TABLE 2

Formation activities of oxidative metabolites of [¹⁴C]apixaban (25 μM, n = 3) by human cDNA-expressed P450 enzymes

Human cDNA-expressed P450 enzymes were incubated with 25 μM apixaban in the presence of NADPH at 37°C for 60 min. Data are means ± S.D.

P450 Enzyme	M2	M2^a	M4	M4^a	M7	M7^a
	pmol/min/pmol P450	pmol/min/mg mpe	pmol/min/pmol P450	pmol/min/mg mpe	pmol/min/pmol P450	pmol/min/mg mpe
CYP1A2	0.52 ± 0.18	19.19 ± 6.64	0.01 ± 0.0098	0.45 ± 0.36	0.01 ± 0.004	0.50 ± 0.15
CYP2A6	0	0	0.01 ± 0.001	0.41 ± 0.04	0.01 ± 0.003	0.42 ± 0.08
CYP2B6	0.01 ± 0.001	0.10 ± 0.01	0.02 ± 0.005	0.17 ± 0.04	0.01 ± 0.001	0.09 ± 0.005
CYP2C8	0.04 ± 0.017	0.73 ± 0.33	0.02 ± 0.007	0.39 ± 0.14	0.01 ± 0.001	0.13 ± 0.13
CYP2C9	0.06 ± 0.019	3.32 ± 1.15	0.01 ± 0.001	0.82 ± 0.00.07	0.01 ± 0.002	0.33 ± 0.14
CYP2C18	0.01	1.03	0	0	0	0
CYP2C19	0.05 ± 0.00.009	0.46 ± 0.08	0.02 ± 0.003	0.16 ± 0.03	0.02 ± 0.009	0.18 ± 0.08
CYP2D6	0.02 ± 0.00.004	0.13 ± 0.03	0.02 ± 0.005	0.13 ± 0.04	0.01 ± 0.003	0.05 ± 0.02
CYP2E1	0	0	0	0	0	0
CYP2J2	0.27 ± 0.06	0	0	0	0	0
CYP3A4	0.18 ± 0.04	13.68 ± 3.23	0.06 ± 0.02	4.23 ± 1.38	1.32 ± 0.44	100.19 ± 33.69
CYP3A5	0.03 ± 0.024	0.03 ± 0.024	0.04 ± 0.03	0.04 ± 0.03	1.85 ± 0.74	1.85 ± 0.74
CYP3A7	0.01 ± 0.00	N.A.	0.01 ± 0.00	N.A.	0.02 ± 0.01	N.A.

mpe, human liver microsomal protein-equivalent; N.A., not applicable because of unknown contents of CYP3A7.
↵a Normalized enzyme activity represents activity in the expressed enzyme (picomoles per minute per picomole) × concentration of the enzyme in HLM (picomoles of P450 per milligram of protein). Enzyme concentrations in HLM used for normalization were 37, 29, 7, 19, 60, 9, 7, 76, and 1 pmol/mg of microsomal protein for CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, and 3A5, respectively (Shimada et al., 1994; Rodrigues, 1999; Rostami-Hodjegan and Tucker, 2007).