TABLE 4

Summary of cut-off values, confidence interval, and correlation coefficients (R2) of calibration curves for RIS, R3, Cmax/EC50, and AUC/F2

RIS, R₃, C_max/EC₅₀ were calculated using both C_max_-t and C_max_-u. Cut-off values for RIS, R₃, C_max/EC₅₀ and AUC/F₂ were defined as that corresponding to 20% predicted AUC change.

Hepatocyte  Lot No.	Parameters	RIS		R₃		C_max/EC₅₀		AUC/F₂
Hepatocyte  Lot No.	Parameters	C_max-t	C_max-u	C_max-t	C_max-u	C_max-t	C_max-u	AUC/F₂
mRNA Data
Lot 295	Cut-off value^{^a}	0.74	0.017	0.57	0.98	0.94	0.0088	6.2
	95% CI	0.54	0.013	0.20	0.029	0.079	0.00084	7.0
	R²	0.91	0.97	0.91	0.98	0.97	0.995	0.94
Lot 312	Cut-off value^{^a}	1.32	0.019	0.44	0.98	0.23	0.0056	12
	95% CI	0.28	0.0093	0.062	0.037	0.46	0.0028	3.4
	R²	0.97	0.99	0.97	0.98	0.84	0.99	0.97
Lot 318	Cut-off value^{^a}	0.62	0.011	0.62	0.99	0.33	0.0038	2.3
	95% CI	0.35	0.011	0.18	0.014	0.21	0.0021	2.6
	R²	0.96	0.96	0.97	0.97	0.97	0.97	0.95
Activity Data
Lot 295	Cut-off value^{^a}	0.60	0.017	0.63	0.98	0.62	0.0069	8.8
	95% CI	0.63	0.011	0.28	0.026	0.43	0.0034	5.4
	R²	0.87	0.97	0.87	0.98	0.88	0.98	0.98
Lot 312	Cut-off value^{^a}	0.84	0.013	0.56	0.99	0.58	0.005	4.4
	95% CI	0.37	0.0069	0.13	0.023	0.15	0.0025	2.7
	R²	0.93	0.98	0.93	0.98	0.97	0.99	0.97
Lot 318	Cut-off value^{^a}	0.57	0.0078	0.65	0.995	0.53	0.0052	1.0
	95% CI	0.18	0.0039	0.084	0.020	0.34	0.0025	3.2
	R²	0.97	0.99	0.97	0.98	0.96	0.99	0.78

CI, confidence interval.
↵^a Values were either over- or underpredicted on the basis of the 0.9 cut-off value provided in the 2012 FDA draft guidance.