Klinische Wochenschrift

, Volume 63, Issue 22, pp 1170–1173 | Cite as

Kinetics of 1,2-dinitroglycerin following sustained release nitroglycerin: Influence of propranolol and metoprolol

  • H. R. Ochs
  • B. Verburg-Ochs
  • D. J. Greenblatt


Ten healthy volunteers ingested a single 18-mg oral dose of sustained release nitroglycerin (TNG) (Giulini-Pharma) on three occasions: once in the control state, once during coadministration of propranolol (80-mg three times daily), and once during coadministration of metoprolol (100-mg twice daily). The degree of beta adrenergic blockade was evaluated by the metaproterenol infusion test. Plasma concentration of TNG and its major metabolite, 1,2-dinitroglycerin (DNG), during 12 h after each dose were measured by gas chromatography-mass spectrometry. Intact TNG was not detected in the plasma of any patient. The major metabolite, DNG, was easily measurable in blood, and had a biphasic plasma concentration profile. Coadministration of the beta-blockers had no influence on any of the kinetic variables for DNG. The mean values during control, propranolol, and metoprolol trials of DNG elimination half-life were: 1.35, 1.10, and 1.09 h; total area under the curve: 42, 38, and 42 ng/ml × h; oral clearance: 6.6, 7.2, and 6.4 liters/min. Thus TNG when administered as a sustained release oral preparation is rapidly and completely transformed to DNG. There was no pharmacokinetic interaction between sustained release TNG and two commonly used beta-blocking agents, suggesting that any clinical interaction that may-occur between sustained release nitroglycerin and beta-blocking agents is pharmacodynamic rather than pharmacokinetic in nature.

Key words

Trinitroglycerin Dinitroglycerin β-Blockade 



Area under curve


1,2 Dinitroglycerin










not significant




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  1. 1.
    Davidov ME, Mroczek WJ (1977) Effect of sustained released nitroglycerin capsules on anginal frequency and exercise capacity: a double-blind evaluation. Angiology 28:181–189Google Scholar
  2. 2.
    Wendkos MH, Meshulam N (1973) Comparative effects of placebo and sustained-release nitroglycerin in anginal subjects. J Clin Pharmacol 13:160–166Google Scholar
  3. 3.
    Amsterdam EA, Awan NA, DeMaria AN, Miller RR, Williams DO, Mason DT (1979) Sustained salutary effects of oral controlled-release nitroglycerin on ventricular function in congestive heart failure. Clin Cardiol 2:19–25Google Scholar
  4. 4.
    Settlage JA, Gielsdorf W, Jaeger H (1983) Femtogram level quantitative determination of nitroglycerin and metabolites in human plasma by GC-MS negative ion chemical ionization, single ion monitoring. Journal of High Resolution Chromatography & Chromatography Communications 6:68–71Google Scholar
  5. 5.
    Miyazaki H, Ishibashi M, Hashimoto Y, Idzy G, Furuta Y (1982) Simultaneous determination of glyceryl trinitrate and its principal metabolites, 1,2- and 1,3-glyceryl dinitrate, in plasma by gas chromatography-negative ion chemical ionization-selected ion monitoring. J Chromatogr 239:277–286Google Scholar
  6. 6.
    Ochs HR, Greenblatt DJ, Woo E, Franke K, Smith TW (1978) Effect of propranolol on pharmacokinetics and acute electrocardiographic changes following intravenous quinidine in humans. Pharmacology 17:301–306Google Scholar
  7. 7.
    Ochs HR, Carstens G, Greenblatt DJ (1980) Reduction in lidocaine clearance during continuous infusion and by coadministration of propranolol. N Engl J Med 303:373–377Google Scholar
  8. 8.
    Greenblatt DJ, Divoll M, Harmatz JS, Shader RI (1980) Oxazepam kinetics: effects of age and sex. J Pharmacol Exp Ther 215:86–91Google Scholar
  9. 9.
    Neurath GB, Dunger M (1977) Blood levels of the metabolites of glyceryl trinitrate and pentaerythritol tetranitrate after administration of a two-step preparation. Arzneim Forsch 27:416–419Google Scholar
  10. 10.
    Schneider W, Kaltenbach M, Stahl B, Bussmann W-D (1984) Anti-anginal efficacy of oral nitroglycerin. A clinical double-blind study with dose-effect relationship. Dtsch Med Wochenschr 109:1187–1191Google Scholar
  11. 11.
    Bogaert MG, Rosseel MT, De Schaepdryver AF (1968) Cardiovascular effects of glyceryldinitrates as compared to glyceryltrinitrate. Arch Int Pharmacodyn 176:458–460Google Scholar
  12. 12.
    Axelsson KL, Andersson RGG, Wikberg JES (1981) Correlation between vascular smooth muscle relaxation and increase in cyclic GMP induced by some organic nitro esters. Acta Pharmacol et Toxicol 49:270–276Google Scholar
  13. 13.
    Leitold M, Laufen H, Fleissig W (1983) Isosorbiddinitrat und Glycerintrinitrat. Krankenhausarzt 56:112–122Google Scholar
  14. 14.
    Di Carlo FJ (1975) Nitroglycerin revisited: chemistry, biochemistry, interactions. Drug Metab Rev 4:1–38Google Scholar
  15. 15.
    Fung H-L (1984) Pharmacokinetic determinants of nitrate action. Amer J Med 76 (Suppl 6A):22–26Google Scholar
  16. 16.
    Greenblatt DJ, Franke K, Huffman DJ (1978) Impairment of antipyrine clearance in humans by propranolol. Circulation 57:1161–1164Google Scholar
  17. 17.
    Ochs HR, Greenblatt DJ, Verburg-Ochs B (1984) Propranolol interactions with diazepam, lorazepam, and alprazolam. Clin Pharmacol Ther 36:451–455Google Scholar

Copyright information

© Springer-Verlag GmbH & Co. KG 1985

Authors and Affiliations

  • H. R. Ochs
    • 1
    • 4
  • B. Verburg-Ochs
    • 2
  • D. J. Greenblatt
    • 3
  1. 1.Medizinische UniversitätsklinikBonn-VenusbergGermany
  2. 2.Institut für Anästhesiologie der Universität BonnGermany
  3. 3.Division of Clinical PharmacologyTufts-New England Medical CenterBoston
  4. 4.MarienkrankenhausSoest

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