TABLE 2

In vitro clearance, RAF for P450 isoforms 1A2, 2C9, 2C19, 2D6, and 3A4, and percentage (%) contributions to human liver microsomal metabolism of bortezomib


P450 Isoform

Rate of Metabolism (pmol/min/10 pmol P450)a

RAF

% Contributionb
CYP1A2 0.74 0.628 10.5
CYP2C9 0.07 0.753 1.2
CYP2C19 3.21 0.411 30.1
CYP2D6 1.54 0.202 7.1
CYP3A4
2.92
0.576
38.4
  • a pmol/min/10 pmol P450 for isoforms 1A2, 2C9, 2C19, 2D6, and 3A4; in vitro clearance with HLM: 4.38 pmol/min/0.5 mg microsomal protein

  • b % Contribution = RAF × (CL, CYPn)/(CL, HLM) × 100.