TABLE 1

PF-06282999 Simcyp model input parameters

Input Parameter
Mol. wt (g/mol)325.77Fa1.0
cLog P0.49ka (h−1)0.3
pKa (monoprotic base)7.82Vdss (l/kg)0.45
Blood/plasma (Rbp)0.94
fu,plasma0.376CLpo (l/h)14
fu,gutEqual to fu,plasmaCLrenal (l/h)7.8
Qgut (l/h)5.0
CYP3A4, kdeg, CYP3A4 (h−1)0.0289
  • cLog P, calculated partition coefficient (Dong et al., 2016); CLpo, oral clearance (Dong et al., 2016); CLrenal, renal clearance (Dong et al., 2016); Fa, fraction absorbed; fu,gut, unbound fraction in gut; fu,plasma, unbound fraction in plasma (Dong et al., 2016); ka, absorption rate constant (Dong et al., 2016); kdeg,CYP3A4, degradation rate constant for CYP3A4; Qgut, gut blood flow; pKa, acid dissociation constant (Dong et al., 2016);Rbp, blood-to-plasma ratio (Dong et al., 2016); Vdss, steady-state volume of distribution (Dong et al., 2016).