Inhibitor and Conc. Range | Hepatocytes | HLM | |||||||
---|---|---|---|---|---|---|---|---|---|
Donor 1 | Donor 2 | ||||||||
KIa | KI, u | kinacta | KI | KI, u | kinact | KIb | KI, u | kinact | |
μM | min−1 | μM | min−1 | μM | min−1 | ||||
CLA, 12.8–80 μM | 7.88 (3.09) | 7.64 | 0.040 (0.005) | 17.20 (2.80) | 16.86 | 0.028 (0.002) | 15.72 (3.52) | 5.09 | 0.063 (0.008) |
DIL, 0.25–16 μM | 3.55 (1.33) | 3.12 | 0.027 (0.004) | 3.80 (0.59) | 3.38 | 0.014 (0.001) | 0.67 (0.2) | 0.55 | 0.019 (0.014) |
ERY, 0.5–500 μM | 21.40 (4.60) | 20.03 | 0.016 (0.002) | 116.0 (6.10) | 108.58 | 0.055 (0.001) | 1.70 (0.49) | 1.48 | 0.017 (0.002) |
VER, 0.31–20 μM | 2.99 (0.35) | 2.80 | 0.032 (0.001) | 2.58 (0.57) | 2.41 | 0.020 (0.001) | 3.50 (1.47) | 2.05 | 0.053 (0.007) |
TAO, 0.05–1.6 μM | 0.56 (0.084) | 0.40 | 0.050 (0.004) | 1.05 (0.11) | 0.75 | 0.038 (0.002) | 0.19 (0.04) | 0.03 | 0.065 (0.004) |
↵a KI and kinact of each inhibitor in hepatocytes and HLM (S.D. in parentheses) were obtained from nonlinear regression analyses of observed kobs values shown in Figure 2.
↵b KI, u values were calculated by KI multiplied by fu shown in Table 2. In addition to the KI values measured in the study, they were also reported in literature: CLA = 5.49 μM, 0.072 min−1 (Mayhew et al., 2000); DIL = 3.3 μM, 0.07 min−1 (Yeo and Yeo, 2001); ERY = 10.9 μM, 0.046 min−1 (McConn et al., 2004); VER = 2.9 μM, 0.15 min−1 (Yeo and Yeo, 2001); VER = 4.2 μM, 0.092 min−1 (Polasek et al., 2004); and TAO = 0.26 μM, 0.12 min−1 (Atkinson et al., 2005).