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5-fluorocytosine and amphotericin B in bronchial secretions

J E Pennington, E R Block, H Y Reynolds

    Antimicrobial Agents and Chemotherapy
    |September 1, 1974
    PubMed

    Insights

    5-fluorocytosine achieved effective bronchial concentrations against Candida species for 3 hours in dogs. Amphotericin B showed poor penetration into bronchial secretions, limiting its efficacy for respiratory fungal infections.

    Area of Science:

    • Pharmacology
    • Mycology
    • Respiratory Medicine

    Background:

    • Antifungal drug penetration into bronchial secretions is crucial for treating pulmonary fungal infections.
    • Understanding drug pharmacokinetics in the respiratory tract is essential for optimizing treatment strategies.

    Purpose of the Study:

    • To compare the penetration and clearance of 5-fluorocytosine and amphotericin B into bronchial secretions.
    • To evaluate the in vivo efficacy of these antifungals against Candida species in a canine model.

    Main Methods:

    • A dog model was used to assess drug concentrations in bronchial secretions after intravenous administration.
    • Minimal inhibitory concentrations (MICs) for Candida species were determined.
    • Pharmacokinetic parameters of 5-fluorocytosine and amphotericin B in bronchial secretions were analyzed.

    Main Results:

    • Intrabronchial concentrations of 5-fluorocytosine exceeded MICs for 80-90% of Candida species for up to 3 hours post-dose.
    • Amphotericin B demonstrated poor penetration across the blood-bronchus barrier at tested intravenous doses (0.6 and 1.2 mg/kg).

    Conclusions:

    • 5-fluorocytosine exhibits favorable penetration into bronchial secretions, suggesting potential for treating respiratory candidiasis.
    • Amphotericin B's limited bronchial penetration may restrict its use in certain pulmonary fungal infections, warranting further investigation into optimized delivery methods.

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