TABLE 5

Predictions of drug interactions for mechanism-based inactivators using IC₅₀ values gathered after a 30-min incubation with or without NADPH and the prediction method applicable for reversible inhibition

Inactivator	Enzyme	Affected Drug	Predicted DDI^a			Actual DDI^b	Reference
Inactivator	Enzyme	Affected Drug				Actual DDI^b	Reference	-NADPH	+NADPH
Diltiazem	CYP3A	Buspirone	1.5	23	5.3	Lamberg et al., 1998
Erythromycin	CYP3A	Buspirone	4.6	57	5.9	Kivisto et al., 1997
Furafylline^c	CYP1A2	Caffeine	5.5	19	∼10	Tarrus et al., 1987
Paroxetine	CYP2D6	Desipramine	1.7	5.1	5.2	Alderman et al., 1997
	CYP3A	Alprazolam	1.0	1.2	0.99	Calvo et al., 2004
Ritonavir	CYP3A	Triazolam	11	22	20	Greenblatt et al., 2000
Ticlopidine	CYP1A2	Theophylline	1.1	2.3	1.6	Colli et al., 1987
	CYP2B6	Bupropion^d	5.8	12	14	Turpeinen et al., 2005
	CYP2C19	Omeprazole	2.2	3.0	2.4	Tateishi et al., 1999
Tienilic acid	CYP2C9	S-Warfarin	2.7	8.7	2.9	O'Reilly, 1982
Verapamil	CYP3A	Midazolam	1.3	6.4	2.9	Backman et al., 1994
Zileuton	CYP1A2	Theophylline	1.4	3.5	1.9	Granneman et al., 1995

↵ a The value for [I]_{in vivo} used in the predictions was the unbound estimated portal vein C_max as described in Obach et al. (2006).
↵ b Clinical interaction data used in this analysis represent the largest reported interaction for each inactivator.
↵ c The free fraction of furafylline in human plasma was unavailable in the scientific literature. A value of 0.39 was measured experimentally using ultrafiltration.
↵ d This represents the effect on hydroxybupropion/bupropion AUC ratio, not parent exposure.