TABLE 6.
The changes in tissue transfer rate and clearance values with the total concentration model
| Route of Administration | Intravenous | Oral | |||||
|---|---|---|---|---|---|---|---|
| Genotype | Wild Type | Mdr1a/b−/−Bcrp1−/− | Wild Type | Bcrp1−/− | Mdr1a/b−/− | Mdr1a/b−/−Bcrp1−/− | |
| Kin (h−1) | Mean | 1.12E−04 | 1.12E−04 | 1.18E−04 | 1.18E−04 | 1.18E−04 | 1.18E−04 |
| CV (%) | — | 16.5 | — | — | — | 18.5 | |
| Kout (h−1) | Mean | 12.3 | 0.432 | 16.8 | 11.3 | 0.282 | 0.300 |
| CV (%) | 7.14 | 19.0 | 14.1 | 10.9 | 8.25 | 18.5 | |
| CLin (ml/h per kilogram) | Mean | 0.131 | 0.131 | 0.138 | 0.138 | 0.138 | 0.138 |
| CV (%) | — | 16.5 | — | — | — | 17.5 | |
| CLout (ml/h per kilogram) | Mean | 5.1 | 0.181 | 7.1 | 4.73 | 0.118 | 0.126 |
| CV (%) | 7.14 | 19.0 | 14.1 | 10.9 | 8.25 | 18.5 | |
| MTT (h) | 0.082 | 2.315 | 0.060 | 0.089 | 3.55 | 3.33 | |
| CLin/Clout | 0.026 | 0.72 | 0.019 | 0.029 | 1.17 | 1.10 | |
CLin, total drug clearance into the brain; CLout, total drug clearance out of the brain; Kin, tissue transfer rate constant into the brain; Kout, tissue transfer rate constant out of the brain; MTT, mean transit time in the brain: calculated by 1/Kout.