TABLE 4

GastroPlus ACAT model input parameters for panobinostat

Parameter (unit)Value
Dosage formImmediate release tableta
logPb2.8
Solubility (mg/ml)0.064 at pH 7.6
PKa8.4
Dose volume (ml)250
Particle density (g/ml)b1.2
Mean particle radius (µm) (S.D.b)15 (0)
Particle radius bin1
Precipitation time (s)b900
Diffusion coefficient (cm2/s × 105)b0.43
Permeability (cm/s × 104)2.289
Simulation time (h)48
Body weight (kg)69.1 (20) 67.8 (30) 79.1 (40 mg)
First-pass elimination in small intestine (%)60
First-pass elimination in liver, %26.1
CL (liters/h/kg)c0.433
Vc (liters/kg)c0.325
k12 (per h)c1.81
k21 (per h)c0.507
k13 (per h)c1.42
k31 (per h)c0.04
  • a Dosage forms selected in GastroPlus for simulations.

  • b Predicted by ADMET predictor or default values in GastroPlus.

  • c Population PK analysis of human intravenous data.