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Nitroglycerin disposition in human blood.

P A Cossum, M S Roberts

    European Journal of Clinical Pharmacology
    |January 1, 1985
    PubMed
    Summary
    This summary is machine-generated.

    Nitroglycerin (GTN) is quickly metabolized in red blood cells to dinitro-metabolites and mononitronitrates. This nitroglycerin metabolism in blood is concentration-dependent and can be halted with iodoacetamide.

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    Area of Science:

    • Pharmacokinetics and Drug Metabolism
    • Biochemistry

    Background:

    • Nitroglycerin (GTN) is a vasodilator used to treat angina.
    • Understanding GTN disposition in blood is crucial for optimizing its therapeutic use.

    Purpose of the Study:

    • To investigate the in vitro disposition and metabolism of nitroglycerin (GTN) and its metabolites in erythrocytes, plasma, and whole blood.

    Main Methods:

    • Utilized radiolabeled (3H) and unlabeled GTN and its metabolites.
    • Employed High-Performance Liquid Chromatography (HPLC) for separation and analysis.
    • Studied GTN metabolism in erythrocyte suspensions, plasma, and blood samples.

    Main Results:

    • GTN rapidly metabolized in erythrocytes (t1/2 3 min) to dinitro-metabolites and then mononitronitrates.

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  • Metabolism was concentration-dependent, with observed plasma protein binding of 11-60% for GTN and dinitro-metabolites.
  • Erythrocyte-plasma partition coefficient ranged from 0.6 to 0.9.
  • Dinitro-metabolites partially inhibited GTN metabolism by erythrocytes.
  • Metabolism in patient blood samples was inhibited by adding iodoacetamide to chilled tubes.

    • Conclusions:

    • Erythrocytes play a significant role in nitroglycerin metabolism.
    • The disposition of GTN and its metabolites is complex, involving concentration-dependent metabolism and protein binding.
    • Iodoacetamide effectively inhibits GTN metabolism in collected blood samples, facilitating further pharmacokinetic studies.