TABLE 3.
Kinetic parameters (mean ± S.D.) for the formation of 4-hydroxybupropion from bupropion in 15 human liver microsomal samples with CYP2B6*1/*1, CYP2B6*1/*6, and CYP2B6*6/*6 genotypes (n = 5 HLMs for each genotype)
Bupropion (10–1000 μM) were incubated with HLM samples (0.25 mg/ml) with CYP2B6*1/*1, CYP2B6*1/*6, and CYP2B6*6/*6 genotypes (n = 5 HLMs for each genotype) and a NADPH-generating system at 37°C for 15 min in duplicate. Kinetic parameters (Vmax and Km) for the formation of 4-hydroxybupropion were estimated by fitting the velocity versus bupropion concentrations to the simple single-site Michaelis-Menten. In vitro Clint was calculated as Vmax/Km. The kinetic parameters (Vmax, Km, and Clint) for each genotype group are listed in Supplemental Table 2. The data presented here are mean ± S.D. calculated from five individual HLM values for each genotype.
| HLMs | 4-Hydroxybupropion |
||
|---|---|---|---|
| Vmax | Km | Clint | |
| pmol · min−1 · mg protein−1 | μM | μl · min−1 · mg protein−1 | |
| CYP2B6*1/*1 | 492.8 ± 427.9 | 86.0 ± 75.7 | 18.8 ± 26.3 |
| CYP2B6*1/*6 | 441.6 ± 583.0 | 212.1 ± 221.1 | 21.8 ± 44.2 |
| CYP2B6*6/*6 | 112.9 ± 66.7 | 204.2 ± 66.1 | 0.6 ± 0.5 |