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Related Experiment Videos

Trimazosin in normotensive subjects.

H L Elliott, J Vincent, D M Hughes

    Clinical Pharmacology and Therapeutics
    |February 1, 1984
    PubMed
    Summary

    Trimazosin, a quinazoline derivative, effectively lowers blood pressure, especially when standing, with effects peaking 4-6 hours post-dose. An active metabolite, 1-hydroxy-trimazosin, may contribute to its hypotensive and alpha 1-antagonist properties.

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    Area of Science:

    • Pharmacology
    • Cardiovascular Medicine

    Background:

    • Trimazosin is a quinazoline derivative investigated for its cardiovascular effects.
    • Understanding its mechanism of action and pharmacokinetic profile is crucial for therapeutic application.

    Purpose of the Study:

    • To evaluate the acute hypotensive effects of oral and intravenous trimazosin in normal subjects.
    • To determine the pharmacokinetic properties of trimazosin.
    • To investigate the role of trimazosin's metabolite in its overall effect.

    Main Methods:

    • Administration of oral and intravenous trimazosin to normal subjects.
    • Measurement of blood pressure and heart rate responses, particularly during postural changes.
    • Pharmacokinetic analysis including bioavailability, clearance, and elimination half-life.
    • Assessment of alpha 1-antagonist properties using phenylephrine infusions.

    Main Results:

    • Trimazosin significantly reduced blood pressure, especially upon standing, with peak effects 4-6 hours post-dose.
    • A significant increase in heart rate accompanied the hypotensive effect.
    • Trimazosin demonstrated selective peripheral alpha 1-antagonist properties.
    • Oral bioavailability was 63%, clearance 66 ml/min, and elimination half-life approximately 3 hours.
    • Inclusion of the metabolite 1-hydroxy-trimazosin improved the correlation between drug levels and hypotensive effect.

    Conclusions:

    • Acute trimazosin administration causes a fall in blood pressure and increase in heart rate.
    • Trimazosin exhibits significant peripheral alpha 1-antagonism.
    • An active metabolite, likely 1-hydroxy-trimazosin, may contribute to the overall hypotensive effect, though its specific receptor antagonist properties require further investigation.

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