Mean enzyme kinetic parameters of the formation of 5-hydroxylansoprazole and lansoprazole sulfone from R- and S-lansoprazole from the cDNA-expressed P450s R- and S-lansoprazole were incubated for 60 min with 20 nmol of each cDNA-expressed P450 isoform.
Metabolite | CYP2C9 | CYP2C19 | CYP3A4 | |
|---|---|---|---|---|
| R-Enantiomer | ||||
| V max a | Hydroxy | 78.6 ± 6.3 | 1850.9 ± 157.8 | 97.4 ± 14.5 |
| Sulfone | 416.8 ± 19.6 | |||
| K m | Hydroxy | 66.4 ± 14.2 | 13.1 ± 2.5 | 27.1 ± 0.6 |
| Sulfone | 38.4 ± 0.5 | |||
| Clint | Hydroxy | 1.2 ± 0.2 | 143.3 ± 15.7 | 3.6 ± 0.5 |
| Sulfone | 10.8 ± 0.6 | |||
| Total Clint | 1.2 | 143.3 | 14.4 | |
| S-Enantiomer | ||||
| V max | Hydroxy | 134.7 ± 10.7 | 404.8 ± 2.7 | 83.1 ± 11.1 |
| Sulfone | 1149.4 ± 71.3 | |||
| K m | Hydroxy | 15.9 ± 2.0 | 2.3 ± 0.2 | 32.1 ± 9.6 |
| Sulfone | 15.0 ± 0.9 | |||
| Clint | Hydroxy | 9.0 ± 0.5 | 179.6 ± 13.5 | 2.7 ± 0.4 |
| Sulfone | 76.5 ± 0.1 | |||
| Total Clint |
| 9.0 | 179.6 | 79.2 |
↵ a Vmax is expressed as pmol/min/pmol of P450 isoform, Km as μM, and Clint as Vmax/Km (μl/min/nmol of P450)