TABLE 1

Generation of major human metabolites in the hepatocyte relay method compared to suspended and MPCC hepatocytes

Compound Name	Major In Vivo Human Metabolites	Excreta	Circulating Radioactivity^{^a}	Biotransformation Phase	1°/2° metabolite	Metabolites Detected in Matrix
Compound Name	Major In Vivo Human Metabolites	Excreta	Circulating Radioactivity^{^a}	Biotransformation Phase	1°/2° metabolite	Suspended Hepatocytes^{^b}	MPCC^{^c} Hepatocytes^{^d}	Hepatocyte Relay
		%	%
Capromorelin	Nitrocapromorelin^{^e} (A)	11	14	1	2°			Yes
	O-desbenzyl hydroxycapromorelin (B)		12	1	2°		Yes	Yes
	N-desmethyl-O-desbenzyl nitrocapromorelin^{^e} (C)		12	1	2°			Yes
	N-desmethyl-O-desbenzyl hydroxycapromorelin (D)		15	1	2°		Yes	Yes
CP-122721	Desmethyl O-glucuronide	27	14	2	2°	Yes	Yes	Yes
	N-dealkylated, reduced O-glucuronide	11		2	2°
	Desmethylhydroxy O-glucuronide		25	2	2°			Yes
	5-trifluoromethoxysalicylic acid		56	1	2°			Yes^{^f}
Ziprasidone	Sulfoxide	18	69	1	1°	Yes	Yes	Yes
	S-methyldihydroziprasidone	18	69	1	2°	Yes	Yes	Yes
	N-dealkylated sulfoxide	11	21	1	2°		Yes
	N-dealkylated sulfone	11	21	1	2°
Celecoxib	Carboxylic acid	73	20	1	2°	Yes	Yes	Yes
	Carboxylic acid glucuronide		15	2	2°	Yes	Yes	Yes
Linezolid	O-dealkylation/ring opening, carboxylic acid	45		1	2°		Yes	Yes
	N-dealkylation/ring opening, carboxylic acid	10		1	2°		Yes	Yes

↵^a Percentage of total drug-related material radioactivity in circulation.
↵^b Dalvie et al., 2009.
↵^c Micropatterned coculture hepatocytes (7-day incubation).
↵^d Wang et al., 2010.
↵^e Metabolites originally reported as carboxylic acids but later determined to be nitroalkanes (Pfizer internal communication).
↵^f MS negative mode detection only.