Table 3.
PK Parameters of Nintedanib and Its Metabolites (PK Set)
| gMean (gCV%) | ||||
|---|---|---|---|---|
| Child‐Pugh A (n = 8) | Child‐Pugh A Matched Healthy Subjects (n = 8) | Child‐Pugh B (n = 8) | Child‐Pugh B Matched Healthy Subjects (n = 8) | |
| Nintedanib | ||||
| tmax a (h) | 4.0 (1.5–6.0) | 4.0 (1.0–6.0) | 3.5 (3.0–8.0) | 3.0 (1.0–8.0) |
| t1/2 (h) | 41.1 (36.5) | 35.0 (31.4) | 42.1 (23.1) | 32.1 (24.5) |
| fe0–72 (%) | 0.204 (96.2) | 0.102 (37.9) | 0.543 (31.7)b | 0.0945 (28.7) |
| CLR0–‐72 (mL/min) | 19.4 (54.6) | 17.2 (39.8)c | 17.6 (47.3)b | 19.5 (26.5)c |
| BIBF 1202 | ||||
| Cmax (ng/mL) | 17.4 (47.1) | 7.55 (56.2) | 60.7 (75.2) | 6.47 (57.5) |
| AUC0–∞ (ng∙h/mL) | 216 (81.8) | 86.8 (48.8) | 1190 (86.4) | 70.4 (38.7) |
| t1/2 (h) | 39.1 (53.8) | 24.7 (65.1) | 46.9 (16.6) | 23.6 (50.1) |
| BIBF 1202 glucuronide | ||||
| Cmax (ng/mL) | 15.1 (113) | 11.4 (62.0) | 19.6 (201) | 12.7 (76.2) |
| AUC0–∞ (ng∙h/mL) | 1040 (95.9) | 657 (66.8) | 2650 (285) | 761 (69.1) |
| t½ (h) | 41.1 (45.5) | 31.9 (34.1) | 57.4 (114) | 28.3 (21.9) |
AUC, area under concentration–time curve in plasma; AUC0–tz, AUC from time 0 to last quantifiable plasma concentration; AUC0–∞, AUC in plasma from time 0 extrapolated to infinity; CLR,t1–t2, renal clearance over time interval from t1 to t2; fet1–t2, fraction of administered drug excreted unchanged in urine over time interval from t1 to t2; gMean, geometric mean; gCV, geometric coefficient of variation; t1/2, terminal half‐life in plasma; tmax, time from last dosing to maximum measured concentration in plasma.
a
Median (min–max); bn = 7; cn = 6.