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
Originalien

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.

Key words

Trinitroglycerin Dinitroglycerin β-Blockade 

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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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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