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 Ki values for nicardipine on the three metabolisms in CYP2C9*1 and CYP2C9*3 were determined. RESULT: The ratios of Ki(CYP2C9*3)/Ki(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.
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 Ki values for nicardipine on the three metabolisms in CYP2C9*1 and CYP2C9*3 were determined. RESULT: The ratios of Ki(CYP2C9*3)/Ki(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.
Authors: T S Klose; G C Ibeanu; B I Ghanayem; L G Pedersen; L Li; S D Hall; J A Goldstein Journal: Arch Biochem Biophys Date: 1998-09-15 Impact factor: 4.013
Authors: I Ieiri; H Tainaka; T Morita; A Hadama; K Mamiya; M Hayashibara; H Ninomiya; S Ohmori; M Kitada; N Tashiro; S Higuchi; K Otsubo Journal: Ther Drug Monit Date: 2000-06 Impact factor: 3.681
Authors: Russell A Wilke; Richard L Berg; Humberto J Vidaillet; Michael D Caldwell; James K Burmester; Michael A Hillman Journal: Clin Med Res Date: 2005-11