Table 1.

Comparison of rates of interaction of inhibitors with P450 3A4

Inhibitor	Onset of 7-OBz quinoline O-debenzylation inhibitiona			Spectral binding (SVD)b
	Concentration, μM	Rate (k1), s−1a	t1/2, s	Concentration, μM	k1, s	k2, s−1
Ketoconazole	0.06	0.14 ± 0.01	4.8	15	0.38 ± 0.06	0.32 ±0.07
	0.2	0.87 ± 0.21	0.8
Clotrimazole	0.02	0.39 ± 0.03	1.8	15	0.092 ± 0.01	0.016 ± 0.005
Ritonavir	0.02	0.028 ± 0.001	24	15	0.34 ± 0.10	0.32 ± 0.10
	0.06	0.090 ± 0.003	7.8
Indinavir	2	0.034 ± 0.001	20	15	0.73 ± 0.10	0.61 ± 0.08
	6	0.067 ± 0.001	10
Itraconazole				15	0.30 ± 0.10	0.61 ± 0.08

7-OBz, 7-benzoyl; P450, cytochrome P450; SVD, singular value decomposition.

^aRates are from the traces in Figure 4 fit to the equation y = A(1 − e^−k₁^t) + k_sst (set in GraphPad Prism as Y = A(1 − exp[−Kfast ∗ X] + [Kslow ∗ X])) (78, 79). t_1/2 = 0.693/k₁.

^bFrom the SVD analyses in Figures 9 and S11–S14.