyman AL, Kadowitz PJ, Grueter CA (1981) Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside, and nitric oxide: evidence for the involvement of S-nitrosothiol as active intermediates. J Pharmacol Exp Ther 218: 739–749PubMedGoogle Scholar