Hanatani Tadaaki, Fukuda Tsuyoshi, Onishi Sachi, Funae Yoshihiko, Azuma Junichi
Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Eur J Clin Pharmacol. 2003 Jul;59(3):233-5. doi: 10.1007/s00228-003-0603-5. Epub 2003 May 17.
CYP2C9 is a polymorphic enzyme, and CYP2C93 is associated with decreased metabolic activity. In addition to the impaired metabolism, we investigated whether the CYP2C93 exhibited altered inhibitory susceptibility compared with CYP2C9*1.
In the present study, CYP2C9.1 and CYP2C9.3 were expressed in yeast. Using typical CYP2C9 substrates (diclofenac, tolbutamide and S-warfarin) and a potent CYP2C9 inhibitor (nicardipine), the Ki values for nicardipine on the three metabolisms in CYP2C91 and CYP2C93 were determined.
The ratios of Ki(CYP2C93)/Ki(CYP2C91) on tolbutamide, diclofenac and S-warfarin metabolisms were 1.2, 3.1 and 0.8, respectively.
In conclusion, there are no significant differences in the inhibitory susceptibility between the two CYP2C9 enzymes.
细胞色素P450 2C9（CYP2C9）是一种多态性酶，CYP2C93与代谢活性降低有关。除代谢受损外，我们还研究了与CYP2C91相比，CYP2C9*3的抑制敏感性是否发生改变。
在本研究中，CYP2C9.1和CYP2C9.3在酵母中表达。使用典型的CYP2C9底物（双氯芬酸、甲苯磺丁脲和S-华法林）和一种强效的CYP2C9抑制剂（尼卡地平），测定尼卡地平对CYP2C91和CYP2C93三种代谢的抑制常数（Ki）值。
甲苯磺丁脲、双氯芬酸和S-华法林代谢中Ki（CYP2C93）/Ki（CYP2C91）的比值分别为1.2、3.1和0.8。
总之，两种CYP2C9酶的抑制敏感性没有显著差异。
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