Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

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

  • 17 Accesses

  • 7 Citations


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.

This is a preview of subscription content, log in to check access.



Area under curve


1,2 Dinitroglycerin










not significant




  1. 1.

    Davidov ME, Mroczek WJ (1977) Effect of sustained released nitroglycerin capsules on anginal frequency and exercise capacity: a double-blind evaluation. Angiology 28:181–189

  2. 2.

    Wendkos MH, Meshulam N (1973) Comparative effects of placebo and sustained-release nitroglycerin in anginal subjects. J Clin Pharmacol 13:160–166

  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 2:19–25

  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 6:68–71

  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 239:277–286

  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 17:301–306

  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 303:373–377

  8. 8.

    Greenblatt DJ, Divoll M, Harmatz JS, Shader RI (1980) Oxazepam kinetics: effects of age and sex. J Pharmacol Exp Ther 215:86–91

  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 27:416–419

  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 109:1187–1191

  11. 11.

    Bogaert MG, Rosseel MT, De Schaepdryver AF (1968) Cardiovascular effects of glyceryldinitrates as compared to glyceryltrinitrate. Arch Int Pharmacodyn 176:458–460

  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 49:270–276

  13. 13.

    Leitold M, Laufen H, Fleissig W (1983) Isosorbiddinitrat und Glycerintrinitrat. Krankenhausarzt 56:112–122

  14. 14.

    Di Carlo FJ (1975) Nitroglycerin revisited: chemistry, biochemistry, interactions. Drug Metab Rev 4:1–38

  15. 15.

    Fung H-L (1984) Pharmacokinetic determinants of nitrate action. Amer J Med 76 (Suppl 6A):22–26

  16. 16.

    Greenblatt DJ, Franke K, Huffman DJ (1978) Impairment of antipyrine clearance in humans by propranolol. Circulation 57:1161–1164

  17. 17.

    Ochs HR, Greenblatt DJ, Verburg-Ochs B (1984) Propranolol interactions with diazepam, lorazepam, and alprazolam. Clin Pharmacol Ther 36:451–455

Download references

Author information

Additional information

Dedicated to Prof. Dr. H.J. Dengler's 60th year

Supported in part by Grant OC 10/6-4 from Deutsche Forschungsgemeinschaft and by Grant MH-34223 from the United States Public Health Service.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ochs, H.R., Verburg-Ochs, B. & Greenblatt, D.J. Kinetics of 1,2-dinitroglycerin following sustained release nitroglycerin: Influence of propranolol and metoprolol. Klin Wochenschr 63, 1170–1173 (1985).

Download citation

Key words

  • Trinitroglycerin
  • Dinitroglycerin
  • β-Blockade