Ketoconazole pharmacokinetics during chronic dosing in adults with haematological malignancy

Autor: Malcolm Richardson, M. T. Bredow, T. K. Daneshmend, R. R. Slade, R. J. Stockley, David W. Warnock
Rok vydání: 1986
Předmět:
Zdroj: European Journal of Clinical Microbiology. 5:513-517
ISSN: 1435-4373
0722-2211
DOI: 10.1007/bf02017693
Popis: 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 less than 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.
Databáze: OpenAIRE
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