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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1557-1559.
Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-07-2512.
 Previous Article | Table of Contents | Next Article 
TRANSPLANTATION
Brief report
Cyclophosphamide metabolism is affected by azole antifungals
Kieren A. Marr,
Wendy Leisenring,
Fulvio Crippa,
John T. Slattery,
Lawrence Corey,
Michael Boeckh, and
George B. McDonald
From the Fred Hutchinson Cancer Research Center and University of Washington, Seattle, WA.
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.
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