TABLE 3

IC₅₀ values of CYP3A4/5 inhibitors

The effect of known inhibitors on the formation rate of tritiated water and 6β-hydroxytestosterone (6OHBT) was determined using as substrate either [1,2,6,7-³H]testosterone or [6β-³H]testosterone, in the presence of the indicated concentrations of unlabeled testosterone (Test.). IC₅₀ values were calculated from full inhibition curves with at least eight concentration points. Data are mean values ± S.E.M. or half-range from two to four experiments. Compound A is a Merck proprietary compound.

Inhibitor	IC₅₀
		Tritiated Water Formation
		[1,2,6,7-³H]Testosterone			[6β-³H]Testosterone (60 μM Test.)	6OHBT Formation (60 μM Test.)
		10 μM Test.	60 μM Test.		[6β-³H]Testosterone (60 μM Test.)	6OHBT Formation (60 μM Test.)
	μM
Ketoconazole	0.026 ± 0.006	0.031 ± 0.001	0.01 ± 0.01	0.023 ± 0.003
Miconazole	0.12 ± 0.01	0.12 ± 0.01	0.06 ± 0.01	0.10 ± 0.01
Bromocriptine	0.43 ± 0.03	1.5 ± 0.2	1.2 ± 0.3	1.4 ± 0.01
Nicardipine	0.80 ± 0.03	0.29 ± 0.06	0.23 ± 0.04	0.21 ± 0.08
Compound A	11.5 ± 0.3	7.8 ± 0.3	8.3 ± 0.9	6.9 ± 0.9
Nifedipine	17.2 ± 4.7	12.7 ± 2.3	12.4 ± 3.1	11.5 ± 0.5