TABLE 5

Relative contributions of in vitro metabolic pathways of four pyrazinone CRF-R1 antagonists in human and rat liver microsomal incubations in the presence of NADPH and GSH

The sample preparation, analysis, and data processing are described under Materials and Methods.

	Relative Contribution %
	BMS-665053		BMS-700557		BMS-707250		BMS-721709

	HLMs	RLMs	HLMs	RLMs	HLMs	RLMs	HLMs	RLMs
Pyrazinone oxidation metabolites	12^a	20^a	11	4	8	7	<1	1
GSH-related adducts on pyrazinone	2^b	5^b	2	3	20	56	<1	<1
Arylamine hydroxylation metabolite	1^c	1^c	1	2	9	29	2	4
GSH-related adducts on arylamine	N.D.	N.D.	<1	<1	N.D.	N.D.	<1	<1

N.D., not determined.
↵a Sum of Met1, Met2, and Met3.
↵b Sum of Met5, Met6, Met7, and Met8.
↵c Met4.