Parameters used to calculate Cmax,u(portal) and R values for MKIs with Cmax,u/IC50 > 0.1
Data were obtained from the following references: Frohna et al., 2006; Hazarika et al., 2008; Hughes et al., 2009; van Erp et al., 2009; Yamamoto et al., 2009; Tanaka et al., 2010; Larson et al., 2012; McTigue et al., 2012; O’Brien and Fallah Moghaddam, 2013.
| MKI | Dose | Fa | fu | Cmax,u(portal) | R[ka 0.03]a | R[ka 0.1] | R[ka 0.03] | R[ka 0.1] | |
|---|---|---|---|---|---|---|---|---|---|
| ka 0.03 | ka 0.1 | eq. 3 | eq. 3 | eq. 4 | eq. 4 | ||||
| mg | µM | ||||||||
| OATP1A2 | |||||||||
| Cediranib | 30 | 1 | 0.03 | 0.037 | 0.130 | 2.23 | 5.43 | 2.12 | 4.94 |
| Erlotinib | 150 | 0.60 | 0.07 | 0.620 | 1.32 | 1.56 | 2.20 | ||
| OATP1B3 | |||||||||
| Erlotinib | 1.52 | 2.11 | |||||||
| OATP2B1 | |||||||||
| Erlotinib | 21.7 | 45.0 | 16.1 | 33.2 | |||||
| Gefitinib | 250 | 0.59 | 0.09 | 0.818 | 2.52 | 2.26 | 4.88 | ||
| OAT3 | |||||||||
| Nilotinib | 300 | 0.31 | 0.02 | 0.117 | 0.270 | 1.29 | 1.66 | ||
Fa, reported oral bioavailability of the MKI.
↵a rB = 1, except for gefitinib (0.76; Li et al., 2006).