Drug metabolism by flavin-containing monooxygenases of human and mouse

• Published in: Expert opinion on drug metabolism & toxicology Vol. 13; no. 2; p. 167
• Main Authors: Phillips, Ian R, Shephard, Elizabeth A
• Format: Journal Article
• Language: English
• Published: England 01.02.2017
• Subjects: Animals; Cytochrome P-450 Enzyme System - metabolism; Genetic Variation; Humans; Mice; Models, Animal; Oxygenases - genetics; Oxygenases - metabolism; Pharmaceutical Preparations - metabolism; Species Specificity; Animal model; mouse; drug metabolism; flavin-containing monooxygenase; FMO; CYP; cytochrome P450; genetic variant; human; knockout mouse
• ISSN: 1744-7607
• DOI: 10.1080/17425255.2017.1239718

Flavin-containing monooxygenases (FMOs) play an important role in drug metabolism. Areas covered: We focus on the role of FMOs in the metabolism of drugs in human and mouse. We describe FMO genes and proteins of human and mouse; the catalytic mechanism of FMOs and their significance for drug metabolism; differences between FMOs and CYPs; factors contributing to potential underestimation of the contribution of FMOs to drug metabolism; the developmental and tissue-specific expression of FMO genes and differences between human and mouse; and factors that induce or inhibit FMOs. We discuss the contribution of FMOs of human and mouse to the metabolism of drugs and how genetic variation of FMOs affects drug metabolism. Finally, we discuss the utility of animal models for FMO-mediated drug metabolism in humans. Expert opinion: The contribution of FMOs to drug metabolism may be underestimated. As FMOs are not readily induced or inhibited and their reactions are generally detoxifications, the design of drugs that are metabolized predominantly by FMOs offers clinical advantages. Fmo1 ,Fmo2 ,Fmo4 mice provide a good animal model for FMO-mediated drug metabolism in humans. Identification of roles for FMO1 and FMO5 in endogenous metabolism has implications for drug therapy and initiates an exciting area of research.