TABLE 1

In vivo and in vitro data used for risk assessment

Inactivator	P450	Inactivator Dose	Object Drug	AUC Change of Object Drug (Observed)	K_I	k_inact	λ/k_deg Using Total C_max	λ/k_deg Using Unbound C_max	References^{^a}
					μM	min⁻¹
Amiodarone	3A4	400 mg, q.d., 4 days	Simvastatin acid	1.8	42	0.02	7.8^*	0.3^*	Becquemont et al., 2007; Shoaf et al., 2005; Mori et al., 2009
Amprenavir	3A4	1200 mg, b.i.d., 10 days	Rifabutin	2.9	0.3	0.73	3268	2876	Polk et al., 2001; Ernest et al., 2005
Cimetidine	2D6	300 mg, q.i.d., 6 days	Imipramine	2.7	77	0.03	15	12	Wells et al., 1986; Kosoglou et al., 2000; Madeira et al., 2004
Clarithromycin	3A4	500 mg, b.i.d., 9 days	Simvastatin	10	5.5	0.07	133	36	Jacobson, 2004; van Haarst et al., 1998; Mayhew et al., 2000
Clopidogrel	2B6	75 mg, b.i.d., 4 days	Bupropion	1.4	1.4	1.9	78	4.7	Turpeinen et al., 2005; Kim et al., 2008; Walsky and Obach, 2007
Dasatinib	3A4	100 mg, single	Simvastatin	1.2	6.3	0.03	5.8	0.4	Product Label^{^b}; Li et al., 2009
Diltiazem	3A4	60 mg, t.i.d., 2 days	Buspirone	5.3	3.7	0.07	37.6	11	Lamberg et al., 1998; Shum et al., 1996; Zhang et al., 2009
Erythromycin	3A4	500 mg, t.i.d., 2 days	Simvastatin	6.2	11	0.05	57.0	12	Kantola et al., 1998; Olkkola et al., 1993; McConn et al., 2004
Fluoxetine	3A4	20 mg, q.d., 21days	Alprazolam	1.3	5.3	0.02	3.8	0.2	Hall et al., 2003; Harvey and Preskorn, 2001; Mayhew et al., 2000
Isoniazid	3A4	90 mg, b.i.d., 4days	Triazolam	1.5	228	0.08	9.7^*	9.7^*	Ochs et al., 1983; Dattani et al., 2004; Wen et al., 2002
Mibefradil	3A4	100 mg, single	Midazolam	8.9	2.3	0.40	553	4.0	Veronese et al., 2003; Welker et al., 1998
Nelfinavir	3A4	1250 mg, b.i.d., 14days	Simvastatin	6.1	0.48	0.22	952	77	Hsyu et al., 2001; Fang et al., 2008; Ernest et al., 2005
Paroxetine	2D6	20 mg, q.d., 17days	Atomoxetine	7.1	3.6	0.13	25	1.3	Belle et al., 2002; Perloff et al., 2009
Ritonavir	3A4	600 mg, single	Saquinavir	112	0.038	0.29	1315	913	Hsu et al., 1998; Luo et al., 2003
Rofecoxib	1A2	25 mg, q.d., 4 days	Tizanidine	12	4.8	0.07	44	6.7	Backman et al., 2006; Karjalainen et al., 2006
Saquinavir	3A4	1200 mg, t.i.d., 5 days	Midazolam	5.2	0.2	0.31	1223	102	Palkama et al., 1999; Cook et al., 2004; Ernest et al., 2005
Tadalafil	3A4	20 mg, q.d., 14 days	Lovastatin	1.12	12	0.21	76^*	4.9^*	Ring et al., 2005; Wrishko et al., 2008
Ticlopidine	2B6	250 mg, b.i.d., 4 days	Bupropion	1.6	0.3	0.43	1067^*	174^*	Turpeinen et al., 2005; Lu et al., 2006; Walsky and Obach, 2007
Ticlopidine	2C19	200 mg, q.d., 8 days	Omeprazole	6.2	9.2	0.25	108	2.7	Ieiri et al., 2005; Lu et al., 2006; Atkinson et al., 2005
Tienilic acid	2C9	250 mg, q.d., 19 days	(S)-Warfarin	2.9	12.5	0.13	846	30	O'Reilly, 1982; Dubb et al., 1979; Hutzler et al., 2009
Verapamil	3A4	80 mg, t.i.d., 2 days	Simvastatin	4.7	4.6	0.43	195	21	Kantola et al., 1998; Johnson et al., 2001; Wang et al., 2004
Zileuton	1A2	800 mg, b.i.d., 5 days	Theophylline	1.9	117	0.04	16	1.2	Granneman et al., 1995; Lu et al., 2003

↵* The inactivator concentration was calculated with dose normalization.
↵a References for in vivo AUC change, in vivo inactivator concentration (in cases where C_max was not measured in the DDI study), and in vitro MBI parameters.
↵b http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021986s009s010lbl.pdf.