A significant role of human cytochrome P450 2C8 in amiodarone N-deethylation : an approach to predict the contribution with relative activity factor
作者： Tsuyoshi Yokoi , Sumika Nakamura , Katsuhiro Ohyama , Miki Nakajima , Hiroshi Yamazaki
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摘要: Human cytochrome P450 (CYP) isoforms involved in amiodarone N-deethylation were identified, and the relative contributions of these CYP evaluated different human liver microsomes. The mean K(M) V(max) values microsomes from six livers 31.6 +/- 7.5 microM 1.2 0.7 pmol/min/pmol CYP, respectively. Ketoconazole anti-CYP3A antibodies strongly inhibited N-deethylase activity at a substrate concentration 50 microM. Of 15 recombinant enzymes (19 preparations), CYP1A1, CYP3A4, CYP1A2, CYP2D6, CYP2C8, CYP2C19 catalyzed N-deethylation. 5 was significantly correlated with paclitaxel 6alpha-hydroxylase (r = 0.84, P <.05) microsomes, whereas 100 testosterone 6beta-hydroxylase 0.94, <.005). According to concept factor, it clarified that CYP2C8 as well CYP3A4 clinically significant concentrations CYP2C19, CYP2D6 relatively minor. However, there large interindividual variability contribution each isoform liver; relevance would be dependent on content respective liver.
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