Estimation of hepatic clearance of E2074 by using the dispersion model
| Species | fp | Rb | fmic | CLint,u | CLh,vitro | CLb |
|---|---|---|---|---|---|---|
| ml/min/mg protein | l/h/kg | l/h/kg | ||||
| Rat | 0.675 | 0.89 | 1 | 0.196 | 3.19 | 3.60 ± 0.14 |
| Dog | 0.601 | 0.86 | 1 | 0.208 | 1.83 | 1.97 ± 0.30 |
| Monkey | 0.676 | 1.01 | 1 | 0.084 | 2.00 | 1.34 ± 0.14 |
CL, clearance; CLb, CL/Rb; CLh,vitro, hepatic blood clearance; CLint,u, intrinsic clearance; E2074, 2-[(2R)-2-fluoro-3-{(3r)-[(3-fluorobenzyl)oxy]-8-azabicyclo[3.2.1]oct-8-yl}propyl]-4,5-dimethyl-2,4-dihydro-3H-1,2,4-triazol-3-one; fmic, unbound fraction in liver microsomes; fp, unbound fraction in plasma; Rb, blood to plasma partition ratio.