Table 1.
Peak | RFe3+ (sec−1) | RFe2+-CO (sec−1) | RP (sec−1) | rappa (Å) | rmin (Å) |
---|---|---|---|---|---|
260 μM Midazolam
| |||||
1′ | 2.18±0.02 | 1.53±0.04 | 0.65±0.05 | 9.15±0.22 | 7.62±0.18b |
3 | 1.88±0.04 | 1.45±0.18 | 0.43±0.18 | 9.79±0.71 | |
7 | 1.81±0.05 | 1.67±0.09 | 0.14±0.10 | 11.83±1.50 | |
9 | 2.97±0.17 | 1.65±0.12 | 1.31±0.20 | 8.14±0.27 | |
10 | 2.85±0.06 | 1.81±0.11 | 1.03±0.12 | 8.47±0.24 | |
3F | 1.60±0.07 | 1.46±0.20 | 0.14±0.21 | 11.84±2.95 | |
4F | 1.85±0.04 | 1.91±0.07 | −0.06±0.08 | - | 17.02c |
5F | 2.17±0.06 | 1.72±0.10 | 0.45±0.11 | 9.75±0.46 | |
6F | 1.88±0.05 | 1.83±0.11 | 0.05±0.12 | 14.13±6.01 | |
| |||||
260 μM Carbamazepine
| |||||
aa′ | 2.44±0.24 | 1.67±0.11 | 0.77±0.26 | 7.88±0.45 | 7.02±0.40b |
bb′ | 2.56±0.33 | 1.54±0.09 | 1.03±0.34 | 7.51±0.42 | 6.69±0.38b |
cc′ | 2.38±0.23 | 1.59±0.10 | 0.79±0.25 | 7.84±0.41 | 6.98±0.37b |
dd′ | 2.50±0.25 | 1.47±0.09 | 1.03±0.26 | 7.51±0.33 | 6.69±0.29b |
ee′ | 2.22±0.20 | 1.52±0.09 | 0.71±0.22 | 7.99±0.41 | 7.12±0.37b |
rapp was calculated using eq 6.
rmin was calculated based on chemical equivalence (eq 7).
rmin was calculated using the highest RP.
Abbreviations: RFe3+, paramagnetic relaxation rate (sec−1) of oxidized CYP3A4; RFe2+-CO, paramagnetic relaxation rate (sec−1) of reduced CYP3A4 with CO; RP, paramagnetic relaxation rate (i.e. RP=RFe3+−RFe2+-CO). The distances were calculated with a τC of 3 × 10−10 sec, which is the average value of P450s under variety of conditions (31, 49). The NMR relaxation rates of 4a and 4b protons were omitted because of overlap of their NMR peaks with water and aliphatic proton NMR peaks.