TABLE 1

Physicochemical and pharmacokinetic parameters of bosutinib in PBPK models

Parameter ValueSource
Molecular weight531Calculated
logP3.1Measured
pKa (monobase)7.9Measured
fu,plasma0.063Measured
B/P1.2Measured
Fa0.5–0.7Estimated from the mass-balance study results
ka (h−1)0.13Estimated from the clinical study results
Lag time (h)1Estimated from the clinical study results
Peff,man (10−4 cm/s)1.8Calculated from physiochemical property
Qgut (l/h)8.7Calculated by Simcyp
fu,gut1Assumed (Simcyp default)
Vss (l/kg)15Predicted from nonclinical results
CLint,CYP3A4 (μl/min per mg protein)300Back-calculated from the observed CL/Foral
CLrenal (l/h)0.9Estimated from the mass-balance study results
kin/kout (h−1)a0.039/0.021Estimated from the two-compartment PK analysis
  • a Distribution rate constants for a single adjustment compartment in minimal-PBPK models used for simulation in HIPs.