Single oral dose pharmacokinetics of erythromycin and roxithromycin and the effects of chronic dosing

D. J. Birkett, R. A. Robson, N. Grgurinovich, A. Tonkin

    Research output: Contribution to journalArticle

    29 Citations (Scopus)

    Abstract

    Roxithromycin is a semisynthetic macrolide antibiotic having similar in vitro antibacterial profile and potency to erythromycin but possibly greater in vivo potency. The single and multiple oral dose pharmacokinetics of roxithromycin and erythromycin were studied in 12 healthy volunteers. Plasma concentrations of the two compounds were measured by a sensitive and specific high-performance liquid chromatographic method using electrochemical detection. After single doses, roxithromycin 150 mg gave a Cmax 3.3-fold higher and an area under the curve (AUC) 16.2-fold higher than erythromycin 250 mg. The half-life for roxithromycin was 12.42 ± 3.94 h compared with 1.53 ± 0.42 h for erythromycin. On multiple dosing, the AUC over a dosing interval for erythromycin (250 mg, six hourly doses) was increased 2.3-fold compared with the single dose, whereas that for roxithromycin (150 mg, 12 hourly) was decreased by 25.4%. Because of these opposing changes during chronic dosing, the average plasma roxithromycin concentration over the dosing interval was 2.6-fold higher than that for erythromycin, which was a smaller excess than would have been predicted from the single dose data. The results suggest that roxithromycin exerts less inducing and inhibiting effects on human cytochrome P450 than erythromycin. Roxithromycin has a favorable pharmacokinetic profile suitable for twice daily dosing and may have a lower potential than erythromycin for cytochrome P450-mediated drug interactions.

    Original languageEnglish
    Pages (from-to)65-71
    Number of pages7
    JournalTHERAPEUTIC DRUG MONITORING
    Volume12
    DOIs
    Publication statusPublished - Jan 1990

    Keywords

    • Erythromycin
    • Human
    • Multiple-dose effects
    • Pharmacokinetics
    • Roxithromycin
    • Single dose

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