Vascular Pharmacokinetics of Nitrates

  • H.-L. Fung
  • S. C. Sutton
  • A. Kamiya
Conference paper
Part of the International Boehringer Mannheim Symposia book series (BOEHRINGER)

Abstract

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 [2] and changes in pulmonary capillary pressure in patients with recent myocardial infarction [4]. A similar, albeit less quantitative, picture has been seen with isosorbide dinitrate (ISDN). Thus, Thadani et al. [5] demonstrated that some parallelism in exercise tolerance and plasma concentration existed after acute ISDN doses of 15–120 mg. Fung et al. [6] 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.

Keywords

Glycerin Glutathione Nitrite NADPH Cardiol 

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References

  1. 1.
    Fung H-L (1983) Pharmacokinetics of nitroglycerin and long acting nitrate esters. Am J Med 74 [Suppl 6 B]: 13–20PubMedCrossRefGoogle Scholar
  2. 2.
    Fung H-L (1984) Pharmacokinetic determinants of nitrate action. Am J Med 76 [Suppl 6 A]: 22–26PubMedCrossRefGoogle Scholar
  3. 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
  4. 4.
    Reifart N, Bussmann W-D, Schirmer M, Kaltenbach M (1981) Haemodynamic efficacy, duration of action and pharmacokinetics of 80 mg isosorbide-5-mononitrate in recent myocardial infarction. Med Welt 32: 540PubMedGoogle Scholar
  5. 5.
    Thadani U, Fung H-L, Darke AC, Parker JO (1980) Oral isosorbide dinitrate in the treatment of angina pectoris. Dose response relationship and duration of action during acute therapy. Circulation 62: 491–502PubMedGoogle Scholar
  6. 6.
    Fung H-L, McNiff EF, Ruggirello D, Darke A, Thadani U, Parker JO (1981) Kinetics of isosorbide dinitrate and relationships to pharmacological effects. Br J Clin Pharmacol 11: 579–590PubMedGoogle Scholar
  7. 7.
    Thadani U, Fung H-L, Darke AC, Parker JO (1982) Oral isosorbide dinitrate in angina pectoris. Comparison of duration of action and dose response relationship during acute and sustained therapy. Am J Cardiol 49: 411–419PubMedCrossRefGoogle Scholar
  8. 8.
    Parker JO, Vankoughnett KA, Fung H-L (1984) Transdermal isosorbide dinitrate in angina pectoris. Effect of acute and sustained therapy. Am J Cardiol 54: 8–13PubMedCrossRefGoogle Scholar
  9. 9.
    Fung H-L, Sutton SC, Kamiya A (1984) Blood vessel uptake and metabolism of organic nitrates in the rat. J Pharmacol Exp Ther 228: 334–341PubMedGoogle Scholar
  10. 10.
    Sutton SC, Fung H-L (1983) Effect of dosage regimen on the development of tolerance to nitroglycerin in rats. J Cardiovasc Pharmacol 5: 1086–1092PubMedCrossRefGoogle Scholar
  11. 11.
    Needleman P, Johnson EM Jr (1973) Mechanisms of tolerance development to organic nitrates. J Pharmacol Exp Ther 184: 709–715PubMedGoogle Scholar
  12. 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

Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • H.-L. Fung
  • S. C. Sutton
  • A. Kamiya

There are no affiliations available

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