In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin.
Article Details
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Colburn DE, Giles FJ, Oladovich D, Smith JA
In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin.
Hematology. 2004 Jun;9(3):217-21. doi: 10.1080/10245330410001701585.
- PubMed ID
- 15204103 [ View in PubMed]
- Abstract
PURPOSE: Antifungal prophylaxis is an important component of induction therapy for patients with acute myeloid leukemia (AML). Azole antifungal agents are increasingly used in this context. In vitro assays were performed to assess whether cytochrome P450 (CYP450) enzymes were affected by combinations of cytarabine or idarubicin with itraconazole or caspofungin. METHODS: The high throughput microtiter assay was used to determine whether cytarabine, idarubicin and itraconazole or caspofungin were CYP450 isoenzyme substrates, inhibitors of CYP450 isoenzymes, and to determine potential CYP450 metabolism interactions between these agents. RESULTS: Idarubicin is a substrate for CYP450 2D6 and 2C9. Cytarabine is a substrate of CYP450 3A4. Idarubicin inhibits CYP450 2D6, and cytarabine, itraconazole, and caspofungin inhibit CYP450 3A4. Cytarabine metabolism was significantly decreased when combined with caspofungin or itraconazole. CONCLUSIONS: The inhibition of cytarabine metabolism may have important clinical implications. These in vitro findings warrant investigation with in vivo pharmacokinetic studies.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Caspofungin Cytochrome P450 3A4 Protein Humans UnknownInhibitorDetails Cytarabine Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails Idarubicin Cytochrome P450 2C9 Protein Humans UnknownSubstrateDetails Idarubicin Cytochrome P450 2D6 Protein Humans UnknownSubstrateDetails