Table 3.
T1 Relaxation Times of Protons in Flurbiprofen and Dapsone in CYP2C9 Variants.a
| CYP2C9.1b | CYP2C9.2c | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Compoundd | Proton Resonancee | Flurbiprofen or Dapsone | Flurbiprofen and Dapsone | Flurbiprofen or Dapsone | Flurbiprofen and Dapsone | ||||
| T1 2C9 | T1 2C9+CO | T1 2C9 | T1 2C9+CO | T1 2C9 | T1 2C9+CO | T1 2C9 | T1 2C9+CO | ||
| CH3 | 0.71 (0.00) | 0.73 (0.01) | 0.70 (0.01) | 0.72 (0.01) | 0.67 (0.01) | 0.71 (0.01) | 0.66 (0.01) | 0.69 (0.01) | |
| 2 | 2.67 (0.06) | 3.15 (0.08) | 2.54 (0.06) | 3.06 (0.07) | 2.50 (0.10) | 2.92 (0.18) | 2.56 (0.21) | 2.99 (0.22) | |
| 5 | 2.22 (0.05) | 2.43 (0.05) | 2.18 (0.04) | 2.49 (0.04) | 2.18 (0.12) | 2.71 (0.22) | 1.95 (0.13) | 2.20 (0.23) | |
| Flurbiprofen | 6 | 1.95 (0.03) | 2.20 (0.04) | 1.98 (0.03) | 2.19 (0.03) | 1.96 (0.10) | 2.22 (0.13) | 1.82 (0.13) | 1.90 (0.13) |
| 2′,6′ | 2.46 (0.03) | 2.83 (0.03) | 2.47 (0.02) | 2.85 (0.03) | 2.44 (0.09) | 2.85 (0.01) | 2.45 (0.09) | 2.94 (0.11) | |
| 3′,5′ | 2.49 (0.03) | 2.85 (0.03) | 2.46 (0.03) | 2.86 (0.04) | 2.27 (0.07) | 2.95 (0.12) | 2.37 (0.16) | 2.81 (0.12) | |
| 4′ | 3.87 (0.16) | 4.67 (0.19) | 3.59 (0.07) | 4.86 (0.19) | 3.25 (0.26) | 4.40 (0.31) | 3.51 (0.41) | 4.61 (0.57) | |
| Dapsone | 2,2′,6,6′ | 3.78 (0.02) | 4.83 (0.06) | 3.79 (0.02) | 4.87 (0.03) | 3.89 (0.03) | 3.70 (0.05) | 3.85 (0.03) | 4.58 (0.06) |
| 3,3′,5,5′ | 4.27 (0.04) | 5.31 (0.08) | 4.28 (0.03) | 5.26 (0.05) | 4.34 (0.05) | 5.44 (0.09) | 4.28 (0.06) | 5.31 (0.10) | |
| CYP2C9.3f | CYP2C9.5g | ||||||||
| Flurbiprofen or Dapsone | Flurbiprofen and Dapsone | Flurbiprofen or Dapsone | Flurbiprofen and Dapsone | ||||||
| T1 2C9 | T1 2C9+CO | T1 2C9 | T1 2C9+CO | T1 2C9 | T1 2C9+CO | T1 2C9 | T1 2C9+CO | ||
| CH3 | 0.69 (0.01) | 0.71 (0.01) | 0.69 (0.01) | 0.71 (0.01) | 0.67 (0.01) | 0.70 (0.01) | 0.67 (0.01) | 0.70 (0.01) | |
| 2 | 2.62 (0.07) | 2.96 (0.05) | 2.60 (0.07) | 3.07 (0.09) | 2.55 (0.08) | 2.98 (0.08) | 2.57 (0.08) | 3.06 (0.08) | |
| 5 | 2.18 (0.06) | 2.46 (0.07) | 2.27 (0.05) | 2.44 (0.07) | 1.94 (0.05) | 2.37 (0.08) | 2.05 (0.05) | 2.40 (0.06) | |
| 6 | 1.93 (0.03) | 2.16 (0.05) | 1.95 (0.06) | 2.12 (0.05) | 1.88 (0.04) | 2.03 (0.06) | 1.90 (0.05) | 2.11 (0.05) | |
| 2′,6′ | 2.45 (0.05) | 2.80 (0.04) | 2.52 (0.03) | 2.83 (0.04) | 2.35 (0.03) | 2.82 (0.05) | 2.48 (0.03) | 2.88 (0.04) | |
| 3′,5′ | 2.45 (0.05) | 2.82 (0.06) | 2.45 (0.04) | 2.83 (0.06) | 2.32 (0.05) | 2.82 (0.05) | 2.39 (0.04) | 2.78 (0.04) | |
| 4′ | 3.44 (0.07) | 4.18 (0.14) | 3.61 (0.09) | 4.70 (0.19) | 3.44 (0.10) | 4.46 (0.16) | 3.39 (0.09) | 4.41 (0.19) | |
| 2,2′,6,6′ | 3.87 (0.03) | 4.28 (0.05) | 3.87 (0.03) | 4.67 (0.06) | 3.75 (0.03) | 4.70 (0.03) | 3.82 (0.03) | 4.74 (0.07) | |
| 3,3′,5,5′ | 4.37 (0.04) | 4.92 (0.05) | 4.35 (0.03) | 5.34 (0.07) | 4.23 (0.03) | 5.28 (0.06) | 4.29 (0.04) | 5.31 (0.09) | |
a
Errors for measurements were < 10%.
b
[P450 2C9.1] = 0.016 μM
c
[P450 2C9.2] = 0.005 μM
d
CYP2C9.1 [Flurbiprofen] = 145 μM; [Dapsone] = 100 μM, CYP2C9.2 [Flurbiprofen] = 50 μM; [Dapsone] = 100 μM, CYP2C9.3 [Flurbiprofen] = 140 μM; [Dapsone] = 100 μM, CYP2C9.5 [Flurbiprofen] = 160 μM; [Dapsone] = 100 μM,
e
See Figure 1 for numbering scheme of the protons for flurbiprofen and dapsone. T1 times for the HC-CO2H proton could not be accurately determined due to interference from the residual glycerol resonances.
f
[P450 2C9.3] = 0.014 μM
g
[P450 2C9.5] = 0.016 μM