Table 3

Contributions of CYP2C19 and CYP3A4 to CIT N-demethylation estimated by RAFs in human liver microsomes

HLRAF3-aCLContribution3-b
CYP2C19CYP3A4CYP2C193-cCYP3A43-cHLMCYP2C19CYP3A4
pmol P450/mg nmol P450/mg μl/mg/min μl/mg/min μl/mg/min % %
510.50.380.2573.153.617.1187.15
67.90.170.1911.412.417.9258.49
305.90.160.1431.322.037.0364.72
80.60.130.0151.071.720.9062.44
220.90.130.0221.072.071.0851.55
291.10.280.0282.313.670.7562.99

The clearances of CIT N-demethylation by recombinant CYP2C19 (CLrec-CYP2C19) and CYP3A4 (CLrec-CYP3A4) were 24.4 and 8.34 μl/nmol P450/min, respectively.

  • 3-a RAFs for CYP2C19 and CYP3A4 were calculated as described in “Materials and Methods.”

  • 3-b Expressed as percentage of CLCYP2C19 and CLCYP3A4 in the first-order rate clearance by human liver microsomes (CLHLM) for CIT N-demethylation in each microsomal preparation.

  • 3-c The clearances by CYP2C19 (CLCYP2C19) and CYP3A4 (CLCYP3A4) were estimated as follows: CLCYP2C19 = CLrec-CYP2C19 × RAFCYP2C19 and CLCYP3A4 = CLrec-CYP3A4 × RAFCYP3A4.