P450 | Relative Contribution of the Isoform to the total P450 Contents in Liver Microsomes (Fraction)* | Relative Contribution of the Isoform to Thioridazine Metabolism in Liver Microsomes (Percentage)† | ||||||
---|---|---|---|---|---|---|---|---|
Thioridazine Mono-2-sulfoxidation | Thioridazine Di-2-sulfoxidation | Thioridazine 5-Sulfoxidation | Thioridazine N-Demethylation | |||||
CYP1A2 | 0.127a | 10.8 | 16.7 | 46.5 | 44.1 | |||
CYP2A6 | 0,040a | N.D. | N.D. | 3.5 | N.D. | |||
CYP2B6 | 0.002a | 0.2 | N.D. | 0.2 | N.D. | |||
CYP2C9 | 0.180b | 6.6 | N.D. | 8.2 | N.D. | |||
CYP2C19 | 0.010b | 12.1 | 6.1 | 0.4 | 2.7 | |||
CYP2D6 | 0.015a | 48.6 | 63.6 | 0.9 | 1.6 | |||
CYP2E1 | 0.066a | N.D. | N.D. | 6.0 | N.D. | |||
CYP3A4 | 0.288a | 21.7 | 13.6 | 34.3 | 56.1 |
N.D., not detected.
↵* Data according to a Shimada et al. (1994) and b Lewis (2001).
↵† Relative contribution of P450s to the particular metabolic pathways of thioridazine was calculated as percentage of the sum of predicted velocities in liver microsomes. The predicted velocity in liver microsomes was calculated by multiplying the velocity in Supersomes (see Fig. 5) by the relative contribution of isoform to the total P450 content in liver microsomes. For details, see Wójcikowski et al. (2003, 2004).