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Related Experiment Videos

Urate excretion: drug interactions.

G M Fanelli, I M Weiner

    The Journal of Pharmacology and Experimental Therapeutics
    |August 1, 1979
    PubMed
    Summary
    This summary is machine-generated.

    Researchers studied 2-nitroprobenecid in primates. Hippurates reduced its uricosuric effect by inhibiting drug secretion, while pyrazinoate decreased the effect by inhibiting urate secretion, suggesting complex interactions.

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    Area of Science:

    • Pharmacology
    • Nephrology
    • Primate Studies

    Background:

    • Probenecid derivatives are used to study renal transport mechanisms.
    • Understanding drug interactions is crucial for optimizing therapeutic effects and minimizing side effects.

    Purpose of the Study:

    • To investigate the effects of 2-nitroprobenecid on uricosuria in non-human primates.
    • To elucidate the mechanisms by which p-aminohippurate, hippurate, pyrazinoate, and salicylate modify the action of 2-nitroprobenecid.

    Main Methods:

    • Administration of 2-nitroprobenecid to chimpanzees and Cebus monkeys.
    • Infusion of p-aminohippurate (chimpanzee) or hippurate (monkey) to assess effects on uricosuria.
    • Administration of pyrazinoate and salicylate to evaluate their impact on 2-nitroprobenecid's renal disposition and uricosuric response.

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  • Development of a mathematical model to explain observed concentration-response relationships.

    • Main Results:

    • p-Aminohippurate and hippurate diminished the uricosuria induced by 2-nitroprobenecid by inhibiting its secretion.
    • Pyrazinoate reduced the response to 2-nitroprobenecid without altering its renal disposition, by inhibiting urate secretion.
    • Pyrazinoate's effect was diminished at high 2-nitroprobenecid concentrations, suggesting a rightward shift in the concentration-response curve.
    • Salicylate showed a less prominent effect similar to pyrazinoate in chimpanzees.

    Conclusions:

    • The uricosuric effect of 2-nitroprobenecid is modulated by substances affecting its secretion or urate transport.
    • Pyrazinoate's action involves inhibition of urate secretory flux, leading to a competitive-like interaction with 2-nitroprobenecid.
    • A mathematical model supports the hypothesis of large transepithelial urate fluxes influencing drug interactions.