TABLE 1

P450 activity of human hepatocytes in the presence of ketoconazole in KHB buffer

Ketoconazole was equilibrated with human hepatocytes in KHB to allow nonspecific binding. After equilibration, the extracellular concentration of ketoconazole was measured. The remaining P450 activities in hepatocytes were also determined using the probe substrates.

Ketoconazole in Incubation	Ketoconazole Extracellular	f_A (%)^a
Ketoconazole in Incubation	Ketoconazole Extracellular			CYP1A2	CYP2C9	CYP2C19	CYP2D6	CYP3A4
	μM
100 μM	19.3	2	1	2	9	0
50 μM	9.23	16	4	9	36	0
25 μM	3.98	41	17	31	60	0
12.5 μM	1.48	55	31	59	78	1
6.25 μM	0.640	63	54	71	88	3
3.13 μM	0.263	77	72	82	101	5
1.6 μM	0.153	91	80	83	101	8
0	0	100	100	100	100	100

↵ a f_A (%) = fraction of enzyme activity remaining in the presence of ketoconazole.