Multiple dose pharmacokinetics of an oral solution of itraconazole in patients receiving chemotherapy for acute myeloid leukaemia

Archibald G. Prentice, David W. Warnock*, Stephen A.N. Johnson, Peter C. Taylor, Debra Oliver

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)

Abstract

The multiple dose pharmacokinetics of a solution of itraconazole given orally were measured in an open study of 20 patients undergoing remission induction chemotherapy for acute myeloid leukaemia. Patients were given itraconazole 5 mg/kg od, 2.5 mg/kg bd, 2.5 mg/kg odor 1.25 mg/kg bd. The mean daily dose of itraconazole was 407 mg for patients receiving 5 mg/kg/day and 148 mg in patients receiving 2.5 mg/kg/day. Mean concentrations of 493 and 495 μ/L were achieved on day 8 in patients who received 5 mg/kg/d od or 2.5 mg/kg bd itraconazole respectively. However, mean concentrations were significantly lower for those who received 2.5 mg/kg od itraconazole being 110 μg/L on day 8. Mean areas under the serum-concentration time curves were also markedly higher in patients receiving 5 mg/kg/day than in those receiving 2.5 mg/kg/day itraconazole and were 22,382 and 5615 μg.h/L on day 15 respectively. These findings suggest that the serum concentrations attained with an oral solution of 5 mg/kg itraconazole either once daily or in two divided doses are suitable for antifungal prophylaxis in patients receiving chemotherapy for acute myeloid leukaemia.

Original languageEnglish
Pages (from-to)657-663
Number of pages7
JournalJournal of Antimicrobial Chemotherapy
Volume36
Issue number4
DOIs
Publication statusPublished - Oct 1995

Bibliographical note

Funding Information:
We thank our fellow investigators Drs Robin Aitchison, Adrian Copplestone, Adrian Newland and Malcolm Phillips and nurses Jane Antil, Joy Chadwick, Sue Lunness, Maria Ormesher and Barbara Spencer for their cooperation and Geoff Webb and Elizabeth Healing for their assistance during the study and in preparing the manuscript. The trial was supported by the Janssen Research Foundation.

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