Abstract
Objective
CYP2C9 is a polymorphic enzyme, and CYP2C9*3 is associated with decreased metabolic activity. In addition to the impaired metabolism, we investigated whether the CYP2C9*3 exhibited altered inhibitory susceptibility compared with CYP2C9*1.
Method
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 K i values for nicardipine on the three metabolisms in CYP2C9*1 and CYP2C9*3 were determined.
Result
The ratios of K i (CYP2C9*3) /K i (CYP2C9*1) on tolbutamide, diclofenac and S-warfarin metabolisms were 1.2, 3.1 and 0.8, respectively.
Conclusion
In conclusion, there are no significant differences in the inhibitory susceptibility between the two CYP2C9 enzymes.
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Acknowledgements
This work was supported a grant (no. 99–2) from the Organization for Pharmaceutical Safety and Research. A part of this study was supported by a Grant-in-Aid for Scientific Research (nos. 12204072, 12470525 and 13204052) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Hanatani, T., Fukuda, T., Onishi, S. et al. No major difference in inhibitory susceptibility between CYP2C9.1 and CYP2C9.3. Eur J Clin Pharmacol 59, 233–235 (2003). https://doi.org/10.1007/s00228-003-0603-5
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DOI: https://doi.org/10.1007/s00228-003-0603-5