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

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Summary

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.

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Abbreviations

AUC:

Area under curve

DNG:

1,2 Dinitroglycerin

h:

hour

min:

Minute

ml:

Milliliter

ng:

Nanogram

ns:

not significant

TNG:

Nitroglycerin

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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.

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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). https://doi.org/10.1007/BF01740593

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Key words

  • Trinitroglycerin
  • Dinitroglycerin
  • β-Blockade