TABLE 4

Enzyme induction interactions, in vitro to in vivo translation

Perpetrator	Induction Effect	C_max (µM)	AUC Ratio	C_max Ratio	In Vivo Victim	Reference
Apremilast	Approximately 0.65-fold in activity at 10 µM (CYP1A2)	0.8				FDA, 2014aa
	0.30-fold in activity at 100 µM (CYP2C9)
	3.7-fold, approximately50% of rifampin in activity at 100 µM (CYP3A4)		0.84	0.90	Norgestimate^{^b}
Belinostat	2.3-fold and 14% of omeprazole in activity at 15 µM (CYP1A2)	100				FDA, 2014b
Ceftolozane	0.27-fold in mRNA and 0.39-fold in activity at 1000 µg/ml (CYP1A2^{^a})	97.3	1.07	0.99	Caffeine^{^c}	FDA, 2014al
	0.36-fold in mRNA and 0.60-fold in activity at 1000 µg/ml (CYP2B6^{^a})
	0.26-fold in mRNA and 0.70-fold in activity at 1000 µg/ml (CYP3A4)		1.23	1.14	Midazolam^{^c}
Ceritinib	6.03-fold in mRNA and 2.06-fold in activity (1 donor) at 2.5 µM (CYP3A4^{^a})	1.8				FDA, 2014ao
	1.18-fold in mRNA and 2.31-fold in activity (1 donor) at 1 µM (CYP2C9)
Idelalisib	46% of positive control in mRNA at 10 µM (CYP2B6)	4.6				FDA, 2014an
	3.9-fold in mRNA at 10 µM (CYP2C8^{^a})
	3.1-fold in mRNA at 10 µM (CYP2C9)
	54% of positive control in mRNA at 10 µM (CYP3A4)
	2.4-fold in mRNA at 10 µM (UGT1A1^{^a})
	2.1-fold in mRNA at 10 µM (UGT1A4)
Ledipasvir	4.08-fold at 10 µM and 71% of weak activator androstanol (PXR)	0.4				FDA, 2014k
	2.0-fold at 1 µM in mRNA, 2-fold at 10 µM in activity (CYP2B6)		0.79	0.79	Efavirenz^{^c}
			1.06	0.93	Efavirenz
	2.6-fold at 1 µM and >10-fold at 10 µM in mRNA, 1.32-fold at 1 µM and >5-fold at 10 µM in activity (CYP3A4^{^a})		1.33	1.06	Atazanavir^{^c}
			1.2	1.44	Ethinyl estradiol
Olaparib	3.2-fold and 40% of phenobarbital in activity at 30 µM (CYP2B6)	18.2				FDA, 2014s
Pirfenidone	2.20-fold in activity at 250 µM (CYP2C19)	48.8				FDA, 2014i
	1.87-fold in activity at 250 µM (CYP3A4^{^a})
Suvorexant	4.8-fold and 20.4% of omeprazole in mRNA at 5 µM, 2.7-fold and 10.7% of omeprazole in activity at 20 µM (CYP1A2^{^a})	1.0				FDA, 2014c
	2.4-fold and 18.6% of phenobarbital in mRNA at 5 µM, 2.3-fold and 23.1% of phenobarbital in activity at 20 µM (CYP2B6^{^a})
	22.0-fold and 42.7% of rifampin in mRNA at 5 µM, 0.4-fold in activity at 20 µM (CYP3A4^{^a})		1.47	1.23	Midazolam
	33% of rifampin at 10 µM (PXR)
Tasimelteon	16.5-fold in mRNA and 5-fold in activity at 100 µM (CYP2B6)	0.8				FDA, 2014l
	4.43-fold and 60.3% of rifampin in activity at 100 µM (CYP2C8)		1.03	1.01	Rosiglitazone
	2.27-fold and 83.2% of rifampin in activity at 100 µM (CYP3A4^{^a})		0.9	0.94	Midazolam
Metabolite M12	4.64-fold in mRNA and 2.71-fold (1 donor) in activity at 100 µM (CYP1A2^{^a})
	12-fold in mRNA and 8-fold in activity at 100 µM (CYP2B6)
Tazobactam	0.46-fold in mRNA and 0.63-fold in activity at 1250 µg/ml (CYP1A2)	55.9	1.07	0.99	Caffeine^{^c}	FDA, 2014al
	0.60-fold in mRNA and 0.65-fold in activity at 1250 µg/ml (CYP2B6)
	0.44-fold in mRNA and 2.9-fold (12% of rifampin) in activity at 1250 µg/ml (CYP3A4^{^a})		1.23	1.14	Midazolam^{^c}
Metabolite M1	0.15-fold in mRNA and 0.16-fold in activity at 75 µg/ml (CYP1A2)
	0.062-fold in mRNA and 0.11-fold in activity at 75 µg/ml (CYP2B6)
	0.47-fold in mRNA and 0.67-fold in activity at 75 µg/ml mRNA 3/3 donors (CYP3A4)
Vorapaxar	2.97-fold in activity at 30 µM (CYP1A2)	0.05				FDA, 2014am
	4.66-fold in activity at 30 µM (CYP2B6)
	300% activation at 30 µM (CYP2E1)

R₃ values were not provided for any of the compounds listed.
↵^a Inhibition was also observed of the same enzyme.
↵^b Metabolite norelgestromin was measured.
↵^c Perpetrator was administered as the combination drug.