Table 2.
Geometric mean pharmacokinetic parameters after a single dose of 50 mg afatinib for subjects with mild or moderate hepatic impairment and matched healthy controls
| Parameter and unit | Mild hepatic impairment (n = 8) | Matched controls to mild hepatic impairment (n = 8) | Moderate hepatic impairment (n = 8) | Matched controls to moderate hepatic impairment (n = 8) |
|---|---|---|---|---|
| Primary endpoints | ||||
| AUC0–∞ (ng h/mL) | 886 (53.7) | 956 (22.7) | 934 (31.0) | 985 (32.3) |
| C max (ng/mL) | 33.7 (51.7) | 30.7 (33.7) | 39.5 (40.1) | 31.1 (46.0) |
| Secondary endpoint | ||||
| AUC0–tz (ng h/mL) | 842 (50.8) | 930 (22.5) | 904 (31.4) | 956 (33.3) |
| Other endpoints | ||||
| t amax (h) | 5.0 (0.5–8.0) | 5.0 (3.0–7.0) | 4.0 (0.5–5.0) | 7.5 (5.0–9.0) |
| t 1/2 (h) | 74.9 (47.6) | 60.3 (14.9) | 64.3 (13.1) | 59.9 (28.5) |
| Ae0–72 (mg) | 1.29 (40.5) | 1.21 (14.3) | 1.04 (47.7) | 0.998 (26.6) |
| fe0–72 (%) | 2.58 (40.5) | 2.43 (14.3) | 2.07 (47.7) | 2.00 (26.6) |
| CLR,0–72 (mL/min) | 32.7 (37.6) | 27.2 (26.4) | 24.1 (71.0) | 21.5 (32. 8) |
Ae 0–72 amount of unchanged drug excreted into the urine over 72 h, AUC 0–tz area under the drug plasma concentration–time curve from time 0 to the time of the last quantifiable data point, AUC 0–∞ area under the drug plasma concentration–time curve from time 0 to infinity, C max maximum drug concentration in plasma, CL R,0–72 renal clearance over 72 h, CV % coefficient of variation (%), fe 0–72 fraction of oral dose observed in urine over 72 h, t 1/2 terminal elimination half-life, t max time to reach C max
Results are presented as geometric mean (geometric CV %) unless stated otherwise
aMedian and range