Summary of EC50 and Emax estimates determined by seven IWG member laboratories after treatment of human hepatocytes with prototypical cytochrome P450 inducers for 6, 12, 24, 48, or 72 h. ND: not determined, NC: Not calculated.
| Isoform | Inducer | Parameter | Median and Range (Max to Min) EC50 and Emax Estimates at Each Time Point | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 6 | 12 | 24 | 48 | 72 | ||||||||
| mRNA | Activity | mRNA | Activity | mRNA | Activity | mRNA | Activity | mRNA | Activity | |||
| CYP1A2 | Omeprazole | Median EC50 (μM) (n) Max–Min | 6.2 (3) 3.9–9.1 | 6.0 (4) 2.1–12 | 10.2 (4) 4.9–20 | 5.9 (3) 4.6–7.8 | 15 (6) 7.0–62 | 6.6 (5) 5.8–13 | 13 (6) 9.1–36 | 13 (6) 5.7–200 | 14 (7) 7.1–35 | 40 (7) 3.8–100 |
| Median Emax (fold) Max–Min | 8.2 1.9–20 | 1.6 1.4–2.7 | 8.5 3.9–47 | 4.0 1.9–5.5 | 35 12–133 | 6.8 6.6–23 | 57 17–170 | 13 9.4–59 | 45 28–76 | 18 9.5–59 | ||
| Phenobarbital | Median EC50 (μM) (n) Max–Min | 644 (3) 530–850 | 1200 (2) 160–2100 | 724 (5) 150–1300 | 1500 (4) 760–6100 | 966 (5) 430–1400 | 880 (4) 680–6200 | 924 (5) 91–1100 | 820 (7) 170–4400 | 1090 (5) 120–1470 | 1200 (6) 90–1800 | |
| Median Emax (fold) Max–Min | 1.8 1.3–2.5 | 1.80 1.4–2.2 | 2.3 1.8–2.7 | 2.7 1.9–5.7 | 2.0 1.5–2.5 | 2.7 1.6–3.0 | 2.3 1.7–2.8 | 3.3 2.5–5.2 | 2.9 1.7–3.7 | 3.3 1.8–8.0 | ||
| CYP2B6 | Efavirenz | Median EC50 (μM) (n) Max–Min | 3.6 (7) 1.3–5.8 | 1.6 (1) NC | 2.9 (5) 0.40–23 | NC(0) | 1.9 (5) 0.6–7.5 | NC(0) | 1.4 (6) 0.4–3.1 | 0.76 (2) 0.5–1 | 1.1 (6) 0.5–8.4 | 4.0 (2) 3.9–4.0 |
| Median Emax (fold) Max–Min | 6.4 1.3–18 | 0.63 NC | 9.3 3.1–21 | NC | 7.6 2.8–32 | NC | 9.5 4.2–21 | 3.7 2.4–5 | 9.4 1.6–21 | 5.3 3.8–6.8 | ||
| Phenobarbital | Median EC50 (μM) (n) Max–Min | 450 (7) 120–1600 | 380 (4) 160–25000 | 340 (6) 127–1460 | 560 (5) 310–800 | 260 (7) 120–1900 | 630 (5) 410–1400 | 230 (6) 150–560 | 510 (6) 140–4700 | 305 (7) 28–1100 | 500 (5) 62–3500 | |
| Median Emax (fold) Max–Min | 12 1.3–22 | 2.0 1.5–2.8 | 14 5.1–33 | 2.6 1.3–10 | 18 2.6–58 | 8.1 2.2–29 | 25 6.4–49 | 27 10–40 | 19 8.4–61 | 40 7.7–41 | ||
| Rifampicin | Median EC50 (μM) (n) Max–Min | 1.5 (6) 0.2–2.3 | 2.0 (4) 0.2–3.9 | 1.1 (1) NA | 2.9 (4) 0.2–4.3 | 0.80 (6) 0.1–1.3 | 1.2 (6) 0.18–3.5 | 0.65 (6) 0.3–1.8 | 1.8 (6) 0.73–3.7 | 0.62 (6) 0.5–1.4 | 1.1 (6) 0.5–7.8 | |
| Median Emax (fold) Max–Min | 4.8 1.3–15 | 1.2–2.3 | 8.75 5.3–17 | 4.9 1.4–8.9 | 6.9 1.9–17 | 3.7 1.6–14 | 9.3 5.9–13 | 11 5.6–16 | 11 5.1–15 | 11 8.1–13 | ||
| CYP2C9 | Rifampicin | Median EC50 (μM) (n) Max–Min | 0.2 (1) NC | ND | 0.29 (3) 0.1–0.4 | ND | 1.2 (3) 0.11–8.7 | ND | 0.20 (4) 0.07–0.9 | ND | 0.10 (6) 0.08–1.1 | ND |
| Median Emax (fold) Max–Min | 1.3 1.3–1.4 | ND | 1.9 1.8–5.5 | ND | 2.7 1.8–7.8 | ND | 3.0 2.2–6.6 | ND | 3.3 2.2–4.2 | ND | ||
| CYP3A4 | Efavirenz | Median EC50 (μM) (n) Max–Min | 4.6 (4) 3.5–6.5 | 2.3 (3) 2.0–6.5 | 8.4 (4) 5.1–18 | 11 (4) 3.5–16 | 7.2 (6) 3.1–62 | 13 (4) 4.6–42 | 8.2 (4) 1.0–18 | 4.77 (4) 0.78–13.5 | 3.9 (5) 2.0–19 | 7.90 (4) 0.34–11 |
| Median Emax (fold) Max–Min | 2.2 1.2–25 | 1.8 1.7–2.9 | 8.8 3.5–39 | 5.9 2.7–16 | 11 4.8–30 | 13 4.7–42 | 14 3.7–31 | 11.6 10–120 | 15 9.7–38 | 13.1 6.1–140 | ||
| Rifampicin | Median EC50 (μM) (n) Max–Min | 0.49 (5) 0.06–0.76 | (0)NC | 0.50 (6) 0.38–3.8 | 0.7 (5) 0.12–10 | 0.65 (7) 0.14–1.6 | 0.37 (6) 0.10–40 | 0.43 (6) 0.08–1.1 | 0.28 (6) 0.06–2 | 0.38 (7) 0.04–9.1 | 0.23 (6) 0.02–0.77 | |
| Median Emax (fold) Max–Min | 5.7 2.3–31 | 1.5 NC | 15 3.5–44 | 3.5 1.1–6.6 | 21 4.8–50 | 5.0 2.2–15 | 21 10–50 | 8.2 5.4–29 | 20 5.8–67 | 10.2 5.3–31 | ||
Max, maximum; Min, minimum; NC, Not calculated; ND, not determined.