Parameter | Value | Reference |
---|---|---|
Physicochemical | ||
Molecular Weight (g/mol) | 255.36 | Stattera NDA |
Log P | 3.9 | NDA |
pKa | 9.8 | NDA |
fu | 0.025 | NDA |
B/P | 0.623 | Simcyp prediction toolbox |
Absorption | ||
Fa | 0.96 | |
ka (l/h) | 1.2 | Optimized |
Qgut (l/h) | 11.9 | Simcyp prediction toolbox |
Distribution | ||
Vss (l/kg) | 0.74 | Simcyp prediction full PBPK method 2 |
Metabolism/elimination | ||
CLi.v. (l/h) | 16.3 | NDA |
CLr (l/h) | 0.185 | Sauer et al. (2003) |
fm,CYP2D6 | 0.876 | |
Recombinant CLint (μl/min/pmol) | ||
CYP2D6 | 25.4 | |
CYP2C19 | 1.84 | |
P450 enzyme abundance (pmol/mg microsomal protein) | ||
CYP2D6 EM | 8 (61)a | Simcyp default value |
CYP2C19 EM | 14 (40)a | Optimized |
Interaction | ||
CYP2D6 Ki (μM) | 34.3 | Sauer et al. (2004) |
CYP3A4 Ki (μM) | 3.6 | Sauer et al. (2004) |
B/P, blood-to-plasma ratio; CLi.v., clearance after intravenous administration; CLr, renal clearance; Fa, fraction absorbed; fm, fraction metabolized; fu, fraction unbound in plasma; ka, absorption rate constant; Ki, inhibition constant; Log P, log octanol:water partition coefficient; Qgut, drug absorption flow to intestine; Vss, volume of distribution at steady state.
↵a Mean value (coefficient of variance).