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Related Experiment Videos

Cyclosporin-erythromycin interaction in normal subjects.

D J Freeman, R Martell, S G Carruthers

    British Journal of Clinical Pharmacology
    |June 1, 1987
    PubMed
    Summary

    Erythromycin significantly increases cyclosporin (CYA) levels in the body, raising the risk of toxicity. Careful monitoring or alternative antibiotics are recommended for patients taking both drugs.

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    Area of Science:

    • Pharmacology
    • Drug Interactions
    • Clinical Pharmacy

    Background:

    • Cyclosporin (CYA) is an immunosuppressant drug with a narrow therapeutic index.
    • Erythromycin is a common antibiotic that can affect drug metabolism.

    Purpose of the Study:

    • To investigate the pharmacokinetic interaction between cyclosporin and erythromycin in healthy subjects.
    • To determine the impact of erythromycin on cyclosporin absorption, metabolism, and clearance.

    Main Methods:

    • Plasma CYA concentrations were measured using high-performance liquid chromatography (h.p.l.c.) and radioimmunoassay (RIA).
    • Estimates of metabolite formation were derived from inter-assay differences.
    • Pharmacokinetic parameters including Cmax, AUC, Tmax, and oral clearance were analyzed.

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    Main Results:

    • Erythromycin significantly increased maximum plasma CYA concentration (Cmax) and area under the concentration-time curve (AUC).
    • Time to maximum concentration (Tmax) and apparent oral clearance of CYA were significantly decreased.
    • A reduction in apparent metabolite proportion was observed at peak CYA concentrations.

    Conclusions:

    • The drug interaction between erythromycin and CYA primarily involves decreased hepatic first-pass metabolism, though impaired absorption cannot be ruled out.
    • Concomitant administration of CYA and erythromycin increases the risk of CYA toxicity in patients.
    • Therapeutic drug monitoring and dose adjustments or alternative antibiotic selection are crucial for managing this interaction.