Correction to “Considerations from the Innovation and Quality Induction Working Group in Response to Drug-Drug Interaction Guidance from Regulatory Agencies: Guidelines on Model Fitting and Recommendations on Time Course for In Vitro CYP Induction Studies Including Impact on Drug Interaction Risk Assessment”

doi:10.1124/dmd.120.000055err

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TABLE 3

Summary of AFE comparing E_max, EC₅₀, or E_max/EC₅₀ at earlier time points (6, 12, 24, or 48) to 72 h

AFE’s were summarized for each cytochrome P450 isoform and respective inducers: CYP1A2 (omeprazole, phenobarbital), CYP2B6 (efavirenz, phenobarbital, rifampicin), CYP2C9 (rifampicin), CYP3A4 (efavirenz, rifampicin). ND: Not determined.

AFE of Parameter Estimate (E_max, EC₅₀, or E_max/EC₅₀) Determined at 6, 12, 24, or 48 h Compared with Estimate at 72 h
Parameter Estimate	Cytochrome P450 Isoform	6 h		12 h		24 h		48 h
Parameter Estimate	Cytochrome P450 Isoform	mRNA	Activity	mRNA	Activity	mRNA	Activity	mRNA	Activity
E_max AFE (n)	CYP1A2	0.33 (7)	0.10 (6)	0.42 (8)	0.35 (7)	0.77 (10)	0.48 (8)	0.89 (10)	0.81 (13)
	CYP2B6	0.42 (20)	0.10 (7)	0.59 (15)	0.21 (9)	0.64 (18)	0.45 (10)	0.96 (18)	0.90 (13)
	CYP2C9	0.49 (2)	—	0.84 (3)	—	0.94 (4)	—	1.0 (4)	—
	CYP3A4	0.29 (9)	0.22 (4)	0.76 (9)	0.30 (9)	0.90 (12)	0.55 (10)	0.97 (12)	0.90 (10)
	Overall AFE (n)	0.36 (38)	0.13 (17)	0.60 (35)	0.27 (25)	0.76 (44)	0.50 (28)	0.95 (44)	0.87 (36)
	% Within twofold (n)	39 (15)	0 (0)	51 (18)	28 (7)	68 (30)	36 (10)	86 (38)	89 (32)
EC₅₀ AFE (n)	CYP1A2	0.93 (5)	0.32 (6)	0.64 (8)	1.1 (7)	1.24 (10)	0.56 (7)	0.75 (10)	0.94 (12)
	CYP2B6	1.82 (19)	1.2 (8)	1.99 (12)	1.3 (9)	1.30 (18)	1.0 (11)	1.07 (18)	1.0 (12)
	CYP2C9	2.0 (1)	—	1.1 (3)	ND	2.4 (3)	—	0.70 (4)	ND
	CYP3A4	1.8 (8)	1.1 (3)	2.0 (9)	4.1 (9)	1.6 (12)	2.7 (10)	1.1 (10)	1.5 (10)
	Overall AFE (n)	1.64 (33)	0.72 (17)	1.43 (32)	1.89 (25)	1.43 (43)	1.24 (28)	0.96 (42)	1.11 (34)
	% Within twofold (n)	42 (14)	35 (6)	44 (14)	32 (8)	49 (21)	21 (6)	70 (30)	44 (15)
E_max/EC₅₀ AFE (n)	CYP1A2	0.32 (5)	0.34 (4)	0.32 (8)	0.54 (5)	0.35 (10)	0.68 (7)	0.45 (8)	0.84 (11)
	CYP2B6	0.21 (18)	0.083 (8)	0.20 (11)	0.16 (9)	0.52 (17)	0.42 10)	0.95 (16)	0.94 (13)
	CYP2C9	0.19 (1)	—	0.77 (3)	—	0.43 (3)	—	1.4 (4)	—
	CYP3A4	0.22 (7)	0.071 (2)	0.37 (9)	0.076 (8)	0.55 (12)	0.20 (10)	0.94 (10)	0.60 (10)
	Overall AFE (n)	0.23 (31)	0.12 (14)	0.43 (31)	0.16 (22)	0.55 (42)	0.36 (27)	0.99 (38)	0.79 (34)
	% Within twofold (n)	19 (6)	14 (2)	48 (15)	18 (4)	55 (23)	41 (11)	87 (33)	59 (20)