Input parameters of three CYP3A4 inducers in Simcyp for DDI simulations

Mol. wt. (g/mol)823a236b232b
Log Poctanol:water3.28a2.3b1.47b
Blood/plasma ratio0.9a1.01.0
fu, plasma0.175c0.26d0.7c
Polar surface area (Å2)46.33e78.27e
Number of hydrogen bond donors1e2e
First-order absorption rate constant: Ka (1/h)0.51a1.91f0.48f
Volume of distribution: Vd, ss (l/kg)0.33a1.4d0.54d
HLM CLint for CYP3A4 (μl · min−1 · mg−1)0.69g
HLM CLint for other enzymes (μl · min−1 · mg−1)0.56g
Renal clearance: CLR (l/h)1.2a0d0.07d
Oral plasma clearance: CLpo (l/h)0.3d
Systemic plasma clearance: CLi.v. (l/h)7a
CYP3A4 Ki (μM)18.5h
fu, hepatocytes0.419c0.52c1.0c
  • HLM, human liver microsomes.

  • a Default parameters implemented in Simcyp.

  • b Data from the DrugBank database (

  • c Data from Shou et al. (2008).

  • d Data from Thummel et al. (2006).

  • e Calculated from the software ACD/Labs log D suite.

  • f Predicted by Simcyp using polar surface area and number of hydrogen bond donors.

  • g Data from Pelkonen et al. (2001) and assuming that fm, CYP3A4 for CBZ is 55% based on the clinical DDI data between fluconazole (as a CYP3A4 inhibitor) and CBZ (Nair and Morris, 1999).

  • h Data from Kajosaari et al. (2005).