TABLE 3.

KTZ and ITZ as inhibitors of MDZ, TST, terfenadine, and vincristine metabolism

The data are presented as the mean ± S.D. (n = 3 determinations).

Substrate	P450	Substrate Conc.a	IC50b		CYP3A5/CYP3A4 IC50 Ratio
			KTZ	ITZ	KTZ	ITZ
		µM	nM	nM
MDZ	rCYP3A4	1.4 (0.8)	40 ± 10	240 ± 50	5.0c	9.6
		0.1 (0.06)	2.0 ± 0.2	17 ± 3	8.5d	8.8
	rCYP3A5	2.7 (0.9)	200 ± 4	2300 ± 400
		0.2 (0.07)	17 ± 3	150 ± 60
TST	rCYP3A4	78 (1.0)	9.0 ± 1	40 ± 7	4.4	33
		4.0 (0.05)	17 ± 1	45 ± 3	4.7	9.1
	rCYP3A5	67 (1.0)	40 ± 6	1300 ± 400
		3.0 (0.04)	80 ± 7	410 ± 180
Terfenadine	rCYP3A4	2.4 (0.7)	90 ± 5	900 ± 200	2.2	2.3
		0.2 (0.06)	8.2 ± 1	23 ± 4	1.3	2.8
	rCYP3A5	1.2 (0.8)	200 ± 5	2100 ± 500
		0.1 (0.07)	6.5 ± 2	64 ± 14
Vincristine	rCYP3A4	75 (1.0)	150 ± 30	360 ± 50	0.8	1.9
		4.0 (0.05)	111 ± 10	29 ± 4	0.6	1.7
	rCYP3A5	45 (1.0)	120 ± 10	680 ± 230
		2.0 (0.04)	70 ± 10	50 ± 5

Conc., concentration.

^a[S]/K_m ratio in parentheses.

^bIC₅₀ was determined at a [S] close to the K_m (S₅₀) and at a [S] below K_m (S₅₀) (see Table 2).

^cIC₅₀ ratio at higher [S].

^dIC₅₀ ratio at lower [S].