TABLE 3

Clinical pharmacokinetic and drug-drug interaction data

Category of Clinical Inducer	Interacting Drug	C_max-t	C_max-u	AUC	Victim Drug	Observed  AUC Change	References
		μM	μM	H ⋅ μM		%
Strong, ≥80% decrease in AUC	Rifampicin^{^a}	15	3.6	34	Midazolam	98	Backman et al., 1998;  Kanebratt and Anderson, 2008
	Rifampicin^{^a}	11	2.7	34	Midazolam	95	Eap et al., 2004
	Rifampicin^{^a}	10	2.5	34	Midazolam	97	Fahmi et al., 2012;  Backman et al., 1996a
	Rifampicin^{^a}	6.5	1.6	34	Midazolam	86	Adams et al., 2005
	Phenytoin^{^a}	29	7.3	468	Midazolam	94	Backman et al., 1996b;  Kanebratt and Anderson, 2008
	Carbamazepine^{^a}	21	5.3	1248	Midazolam	94	Backman et al., 1996b;  Kanebratt and Anderson, 2008
	Carbamazepine	25	6.1	1248	Alprazolam	58	Furukori et al.,1998
Moderate, 50–80% decrease  in AUC	Phenobarbital	56	28	1497	Nifedipine	61	Schellens et al., 1989,  Kanebratt and Anderson, 2008
	Troglitazone	3.1	0.031	24	Simvastatin	38	Fahmi et al., 2012;  Prueksaritanont et al., 2001;  Kanebratt and Anderson, 2008
	Troglitazone^{^a}	6.3	0.063	50	Midazolam	67	Fahmi et al., 2012
Weak,  20–50% decrease  in AUC	Terbinafine^{^a}	2.4	0.024	16	Midazolam	25	Ahonen, et al., 1995
	Pleconaril^{^a}	3.0	0.030	42	Midazolam	35	Ma, et al., 2006;  Fahmi and Ripp, 2010
	Pioglitazone	4.5	0.045	44	Simvastatin	−1	Prueksaritanont et al., 2001; Fahmi and Ripp, 2010
	Pioglitazone^{^a}	2.8	0.028	44	Midazolam	26	Fahmi et al., 2012
	Sulfinpyrazone	48	0.96	287	R-Warfarin	22	O'Reilly, 1982;  Kanebratt and Andersson, 2008
	Probenecid	244	24	2705	Carbamazepine	20	Kim et al., 2005; Selen et al., 1982
Clinical  noninducer	Dexamethasone	0.021	0.0054	0.29	Triazolam	19	Fahmi et al., 2012;  Kanebratt and Andersson, 2008
	Nifedipine^{^a}	0.40	0.020	0.87	Midazolam	4	Fahmi et al., 2012; Kanebratt and Andersson, 2008
	Rosiglitazone	1.7	0.0033	8.2	Nifedipine	12	Fahmi et al., 2012;  Harris et al., 1999;  Fahmi and Ripp, 2010
	Rosiglitazone	1.4	0.0028	8.2	Ethinylestradiol	−1	Inglis A et al., 2001;  Fahmi and Ripp, 2010
	Omeprazole	0.74	0.037	1.1	Nifedipine	−25	Soons, et al., 1992;  Kanebratt and Andersson, 2008
	Clotrimazole^{^a}	0.0074	0.0001	NA	Midazolam	9.7	Shord et al., 2010
	Flumazenil	0.0010	0.0005	0.050	Midazolam	−2	Fahmi et al., 2012
	Quinidine	3.3	0.41	42	NA	0	Mihaly et al.,1987;  Leizorovicz et al., 1984

NA, clinical induction interaction data not available.
↵^a Interacting drugs used for preparation of calibration curves.