Cyclophosphamide metabolism is affected by azole antifungals

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

Research output: Contribution to journalArticle

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
Externally publishedYes

Fingerprint

Azoles
Itraconazole
Metabolism
Cyclophosphamide
Fluconazole
Stem Cell Transplantation
Stem cells
Toxicity
Clinical Trials Data Monitoring Committees
Mycoses
Behavior Therapy
Poisons
Metabolites
Drug-Related Side Effects and Adverse Reactions
Bilirubin
Cytochrome P-450 Enzyme System
Isoenzymes
Creatinine
Safety
Monitoring

ASJC Scopus subject areas

  • Hematology

Cite this

Marr, K., Leisenring, W., Crippa, F., Slattery, J. T., Corey, L., Boeckh, M., & McDonald, G. B. (2004). Cyclophosphamide metabolism is affected by azole antifungals. Blood, 103(4), 1557-1559. https://doi.org/10.1182/blood-2003-07-2512

Cyclophosphamide metabolism is affected by azole antifungals. / Marr, Kieren; Leisenring, Wendy; Crippa, Fulvio; Slattery, John T.; Corey, Lawrence; Boeckh, Michael; McDonald, George B.

In: Blood, Vol. 103, No. 4, 15.02.2004, p. 1557-1559.

Research output: Contribution to journalArticle

Marr, K, Leisenring, W, Crippa, F, Slattery, JT, Corey, L, Boeckh, M & McDonald, GB 2004, 'Cyclophosphamide metabolism is affected by azole antifungals', Blood, vol. 103, no. 4, pp. 1557-1559. https://doi.org/10.1182/blood-2003-07-2512
Marr K, Leisenring W, Crippa F, Slattery JT, Corey L, Boeckh M et al. Cyclophosphamide metabolism is affected by azole antifungals. Blood. 2004 Feb 15;103(4):1557-1559. https://doi.org/10.1182/blood-2003-07-2512
Marr, Kieren ; Leisenring, Wendy ; Crippa, Fulvio ; Slattery, John T. ; Corey, Lawrence ; Boeckh, Michael ; McDonald, George B. / Cyclophosphamide metabolism is affected by azole antifungals. In: Blood. 2004 ; Vol. 103, No. 4. pp. 1557-1559.
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