TABLE 1

Kinetic parameters for the formation of 8-hydroxyefavirenz from efavirenz and 4-hydroxybupropion from bupropion in expressed CYP2B6.1 and CYP2B6.6 without and with coexpression of Cyt b5

Kinetic data are presented as mean ± S.D. (n = 3 incubations were performed in duplicate). In vitro Cl_int was calculated as V_max/K_m. Kinetic parameters for the formation of 8-hydroxyefavirenz and 4-hydroxybupropion were estimated by fitting the velocity versus substrate concentrations to the simple single-site Michaelis-Menten equation.

Kinetic Parameters	Without Cyt b5		With Cyt b5		P Value (Comparing with vs. without b5)^†
Kinetic Parameters	CYP2B6.1	CYP2B6.6	CYP2B6.1	CYP2B6.6	CYP2B6.1	CYP2B6.6
Efavirenz 8-hydroxylation
V_max, pmol · min⁻¹ · pmol⁻¹	1.21 ± 0.15	1.61 ± 0.11^**	1.02 ± 0.11	0.95 ± 0.02	0.14	0.00002
K_m, μM	3.2 ± 1.0	8.8 ± 1.6^***	3.4 ± 0.6	6.2 ± 2.6	0.74	0.14
Cl_int, μl · min⁻¹ · pmol⁻	0.39 ± 0.08	0.19 ± 0.04^**	0.30 ± 0.06	0.17 ± 0.07	0.18	0.69
Bupropion 4-hydroxylation
V_max, pmol · min⁻¹ · pmol⁻¹	13.37 ± 0.97	18.55 ± 0.82^**	15.18 ± 0.99	11.77 ± 1.46^**	0.04	0.0002
K_m, μM	64.2 ± 13.4	62.6 ± 7.3	90.6 ± 10.3	110.0 ± 29.8	0.02	0.02
Cl_int, μl · min⁻¹ · pmol⁻¹	0.21 ± 0.03	0.30 ± 0.03^**	0.17 ± 0.02	0.11 ± 0.04^*	0.07	0.0002

↵* P < 0.05,
↵** P < 0.01, and
↵*** P < 0.001 compared CYP2B6.6 to CYP2B6.1 without and with coexpression of Cyt b5, respectively.
↵† Kinetic parameters of CYP2B6.1 with and without Cyt b5 as well as CYP2B6.6 with and without Cyt b5 were also compared.