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Cytochrome P450

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Handbook of Anticancer Pharmacokinetics and Pharmacodynamics

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

Cytochrome P450 (CYP, CYP450, or P450) represents the enzyme that metabolizes drugs with various manners of oxidation as the Phase I reaction. A variety of anticancer drugs are metabolized by P450, including tegafur, cyclophosphamide, ifosfamide, vinca alkaloids, tamoxifen, etoposide, docetaxel, paclitaxel, and molecular-targeting drugs. The variation in drug metabolism causes pharmacokinetic variability and may influence drug efficacy and toxicity. Drug metabolism depends on both genetic and environmental factors, which include genetic polymorphism and drug interactions (induction or inhibition of P450 activity). CYP3A4 is the major human P450 isoform with a remarkable interindividual variation in its activity. With regard to CYP3A4 and CYP3A5, environmental factors appear to influence the CYP3A enzymatic activity more than genetic status. The challenges have been made to control the phenotypic CYP3A4 activity and to reduce pharmacokinetic variability of the relevant drugs. However, the clinical advantages obtained from these efforts should be carefully evaluated in view of clinical practice.

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  1. Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan

    Yuichi Ando M.D., Ph.D.

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  1. Yuichi Ando M.D., Ph.D.
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Correspondence to Yuichi Ando M.D., Ph.D. .

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  1. Sidney Kimmel Comprehensive Cancer Cente, Baltimore, Maryland, USA

    Michelle A. Rudek

  2. Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA

    Cindy H. Chau

  3. Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA

    William D. Figg

  4. Moffitt Cancer Center, Tampa, Florida, USA

    Howard L. McLeod

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Ando, Y. (2014). Cytochrome P450. In: Rudek, M., Chau, C., Figg, W., McLeod, H. (eds) Handbook of Anticancer Pharmacokinetics and Pharmacodynamics. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9135-4_16

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