Ketoconazole pharmacokinetics during chronic dosing in adults with haematological malignancy

R. J. Stockley, T. K. Daneshmend, M. T. Bredow, D. W. Warnock, M. D. Richardson, R. R. Slade

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Ketoconazole pharmacokinetics were determined in nine adults with haematological malignancy after one week on a 200 mg daily dose and later after one week on a 400 mg daily dose. The area under the serum concentration time curve (AUC) reached 12.3 ± 7.7 mg/l.h (mean ± S.D.) on the 200 mg dose and increased to 23.0 ± 18.2 mg/l.h on the 400 mg dose (p <0.05). The half-life of ketoconazole was 3.1 + 1.9 h on the 200 mg dose and 3.5 ± 1.7 h on the 400 mg dose. Peak concentrations were 3.2 ±1.8 mg/l and 4.6 ± 3.2 mg/l on the 200 mg and 400 mg doses, respectively. Trough ketoconazole concentrations were undetectable 24 h after either dose. There was no correlation between the leucocyte count and any pharmacokinetic parameter for ketoconazole. Variation in AUC was 20-fold on the 200 mg daily dose and 8-fold on the 400 mg per day regimen. Measurement of serum levels during ketoconazole treatment appears necessary in view of the unpredictable concentrations achieved. Once-a-day dosage regimens of ketoconazole in immunocompromised patients may be inappropriate. Future clinical trials should adopt a two or three times a day dosing regimen, as this may confer a pharmacokinetic and therapeutic advantage. © 1986 Friedr. Vieweg & Sohn Verlagsgesellschaft mbH.
    Original languageEnglish
    Pages (from-to)513-517
    Number of pages4
    JournalEuropean Journal of Clinical Microbiology
    Volume5
    Issue number5
    DOIs
    Publication statusPublished - Oct 1986

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