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Chlorothiazide absorption from solution and tablet dosage forms in dogs

W F Ebling, A F Murro, F J Voelker

    Journal of Pharmaceutical Sciences
    |February 1, 1981
    PubMed
    Summary
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    This study compared chlorothiazide bioavailability in dogs using an aqueous solution versus three different tablets. Results showed no significant bioavailability differences between the solution and some tablets, despite variations.

    Area of Science:

    • Pharmacology
    • Drug Bioavailability Studies

    Background:

    • Chlorothiazide is a diuretic medication used to treat edema and hypertension.
    • Assessing the bioavailability of different chlorothiazide formulations is crucial for ensuring therapeutic efficacy.

    Purpose of the Study:

    • To evaluate and compare the bioavailability of an aqueous chlorothiazide solution against three commercially available chlorothiazide tablets in adult mongrel dogs.

    Main Methods:

    • Two crossover urinary excretion studies were conducted using six fasting adult mongrel dogs.
    • Dogs received single 500-mg doses of chlorothiazide in various formulations: aqueous solution, originator tablets (500mg and 250mg), and a generic tablet.
    • Urinary excretion of chlorothiazide was measured to determine bioavailability, with analysis for a hydrolysis product.

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    Main Results:

    • Urinary recoveries of chlorothiazide were low across all formulations, ranging from 15.7% to 22.0% of the administered dose.
    • No statistically significant differences in bioavailability were found between the aqueous solution and specific tablets (A-2, B).
    • Significant interindividual and some intraindividual variations in chlorothiazide bioavailability were observed.

    Conclusions:

    • The tested chlorothiazide tablets demonstrate comparable bioavailability to the aqueous solution in dogs.
    • The observed variations highlight the importance of considering individual patient responses to chlorothiazide therapy.
    • Further research may be warranted to explore factors contributing to the low and variable urinary recoveries.