Physicochemical and pharmacokinetic parameters of crizotinib used for PBPK model

Parameters (Units)Parameters (Units)
Molecular weight450CLint (μl/min per milligram protein)c
pKa5.4 and 8.9CLint,others26–44
fu,plasma0.093CLrenal (l/h)2.25
Rbp1.1Time-dependent inhibition on CYP3A
Fa0.3–0.5KI (μM)0.89
ka (h−1)a0.01–0.3kinact (h−1)0.78
Qgut (l/h)4.0CYP3A4 induction
fu,gutb0.085Emax (fold)2.4
Vss (l/kg)25EC50 (μM)0.84
  • Rbp, blood-to-plasma ratio.

  • a The value of ka was adjusted to simulate the clinically observed tmax of approximately 4 hours.

  • b The value of fu,gut was assumed as fu,blood calculated by fu,plasma and Rbp.

  • c The values of CLint in human liver microsomes were back-calculated from the clinically observed CL estimates using a retrograde model implemented in Simcyp.