Cyclophosphamide metabolism is affected by azole antifungals

Kieren A. Marr, Wendy Leisenring, Fulvio Crippa, John T. Slattery, Lawrence Corey, Michael Boeckh, George B. McDonald

Research output: Contribution to journalArticlepeer-review

Abstract

We performed a randomized trial to compare the safety and efficacy of itraconazole with fluconazole in preventing fungal infections in patients undergoing allogeneic stem cell transplantation (SCT). Itraconazole (intravenous 200 mg daily, or oral solution 2.5 mg/kg 3 times daily) and fluconazole (intravenous or oral, 400 mg daily) were administered with the start of conditioning therapy, until at least 120 days after SCT. After enrollment of the first 197 patients, a data and safety monitoring board reviewed potential drug-related toxicities. Patients who received itraconazole developed higher serum bilirubin and creatinine values in the first 20 days after SCT, with highest values in patients who received itraconazole concurrent with cyclophosphamide (CY) conditioning. Analysis of CY metabolism in a subset of patients demonstrated higher exposure to toxic metabolites among recipients of itraconazole compared with fluconazole. These data suggest that azole antifungals, through differential inhibition of hepatic cytochrome P-450 isoenzymes, affect CY metabolism and conditioning-related toxicities.

Original languageEnglish (US)
Pages (from-to)1557-1559
Number of pages3
JournalBlood
Volume103
Issue number4
DOIs
StatePublished - Feb 15 2004

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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