Table 1.
Michaelis-Menten Kinetic Parameters for Demethylation Activities of Wild-Type CYP2C9*1 and 37 Mutant CYP2C9 Alleles Toward Sildenafil
| Variants | Vmax (pmol/min/pmol) | Km (µM) | CLint (µL/min/µmol) | Relative Clearance (% of Wild Type) |
|---|---|---|---|---|
| CYP2C9*1 | 0.75±0.02 | 42.75±2.45 | 17.46±0.45 | 100.00 |
| CYP2C9*2 | 0.88±0.05 | 64.75±6.99 | 13.71±0.79 | 78.10 |
| CYP2C9*3 | 0.30±0.01** | 89.98±3.22** | 3.30±0.07** | 18.89 |
| CYP2C9*8 | 0.35±0.00* | 153.73±0.06** | 2.25±0.01** | 12.87 |
| CYP2C9*11 | 1.13±0.01** | 60.71±0.60 | 18.55±0.23 | 106.20 |
| CYP2C9*13 | 0.11±0.01 | 155.23±12.01* | 0.74±0.02** | 4.21 |
| CYP2C9*14 | 0.96±0.13 | 57.48±22.69 | 17.72±3.96 | 100.72 |
| CYP2C9*16 | 0.47±0.00* | 45.96±8.98 | 10.58±0.12 | 60.64 |
| CYP2C9*19 | 0.19±0.06* | 280.63±114.29 | 0.70±0.08** | 3.96 |
| CYP2C9*23 | 0.54±0.01* | 42.57±1.45 | 12.60±0.13* | 72.09 |
| CYP2C9*27 | 0.92±0.02* | 59.77±1.89* | 15.44±0.29 | 88.42 |
| CYP2C9*29 | 0.96±0.20 | 85.60±48.25 | 12.49±3.53 | 71.05 |
| CYP2C9*31 | 0.76±0.03 | 39.48±3.94 | 19.30±1.18 | 110.66 |
| CYP2C9*34 | 0.39±0.03** | 111.70±8.74* | 3.51±0.16** | 20.05 |
| CYP2C9*36 | 0.07±0.00** | 224.97±12.59* | 0.32±0.00** | 1.82 |
| CYP2C9*37 | 0.51±0.09 | 73.53±33.54 | 7.69±2.54 | 41.00 |
| CYP2C9*38 | 0.31±0.03** | 20.47±5.50 | 15.59±3.01 | 87.04 |
| CYP2C9*39 | 0.28±0.03** | 46.46±14.72 | 6.24±1.44* | 34.91 |
| CYP2C9*40 | 1.17±0.12 | 140.93±26.79 | 8.36±0.69** | 47.83 |
| CYP2C9*41 | 1.13±0.12 | 178.47±52.69 | 6.63±1.40* | 37.11 |
| CYP2C9*42 | 0.07±0.00** | 83.50±31.53 | 0.89±0.25*** | 5.00 |
| CYP2C9*43 | 0.46±0.23 | 1,044.00±540.35 | 0.45±0.03** | 2.38 |
| CYP2C9*44 | 0.82±0.16 | 142.40±68.39 | 6.37±1.93 | 34.98 |
| CYP2C9*45 | 0.18±0.02*** | 54.15±13.77 | 3.39±0.54*** | 19.17 |
| CYP2C9*46 | 0.29±0.02** | 66.54±11.44 | 4.48±0.51*** | 25.62 |
| CYP2C9*47 | 0.25±0.04** | 52.47±15.16 | 4.91±0.69** | 27.95 |
| CYP2C9*48 | 0.70±0.06 | 193.07±33.91 | 3.68±0.29*** | 20.97 |
| CYP2C9*49 | 1.11±0.01** | 63.31±2.64 | 17.51±0.53 | 100.15 |
| CYP2C9*50 | 0.28±0.00** | 70.54±3.24* | 3.94±0.11** | 22.56 |
| CYP2C9*51 | 0.20±0.00** | 51.84±2.83 | 3.89±0.15** | 22.27 |
| CYP2C9*52 | 0.19±0.01** | 62.53±6.19 | 3.00±0.16** | 17.13 |
| CYP2C9*53 | 0.29±0.02** | 47.46±1.69 | 6.09±0.18** | 34.84 |
| CYP2C9*54 | 0.22±0.01** | 60.71±5.28 | 3.61±0.22** | 20.69 |
| CYP2C9*55 | 0.26±0.00** | 49.92±3.98 | 5.18±0.32*** | 29.64 |
| CYP2C9*56 | 0.37±0.02** | 76.22±7.41 | 4.83±0.20** | 27.64 |
| CYP2C9*58 | 0.41±0.02** | 129.13±12.93 | 3.18±0.15** | 18.24 |
| CYP2C9*59 | 0.10±0.00** | 231.80±33.88 | 0.45±0.04** | 2.54 |
| CYP2C9*60 | 0.25±0.04* | 156.97±58.23 | 1.64±0.27*** | 9.20 |
Notes: *Significantly different from wild-type CYP2C9, *p < 0.05, **p < 0.01, ***p < 0.001.
Abbreviation: N.D., not determined.