TABLE 7

Effects of decreasing microsomal protein on the shifted IC₅₀ values and magnitude of the IC₅₀ shifts for extensively metabolized MDIs

IC₅₀ shift experiments were performed by preincubating selected inhibitors with HLM at the stated concentrations for 30 min with or without NADPH. After the preincubation step, marker substrate reactions (5 min) were initiated by the addition of marker substrate ([S] = K_m) without the incorporation of a dilution step. All values were rounded to two significant figures.

Inhibitor	P450 Enzyme	[HLM]	IC₅₀ − NADPH	IC₅₀ + NADPH	IC₅₀ Shift^{^a}
		mg/ml	nM
Ticlopidine	CYP2B6	0.1	180	47	3.8
		0.01	220	11	20
Tienilic acid	CYP2C9	0.1	1000	66	15
		0.01	520	13	40
Paroxetine	CYP2D6	0.1	730	51	15
		0.01	880	25	35
Azamulin	CYP3A4	0.05	210	38	5.5
		0.005	330	13	25
Mibefradil	CYP3A4	0.05	930	27	34
		0.005	650	23	28

↵a IC₅₀ shift represents the IC₅₀ value − NADPH/IC₅₀ value + NADPH.