TABLE 1

Nominal EC₅₀ of CYP3A4 mRNA induction corrected for measured and unbound concentration of perpetrator in induction medium

Hepatocyte Lot	Stability		Induction Medium Protein Binding f_u (% Recovery)	E_max	EC₅₀		EC_50,u
Hepatocyte Lot	Average % Remaining^a	% Remaining at 24 h	Induction Medium Protein Binding f_u (% Recovery)	E_max	Nominal^b	Measured^c	Nominal^d	Measured^e
Carbamazepine
NON	100	100	0.89 (95.5)	11	31	31	28	28
Hu1624	100	100		10	23	23	21	21
CDP	100	100		5.3	23	23	21	21
Phenytoin
NON	100	100	0.90 (110)	11	22	22	22	22
Hu1624	100	100		12	25	25	25	25
CDP	100	100		7.7	27	27	27	27
Pioglitazone
NON	62.4	41.3	0.21 (112)	8.8	4.4	2.5	1	0.58
Hu1624	52.2	21.4		7.7	11	6.4	2.5	1.5
CDP	61	35.7		6.9	21	12	4.8	2.8
Pleconaril
NON	20.4	4.5	ND (10.5)	6.6	14	2.5	ND	ND
Hu1624	21.5	6.5		2.9	2.4	0.43	ND	ND
CDP	20.6	7.5		2.5	6.6	1.2	ND	ND
Rifampicin
NON	89.7	70.7	0.61 (105)	23	1.5	1.3	0.92	0.78
Hu1624	89.7	68.7		12	0.28	0.24	0.17	0.15
CDP	87.9	61.7		14	0.36	0.31	0.22	0.19
Rosiglitazone
NON	63.1	42.9	0.15 (111)	17	15	11	2.1	1.5
Hu1624	53.3	24.5		9.3	15	11	2.1	1.5
CDP	64.7	42.5		9.6	22	16	3.1	2.2
Semagacestat
NON	100	100	0.91 (115)	23	2.6	2.6	2.3	2.3
Hu1624	100	100		9.9	1.6	1.6	1.4	1.4
CDP	100	100		17	1.8	1.8	1.6	1.6

f_u, fraction unbound; ND, not determined.
↵^a Average %remaining = C_ave/C₀ × 100%.
↵^b Nominal EC₅₀ is the EC₅₀ value determined based on the nominal concentration of dosing solution (total C₀).
↵^c Measured EC₅₀ is the EC₅₀ value determined based on the measured concentration in induction medium (total C_ave): measured EC₅₀ = nominal EC₅₀ × C_ave/C₀.
↵^d Nominal unbound EC₅₀ (EC_50,u) is the EC₅₀ value determined based on the unbound concentration of dosing solution (C_0,u): unbound EC₅₀ = nominal EC₅₀ × f_u (media).
↵^e Measured EC_50,u is the EC₅₀ value determined based on the measured unbound concentration (C_ave,u): measured EC_50,u = nominal EC₅₀ × f_u (medium) × C_ave/C₀.