Table 5

Effect of isoform-selective CYP inhibitors/substrates on the formation of 5-HOS by human liver microsomes

Inhibitor	μM	CYP Isoforms Inhibited	% of Control Activity
			Subject I.D.
			FGL852	EFE556	HGD057	FAG771	Mean	SD
α-Naphthoflavone	5	1A2	77.0	81.0	83.0	76.0	79.3	3.3
8-Methoxypsoralen	20	2A6	86.2	64.9	88.6	69.5	77.5	11.8
Retinol	100	2C8	34.0	58.4	35.0	111.9	59.8	36.6
Sulfaphenazole^5-a	5	2C9/10	ND^5-b	51.0	89.6	44.0	61.5	24.6
Tienilic acid	100	2C9/10	74.5	44.5	43.1	43.8	51.6^5-c	15.3
Tolbutamide	1000	2C8/9/10	64.9	71.0	ND	38.1	58.0	17.6
S-Mephenytoin	500	2C19	80.7	86.2	101.4	58.9	81.8	17.4
Quinidine	2	2D6	144.5	91.7	144.9	ND	127.3	30.6
4-Methylpyrazole	20	2E1	101.8	83.0	127.5	ND	104.3	22.6
Ketoconazole^5-a	5	3A	30.0	63.3	33.2	84.1	52.5^5-c	25.8
Troleandomycin	200	3A	48.7	98.4	68.3	85.3	75.0	21.2
Nifedipine^5-a	25	3A/2C	41.9	57.4	ND	22.4	40.6^5-c	17.5
Ketoconazole + sulfaphenazole	5	3A	19.8	54.2	29.5	73.4	44.3^5-c	23.9
	5	2C9/10
Ketoconazole + tienilic acid	5	3A	11.0	36.1	17.7	42.9	26.8^5-c	14.6
	100	2C9/10

↵5-a IC₅₀ values for the inhibition of 5-HOS formation in FGL852 microsomes by ketoconazole, sulfaphenazole, and nifedipine were 2.9, 1.9, and 9.7 μM, respectively.
↵5-b ND, not determined.
↵5-c p < 0.05.