CYP2B6 Variant | S-8-Hydroxyefavirenz Formation from S-Efavirenz | R-8-Hydroxyefavirenz Formation from R-Efavirenz | ||||||
---|---|---|---|---|---|---|---|---|
Vmax | n | Clmax | Vmax | n | Clmax | |||
pmol/min per picomoles | μM | ml/min per nanomoles | pmol/min per picomoles | μM | ml/min per nanomoles | |||
CYP2B6.1 | 4.2 ± 0.2 | 7.7 ± 0.6 | 2.1 ± 0.3 | 0.27 | 0.57 ± 0.09 | 16.1 ± 4.4 | 1.5 ± 0.3 | 0.019 |
CYP2B6.4a | 4.5 ± 0.1 | 5.9 ± 0.3 | 2.5 ± 0.2 | 0.39 | 0.78 ± 0.06 | 7.0 ± 1.1 | 1.2 ± 0.1 | 0.071 |
CYP2B6.5 | 3.3 ± 0.1 | 7.3 ± 0.7 | 1.4 ± 0.1 | 0.25 | 0.44 ± 0.02 | 6.5 ± 0.8 | 1.8 ± 0.3 | 0.034 |
CYP2B6.6 | 3.4 ± 0.1 | 11.8 ± 0.5 | 1.8 ± 0.1 | 0.15 | 0.41 ± 0.05 | 14.5 ± 3.8 | 1.2 ± 0.2 | 0.018 |
CYP2B6.7 | 1.5 ± 0.1 | 5.0 ± 0.3 | 1.5 ± 0.1 | 0.16 | 0.14 ± 0.01 | 6.3 ± 1.3 | 1.6 ± 0.4 | 0.011 |
CYP2B6.9 | 1.7 ± 0.1 | 8.1 ± 1.0 | 1.2 ± 0.1 | 0.13 | 0.13 ± 0.03 | 13.5 ± 5.6 | 1.3 ± 0.3 | 0.006 |
CYP2B6.16b | 0.19 ± 0.01 | 0.012 ± 0.002 | ||||||
CYP2B6.17 | 4.4 ± 0.2 | 9.3 ± 0.8 | 1.7 ± 0.2 | 0.24 | 0.38 ± 0.07 | 9.2 ± 4.30 | 1.2 ± 0.3 | 0.055 |
CYP2B6.18b | 0.20 ± 0.01 | 0.009 ± 0.001 | ||||||
CYP2B6.19c | 3.4 ± 0.1 | 13.4 ± 0.9 | 1.5 ± 0.1 | 0.13 | 0.65 ± 0.33 | 31 ± 28 | 1.2 ± 0.4 | 0.013 |
CYP2B6.26 | 1.5 ± 0.1 | 5.0 ± 0.3 | 1.8 ± 0.1 | 0.15 | 0.21 ± 0.01 | 4.2 ± 0.7 | 1.9 ± 0.4 | 0.025 |
↵a CYP2B6.4 (only) showed substrate inhibition with R-efavirenz. Results in the table for CYP2B6.4and R-efavirenz were from the Hill equation and the substrate concentration range 0.11–18 μM. Data were also analyzed with the model for substrate inhibition (LiCata model, x = 3) over the substrate concentration range 0.11–45 μM, yielding Vmax = 0.90 ± 0.18, K = 9.0 ± 3.5, n = 1.1 ± 0.1, Clmax = 0.74, Vi = 0.09 ± 0.19, and Ki = 38 ± 11 μM.
↵b CYP2B6.16 and CYP2B6.18 rates were measured at a fixed substrate concentration of 40 μM S- and R-efavirenz.
↵c For R-efavirenz hydroxylation by CYP2B6.19, an alternative Michaelis-Menten model of linear regression analysis at low substrate concentrations generated a ratio of Vmax/Km = 0.019.