TABLE 1

Kinetic parameters describing the inactivation of P450 2C9 by tienilic acid and (±)-suprofen when different probe substrates are used to measure residual activity

Data were fit to both a hyperbolic equation (eq. 1) and the Hill equation (eq. 2), as described under Materials and Methods. Efficiency of inactivation was calculated as the ratio of k_inact to K_I.

Inactivator	Substrate	k_inact	K_I	n	Efficiency
		min^-1	μM		ml/min/μmol
Tienilic acid	(S)-Flurbiprofen^a	0.18	19.2	1.6	9.4
	Diclofenac^a	0.17	20.1	2.1	8.5
	(S)-Warfarin^b	0.13	12.5		10.4
(±)-Suprofen	(S)-Flurbiprofen^a	0.03	24.2	1.4	1.2
	Diclofenac^a	0.03	26.6	1.3	1.1
	(S)-Warfarin^b	0.02	6.7		3.0

↵ a Data for the inactivation of both (S)-flurbiprofen and diclofenac 4-hydroxylation were best fit to eq. 2 (the Hill equation).
↵ b Data for the inactivation of (S)-warfarin 7-hydroxylation were best fit to eq. 1.