Table 2.
Geometric mean pharmacokinetic parameters after a single dose of 40 mg afatinib for subjects with moderate or severe renal impairment and matched healthy controls (as grouped by eGFR)
| Parameter and unit | Moderate renal impairment (n = 8) | Matched controls to moderate renal impairment (n = 8) | Severe renal impairment (n = 8) | Matched controls to severe renal impairment (n = 8) |
|---|---|---|---|---|
| Primary endpoints | ||||
| AUClast (ng·h/mL) | 948 (32.9) | 776 (22.9) | 952 (31.3) | 634 (50.8) |
| C max (ng/mL) | 28.7 (44.0) | 28.4 (32.2) | 28.2 (24.5) | 23.2 (42.1) |
| Secondary endpoint | ||||
| AUC∞ (ng·h/mL) | 976 (32.5) | 797 (22.7) | 980 (31.9) | 653 (49.8) |
| Other endpoints | ||||
| t max (h) | 6.0 (5.0 to 8.0) | 5.0 (5.0 to 6.0) | 5.0 (3.0 to 7.0) | 5.5 (5.0 to 7.0) |
| t 1/2 (h) | 73.4 (21.6) | 81.7 (19.4) | 80.2 (15.9) | 75.5 (28.5) |
| CLR,0–72 (mL/min) | 16.1 (26.8) | 25.4 (46.7)a | 8.7 (46.6)a | 29.6 (25.8)b |
| fe0–72 (%) | 1.65 (26.7) | 2.12 (44.2)a | 0.91 (18.5)a | 2.39 (33.5)b |
| Protein binding (%) | 94.7 ± 0.7 | 94.8 ± 0.2 | 94.4 ± 1.0 | 94.7 ± 0.6 |
Data are presented as geometric mean (geometric CV %) or mean ± SD for protein binding or median (range) for t max
AUC last area under the drug plasma concentration–time curve from time 0 to the time of the last quantifiable data point, AUC ∞ 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
a n = 7
b n = 5