Single-enzyme kinetic parameters for the N-demethylation of (S)- and (R)-ketamine in insect cell–expressed CYP2B6 and CYP3A4 enzymes and COS-1 cell–expressed CYP2B6 variants
CLint = Vmax/Km, data are medians (range).
| (S)-Ketamine | (R)-Ketamine | |||||
|---|---|---|---|---|---|---|
| Variable | Vmax | Km | CLint | Vmax | Km | CLint |
| pmol/min/pmol CYP (P450) | μM | ml/min/pmol CYP (P450) | pmol/min/pmol CYP (P450) | μM | ml/min/pmol CYP (P450) | |
| Baculovirus-insect cell–expressed CYP (P450) isoforms with coexpression of Cyt b5 | ||||||
| CYP2B6 | 88 (83–90) | 51 (50–54) | 1752 (1567–1797) | 92 (68–101) | 70† (51–78) | 1278† (1248–1415) |
| CYP3A4 | 100 (99–132) | 453 (324–949) | 221 (139–305) | 107 (105–111) | 536 (447–772) | 199 (144–234) |
| COS-1 cell–expressed CYP2B6 variants | ||||||
| CYP2B6.1a | 75 (68–86) | 50 (38–63) | 1466 (1374–1862) | 81 (76–83) | 53 (48–59) | 1519 (1380–1592) |
| CYP2B6.6b | 47∆ (45–49) | 71∆ (64–79) | 663∆ (626–711) | 49∆ (46–50) | 69∆ (66–76) | 699∆ (647–751) |
↵a CYP2B6.1: CYP2B6 wild type protein.
↵b CYP2B6.6: variant carrying amino acid changes Q172H and K262R.
∆Significant difference compared with corresponding values for CYP2B6.1 group Mann-Whitney U test, P < 0.05. †Significant difference compared with corresponding values for (S)-ketamine group, Wilcoxon signed-rank test, P < 0.05.