Estimated kinetic parameters for the formation of Nor, 3F, and 4F from cisapride and UNK from (±)-norcisapride in human liver microsomes or in heterologously expressed P450 enzymes
| Sample | Nor | 3F | 4F | UNK | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Km2-a | Vmax2-b | Vmax/Km2-c | Km2-a | Vmax2-b | Vmax/Km2-c | Km2-a | Vmax2-b | Vmax/Km2-c | Km2-a | Vmax2-b | Vmax/Km2-c | |
| H112 | 6.00 | 1350 | 225 | 14.3 | 696 | 48.7 | 13.9 | 568 | 40.8 | 107 | 25.1 | 0.24 |
| H093 | 6.90 | 125 | 18.1 | 12.4 | 78.0 | 6.29 | 14.3 | 67.0 | 4.68 | N.D. | N.D. | N.D. |
| CYP3A4 | 3.20 | 5791 | 1810 | 4.30 | 1628 | 378 | 7.90 | 2480 | 313 | 45.5 | 49.5 | 1.09 |
| CYP3A7 | 16.8 | 203 | 12.1 | 18.1 | 16.0 | 0.88 | 25.2 | 28.7 | 1.14 | N.D. | N.D. | N.D. |
| CYP2C8 | 2.00 | 109 | 54.5 | 3.40 | 289 | 85.0 | 5.80 | 26.7 | 4.60 | N.D. | N.D. | N.D. |
H112 and H093 are human liver microsomal samples with high and low CYP3A4/5 activity, respectively.
N.D., not determined.
↵2-a Micromolar.
↵2-b Picomoles per milligram of protein per minute for human liver microsomes, picomoles per nanomole of P450 per minute for cDNA-expressed enzymes.
↵2-c Microliters per milligram of protein per minute for human liver microsomes; microliters per nanomole of P450 per minute for cDNA-expressed enzymes.