Table 2.
Regorafenib pharmacokinetics
| PK parameters | Regorafenib (phase A) | Regorafenib + Esomeprazole concomitant (phase B) | Regorafenib + Esomeprazole 3 hours prior (phase C) | Relative difference B vs. A (95% CI) | P value | Relative difference C vs. A (95% CI) | P value |
|---|---|---|---|---|---|---|---|
| Regorafenib | |||||||
| AUC0–24h (μg·hour/mL (CV)) | 55.9 (40.3) | 53.7 (33.5) | 53.6 (42.6) | −3.9% (−20.5 to 16.1%) | 1.00 | −4.1% (−22.8 to 19.2%) | 1.00 |
| Cmax (μg/mL (CV)) | 5.3 (28.6) | 4.4 (24.2) | 4.7 (25.5) | −16.5% (−34.9 to 7.0%) | 0.18 | −12.1% (−32.0 to 13.8%) | 0.45 |
| Tmax (median hours (IQR)) | 2.5 (2.0–3.0) | 2.5 (2.0–3.0) | 3.0 (2.5–3.1) | 1.00 | 0.83 | ||
| M‐2 | |||||||
| AUC0–24h (μg·hour/mL (CV)) | 36.6 (71.4) | 35.1 (66.2) | 35.0 (64.5) | −4.0% (−28.6 to 29.2%) | 1.00 | −4.3% (−30.1 to 31.0%) | 1.00 |
| Cmax (μg/mL (CV)) | 2.9 (72.0) | 2.6 (60.9) | 2.6 (44.2) | −11.0% (−38.7 to 29.1%) | 0.88 | −9.3% (−38.1 to 32.9%) | 1.00 |
| Tmax (median hours (IQR)) | 3.3 (2.0–6.0) | 2.6 (2.1–3.5) | 3.5 (2.5–6.0) | 1.00 | 1.00 | ||
| M‐5 | |||||||
| AUC0–24h (μg·hour/mL (CV)) | 21.9 (103.4) | 21.6 (125.7) | 20.0 (128.9) | −1.4% (−22.5 to 25.4%) | 1.00 | −8.9% (−40.4 to 39.1%) | 1.00 |
| Cmax (μg/mL (CV)) | 1.6 (118.8) | 1.4 (132.4) | 1.4 (107.6) | −10.4% (−34.6 to 22.8%) | 0.78 | −9.1% (−43.2 to 45.5%) | 1.00 |
| Tmax (median hours (IQR)) | 2.6 (1.5–4.0) | 2.3 (1.5–8.0) | 3.5 (2.5–6.0) | 1.00 | 0.76 | ||
AUC0–24h, 0–24‐hour area under the concentration‐time curve (expressed as geomean μg·hour/mL (CV)); CI, confidence interval; Cmax, peak plasma concentration (expressed as geomean μg/mL (CV)); CV, coefficient of variation expressed in %; IQR, interquartile range; PK, pharmacokinetic; Tmax, time until maximum concentration (expressed as median hours (IQR)).