Calculated model parameters and predictions of the 3D regimen as perpetrators of intestinal or systemic efflux transporters and hepatic uptake transporters
| Drug | Intestinal/Hepatic/Renal | Hepatic | |||||
|---|---|---|---|---|---|---|---|
| P-gp | BCRP | OATP1B1 | OATP1B3 | OCT1 | |||
| [I2]/IC50 | [I1]/IC50 | [I2]/IC50 | [I1]/IC50 | R-Value | |||
| Paritaprevir | 20.6 | 0.05 | 1328 | 3.25 | 2.6 | 3.9 | – |
| Ritonavir | 1585 | 6.34 | 23.1 | 0.09 | 1.05 | 1.05 | 1.01 |
| Ombitasvir | – | – | – | – | – | – | – |
| Dasabuvir | 121 | 0.12 | 130 | 0.13 | 1.02 | 1.00 | – |
| M1 | – | 0.02 | – | 0.02 | 1.03 | 1.01 | – |
[I] 1 represents the mean steady-state total (free and bound) Cmax after administration of the highest proposed clinical dose as described in eq. 3. [I]2 is oral dose of inhibitor/250 ml as described in eq. 4. Dashes indicate that parameters were not calculated because the IC50 could not be estimated due to no or low inhibition at the highest tested concentration in vitro. The R-value is the ratio of unbound inhibitor concentration at the inlet to the liver to in vitro IC50, as described in eq. 5.