TABLE 2.
Kinetic parameters (mean ± S.D.) for the formation of 8-hydroxyefavirenz from efavirenz in 15 human liver microsomal samples with CYP2B6*1/*1, CYP2B6*1/*6, and CYP2B6*6/*6 genotypes (n = 5 HLMs for each genotype)
Efavirenz (1–200 μM) was incubated with human liver microsomal samples (0.25 mg/ml) with CYP2B6*1/*1, CYP2B6*1/*6, and CYP2B6*6/*6 genotypes (n = 5 HLM 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 8-hydroxyefavirenz were estimated by fitting the velocity versus efavirenz concentrations to the simple single-site Michaelis-Menten equation. In vitro Clint was calculated as Vmax/Km. The kinetic parameters (Vmax, Km, and Clint) for each genotype group are listed in Supplemental Table 1. The data presented here are mean ± S.D. calculated from five individual HLM values for each genotype.
| HLMs | 8-Hydroxyefavirenz |
||
|---|---|---|---|
| Vmax | Km | Clint | |
| pmol · min−1 · mg protein−1 | μM | μl · min−1 · mg protein−1 | |
| CYP2B6*1/*1 | 87.1 ± 87.4 | 11.2 ± 6.7 | 14.5 ± 22.6 |
| CYP2B6*1/*6 | 100.6 ± 143.7 | 15.2 ± 8.0 | 6.4 ± 7.8 |
| CYP2B6*6/*6 | 25.0 ± 6.7 | 24.0 ± 31.3 | 2.4 ± 1.6 |