TABLE 3

Summary of AFE comparing Emax, EC50, or Emax/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 (Emax, EC50, or Emax/EC50) Determined at 6, 12, 24, or 48 h Compared with Estimate at 72 h
Parameter EstimateCytochrome P450 Isoform6 h12 h24 h48 h
mRNAActivitymRNAActivitymRNAActivitymRNAActivity
Emax AFE (n)CYP1A20.33 (7)0.10 (6)0.42 (8)0.35 (7)0.77 (10)0.48 (8)0.89 (10)0.81 (13)
CYP2B60.42 (20)0.10 (7)0.59 (15)0.21 (9)0.64 (18)0.45 (10)0.96 (18)0.90 (13)
CYP2C90.49 (2)0.84 (3)0.94 (4)1.0 (4)
CYP3A40.29 (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)CYP1A20.93 (5)0.32 (6)0.64 (8)1.1 (7)1.24 (10)0.56 (7)0.75 (10)0.94 (12)
CYP2B61.82 (19)1.2 (8)1.99 (12)1.3 (9)1.30 (18)1.0 (11)1.07 (18)1.0 (12)
CYP2C92.0 (1)1.1 (3)ND2.4 (3)0.70 (4)ND
CYP3A41.8 (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)
Emax/EC50 AFE (n)CYP1A20.32 (5)0.34 (4)0.32 (8)0.54 (5)0.35 (10)0.68 (7)0.45 (8)0.84 (11)
CYP2B60.21 (18)0.083 (8)0.20 (11)0.16 (9)0.52 (17)0.42 10)0.95 (16)0.94 (13)
CYP2C90.19 (1)0.77 (3)0.43 (3)1.4 (4)
CYP3A40.22 (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)