Physiologic pharmacokinetic parameters for FTY720 in rats, dogs, and humans using the whole body PBPK model
Parameters for dogs and humans were derived from those of rats using their respective drug free fractions in blood.
Parameters | Species | ||||||
|---|---|---|---|---|---|---|---|
| Rat | CV% | Dog | Human | ||||
| BW (kg) | 0.362 | 11.65 | 70 | ||||
| f ub | 0.000333 | 0.000241 | 0.000361 | ||||
| CLint (μl/min/mg protein)-microsomes | 88 | N.A. | 33 | ||||
| CLinta (l/h/kg) | 2315 | (12.2) | 1018 | 202 | |||
| F abs | 0.71 | (18.5) | 0.6 | 0.5 | |||
| kabs (h-1) | 0.0007 | (19.3) | 0.00843 | 0.000743 | |||
| R lungs | 41.4 | (12.5) | 29.9 | 44.8 | |||
| R brain | 27.1 | (11.9) | 19.5 | 29.3 | |||
| R heart | 13.8 | (15.0) | 9.96 | 14.9 | |||
| R spleen | 34.7 | (10.5) | 25.0 | 37.5 | |||
| R muscle | 4.69 | (14.1) | 3.39 | 5.08 | |||
| R thymus | 15.8 | (11.72) | 11.4 | 17.1 | |||
| R kidneys | 22.3 | (9.3) | 16.1 | 24.1 | |||
| R LN | 22.9 | (12.9) | 16.5 | 24.8 | |||
| R liver b | 34.9 | (14.6) | 25.2 | 37.8 | |||
| R fat | 0.647 | (9.84) | 0.47 | 0.70 | |||
| R GIT | 11.1 | (54.4) | 8.01 | 12.0 | |||
| R rest-of-body | 50.9 | (8.3) | 36.8 | 55.1 | |||
| PSbrain (ml/min) | 39.3 | (12.1) | 379 | 3613 | |||
| PSthymus (ml/min) | 122 | (11.3) | 572 | 1517 | |||
| PSLN (ml/min) | 176 | (16.9) | 820 | 2173 | |||