TABLE 1

Kinetic parameters for hydroxylation activities of the wild type and 24 CYP2D6 allelic variants on nebivolol

Data are presented as means ± S.D.

VariantVmaxKmKiIntrinsic Clearance (Vmax/Km)Relative Clearancea
pmol/min per pmol P450μMμMμl/min per pmol P450%
CYP2D6*11.17 ± 0.041.80 ± 0.210.66 ± 0.06100.00
CYP2D6*2 (R297C; S486T)0.77 ± 0.02*1.77 ± 0.452.51 e3 ± 1.06 e30.45 ± 0.10*67.83
CYP2D6*10 (P34S; S486T)0.09 ± 0.01*3.62 ± 1.700.03 ± 0.01*4.07
CYP2D6*87 (A5V)0.56 ± 0.04*5.33 ± 1.45*0.11 ± 0.02*16.83
CYP2D6*88 (V104A)1.38 ± 0.04*2.18 ± 0.16531.30 ± 80.470.63 ± 0.0395.79
CYP2D6*89 (L142S)1.36 ± 0.09*1.86 ± 0.3288.35 ± 34.550.74 ± 0.08111.85
CYP2D6*90 (K147R)0.52 ± 0.04*3.32 ± 1.31278.37 ± 81.940.17 ± 0.05*25.05
CYP2D6*91 (C161S)0.99 ± 0.18*7.97 ± 3.44*0.13 ± 0.03*20.58
CYP2D6*92 (218 frameshift)NDNDNDND
CYP2D6*93 (T249P)0.46 ± 0.04*5.75 ± 0.64*192.83 ± 116.200.08 ± 0.00*12.20
CYP2D6*94 (D337G)0.97 ± 0.00*2.59 ± 0.680.39 ± 0.10*58.23
CYP2D6*95 (R388H)0.48 ± 0.00*2.87 ± 0.550.17 ± 0.03*25.65
CYP2D6*96 (424STOP)NDNDNDND
CYP2D6*97 (F457L)0.77 ± 0.03*1.83 ± 0.170.42 ± 0.02*64.57
CYP2D6*98 (H463D)0.66 ± 0.01*1.49 ± 0.260.45 ± 0.07*67.97
R25Q0.36 ± 0.01*1.04 ± 0.230.35 ± 0.08*52.53
F164L0.66 ± 0.03*1.99 ± 0.473.05e3 ± 4.14 e30.34 ± 0.06*51.17
E215K9.48 e3 ± 2.43 e3*2.31 e5 ± 5.10 e4*0.04 ± 0.00*6.15
F219S1.02 ± 0.03*2.18 ± 0.03656.43 ± 314.340.47 ± 0.01*71.00
V327M0.59 ± 0.01*2.06 ± 0.260.29 ± 0.03*43.77
D336N0.87 ± 0.01*1.61 ± 0.130.54 ± 0.0381.61
V342M1.06 ± 0.021.93 ± 0.170.55 ± 0.0483.16
R344Q0.76 ± 0.03*1.42 ± 0.200.54 ± 0.0583.28
R440C1.85 ± 0.10*1.28 ± 0.1279.04 ± 24.951.44 ± 0.05*219.08
R497C0.46 ± 0.01*1.20 ± 0.090.39 ± 0.02*58.71
  • ND, not determined.

  • a Data are given as a percentage of the wild type.

  • * P < 0.01 (significantly different from wild-type CYP2D6).