TABLE 6

Shifted IC₅₀ values and IC₅₀ ratios corrected for observed microsomal binding

All IC₅₀ values are rounded to two significant figures.

Inhibitor	Enzyme	Total Inhibitor Concentration			Unbound Inhibitor Concentration (fu_mic)
Inhibitor	Enzyme	IC₅₀ No Dilution^{^a}	IC₅₀ 10-Fold Dilution^{^b}	IC₅₀ Ratio^{^c}	IC₅₀ No Dilution	IC₅₀ 10-Fold Dilution	IC₅₀ Ratio^{^c}
		μM
Ticlopidine	CYP2B6	0.047	0.39	0.12	0.033	0.076	0.43
Tienilic acid	CYP2C9	0.066	0.57	0.12	0.066	0.50	0.13
S-Fluoxetine	CYP2C19	5.3	14	0.38	2.9	3.1	0.94
Paroxetine	CYP2D6	0.050	0.53	0.094	0.022	0.075	0.29
Azamulin	CYP3A4	0.038	0.31	0.12	0.037	0.23	0.16
Mibefradil	CYP3A4	0.027	0.61	0.044	0.010	0.10	0.10

↵a IC₅₀ values from experiments conducted without a dilution step after a preincubation of inhibitor with NADPH-fortified HLM. Preincubations (30 min) and subsequent marker substrate reactions (5 min) were conducted with 0.1 mg/ml HLM for all enzymes, except CYP3A4 (0.05 mg/ml), with [S] = K_m.
↵b IC₅₀ values from experiments conducted with a 10-fold dilution step after a preincubation of inhibitor with NADPH-fortified HLM. Preincubations (30 min) were conducted with 1.0 mg/ml HLM for all enzymes, except CYP3A4 (0.5 mg/ml). After a 10-fold dilution step, marker substrate reactions (5 min) were conducted with one tenth the concentration of HLM in the preincubation with [S] = K_m.
↵c Shifted IC₅₀ no dilution/shifted IC₅₀ with a 10-fold dilution.