Article Figures & Data
Tables
- 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 Estimate Cytochrome P450 Isoform 6 h 12 h 24 h 48 h mRNA Activity mRNA Activity mRNA Activity mRNA Activity Emax 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) Emax/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)