Effect of CPR on 1:1 CYP2C9/CYP2D6-mediated (S)-flurbiprofen metabolism for various mixing schemes
Addition of excess (20 pmol) CPR significantly (p < 0.05) increased the Vmax ratios in Allmix1 and Allmix2 but not in SeqAdd1 and SeqAdd2. In SeqAdd3, a significant (p < 0.05) increase in Vmax ratios was seen at 2.5 pmol of CYP2D6 only between the two CPR levels. No significant changes were observed in the Km ratios upon addition of excess CPR in all systems. Single-factor analysis of variance was used for statistical comparisons. Data are the mean ± S.D.
CPR | Vmax + 2D6/Vmax-control | Km + 2D6/Km-control | CPR | Vmax + 2D6/Vmax-control | Km + 2D6/Km-control | |
|---|---|---|---|---|---|---|
| pmol/incubation | pmol/incubation | |||||
| SeqAdd1 | 10 | 0.60 ± 0.03 | 0.98 ± 0.23 | 20 | 0.61 ± 0.03 | 0.99 ± 0.12 |
| SeqAdd2 | 10 | 0.69 ± 0.1 | 1.06 ± 0.27 | 20 | 0.78 ± 0.03 | 0.97 ± 0.26 |
| SeqAdd3 | 10 | 0.52 ± 0.1 | 1.32 ± 0.65 | 20 | 0.69 ± 0.1 | 1.07 ± 0.32 |
| Allmix1 | 10 | 0.54 ± 0.01 | 1.43 ± 0.56 | 20 | 0.71 ± 0.05 | 1.05 ± 0.11 |
| Allmix2 | 10 | 0.56 ± 0.04 | 0.78 ± 0.10 | 20 | 0.8 ± 0.05 | 1.01 ± 0.27 |