TABLE 2

Metabolites formed by human liver microsomes and cDNA-expressed human P450 isozymes

ID	Retention Time (min)	m/z	Human Plasma Level	% Conversion (% of Total Radioactivity Profile)
				HLM		CYP3A4		CYP3A5		2D6	2C19	1A2	1A1	2B6	4F3A
				5 μM	20 μM	5 μM	20 μM	5 μM	20 μM	5 μM	5 μM	5 μM	5 μM	5 μM	5 μM
M1	13.7	552	N.D.^{^a}	N.D.	1.80	N.D.	0.33	2.68	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
M3	16.2	554	Trace^{^b}	N.D.	N.D.	5.20	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
M4	16.6	368	Trace	4.20	1.10	4.57	0.58	2.22	<0.81	N.D.	0.29	0.29	0.33	0.22	0.24
M5	17.6	552	Trace	7.70	1.10	3.81	0.80	0.90	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
M8	19.2	538	Trace	N.D.	1.10	N.D.	N.D.	N.D.	N.D.	N.D.	0.49	N.D.	N.D.	N.D.	N.D.
M9	19.7	552	Trace	7.12	1.10	4.99	1.59	3.01	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
M10	20.2	554	Trace	N.D.	N.D.	N.D.	5.35	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
M11	20.3	536	Trace	8.08	11.0	1.12	5.35	21.32	10.67	2.74	N.D.	N.D.	N.D.	N.D.	N.D.
M14	21.7	552	Trace	10.12	<4.79	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
M15	22.2	367	Minor^{^c}			<3.45	<4.64	15.74	2.87	1.90	N.D.	1.37	2.90	2.06	0.61
M16	22.5	536	Trace			<3.45		15.74	2.87	1.90	N.D.	N.D.	N.D.	N.D.	N.D.
M18	22.9	552	Trace	<6.39	N.D.	3.24		1.32	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
M21	26.9	536	Trace	6.00	9.70	0.32	<4.56	15.34	9.38	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
M22	27.2	538	Minor	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	0.83	N.D.	N.D.	N.D.	N.D.
M23	29.9	536	Minor	<9.21	<12.8	1.12	<7.99	<7.94	<6.02	0.38	N.D.	N.D.	N.D.	N.D.	N.D.
M24	33.1	536	Minor	2.42	<2.68	0.25	1.27	6.96	2.39	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
M25	34.2	536	Trace	0.13	0.36	N.D.	N.D.	0.82	0.25	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
M28	40.1	522	Major^{^d}	N.D.	0.60	N.D.	BIT	N.D.	BIT	0.56	0.38	0.34	0.57	0.90	1.78
M30	41.2	522	Major	N.D.	N.D.	N.D.	N.D.	N.D.	BIT	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
Boceprevir (SCH 534128)	42.8	520	Major	0.21	26.12^{^e}	BIT	37.98^{^e}	0.98	38.77	57.22	60.3	59.66	55.46	56.54	57.31
M31	43.1	522	Major	N.D.	26.12^{^e}	N.D.	37.98^{^e}	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
Boceprevir (SCH 534129)	44.6	520	Major	0.31	17.42	BIT	18.98	2.19	19.67	31.66	30.71	31.72	33.40	33.77	34.35
M32	48.8	463	Trace	N.D.	0.35	N.D.	0.97	0.11	0.88	N.D.	1.06	2.18	2.32	1.29	0.65

↵a ID, identification; HLM, human liver microsomes; N.D., not detected; BIT, below integration threshold of radiometric detector but detected by mass spectrometer. Only metabolites detected in human plasma are listed in the table. Sum of boceprevir = SCH 534128 + SCH 534129.
↵b Trace is defined as the percent ratio of extracted ion chromatogram (XIC) area for the metabolites (all known isomers) to that for parent (two isomers) is ≤10%.
↵c Minor is defined as the percent ratio of XIC area for the metabolites (all known isomers) to that for parent (two isomers) is between 10 and 50%.
↵d Major is defined as the percent ratio of XIC area for the metabolites (all known isomers) to that for parent (two isomers) is ≥50%.
↵e M31 is a minor component coeluting with boceprevir.