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Related Experiment Videos

Polymorphic acetylation of hydralazine

J A Timbrell, S J Harland, V Facchini

    Clinical Pharmacology and Therapeutics
    |September 1, 1980
    PubMed
    Summary
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    Hydralazine acetylation in hypertensive patients shows genetic differences in drug metabolism. The study reveals that the drug hydralazine is polymorphically acetylated, impacting its metabolite excretion based on acetylator phenotype.

    Area of Science:

    • Pharmacogenetics
    • Clinical Pharmacology
    • Drug Metabolism

    Background:

    • Hydralazine is a widely used antihypertensive medication.
    • Individual variability in drug response suggests genetic influences on metabolism.
    • Understanding hydralazine acetylation is crucial for optimizing therapy.

    Purpose of the Study:

    • To investigate the acetylation of hydralazine in hypertensive patients.
    • To determine the relationship between acetylator phenotype and hydralazine metabolite excretion.
    • To analyze the metabolic profile of hydralazine and its acetylated metabolites.

    Main Methods:

    • Acetylator phenotyping using sulfamethazine.
    • Quantification of hydralazine and metabolites (MTP, HOMTP) in urine via gas-liquid and high-pressure liquid chromatography.

    Related Experiment Videos

  • Analysis of 0- to 24-hour urine samples.

    • Main Results:

    • Excretion of hydralazine and 3-hydroxymethyltriazolophthalazine (HOMTP) correlated with acetylator phenotype.
    • Methyltriazolophthalazine (MTP) excretion was not phenotype-related.
    • A bimodal distribution in the HOMTP:hydralazine metabolic ratio was observed, with significantly lower ratios in slow acetylators compared to rapid acetylators.

    Conclusions:

    • Hydralazine undergoes polymorphic acetylation in humans.
    • The acetylator phenotype significantly influences hydralazine metabolism and excretion.
    • HOMTP is an acetylated metabolite, but not the primary one previously identified.