CLint, uptakea (µl/min/106 cells) | Predicted CLbloodb (ml/min/kg) | Predicted CLhepaticc (ml/min/kg) | In vivo CLbloodd (ml/min/kg) | In vivo CLhepaticc (ml/min/kg) | Fold Error CLhepatic (Observed/ Predicted) | |
---|---|---|---|---|---|---|
Rat, fexofenadine | ||||||
Control | 1.92 ± 0.8 | 1.7 ± 0.7 | 1.1 ± 0.5 | 10.9 ± 3.4 | 7.2 ± 2.7 | 6.5 |
Elacridar, 1 µM | 4.6 ± 1.6** | 3.8 ± 1.3* | 2.5 ± 0.9* | 2.9 | ||
Elacridar, 2 µM | 7.6 ± 1.1** | 6.0 ± 0.8** | 4.1 ± 0.6** | 1.8 | ||
Human, erythomycin | ||||||
Control | 4.4 ± 0.3 | 1.9 ± 0.3 | 1.9 ± 0.3 | 8.8 ± 2.2 | 8.5 ± 2.2 | 4.5 |
Elacridar, 0.5 µM | 5.7 ± 0.8** | 2.4 ± 0.4** | 2.4 ± 0.4** | 3.6 |
Mean ± SD, n = 3; ***P < 0.001, **P < 0.01, *P < 0.05, significantly different from control experiments without elacridar.
↵a CLint, uptake was measured using suspended hepatocytes.
↵b CLblood was predicted from CLint, uptake using the well-stirred model, as described (Sohlenius-Sternbeck et al., 2012).
↵c CLhepatic was calculated from CLblood using data from Swift et al. (2009).
↵d In vivo CLblood was measured in house in Sprague-Dawley rats (Lundquist P et al., 2014). Human pharmacokinetic parameters are from Sun et al. (2010).