Table 4.
Pharmacokinetics of Naldemedine in the Hepatic Impairment Study
| Mild (n = 8) | Moderate (n = 8) | Normal Function (n = 8) | |
|---|---|---|---|
| Plasma | |||
| AUC0‐t (ng·h/mL) | |||
| Geometric mean (CV%) | 19.1 (36.4) | 24.2 (21.7) | 23.1 (22.8) |
| Arithmetic mean (SD) | 20.2 (7.8) | 24.7 (5.1) | 23.6 (5.5) |
| AUC0‐inf (ng·h/mL) | |||
| Geometric mean (CV%) | 19.6 (35.9) | 24.8 (21.8) | 23.6 (22.8) |
| Arithmetic mean (SD) | 20.7 (7.8) | 25.3 (5.3) | 24.1 (5.6) |
| Cmax (ng/mL) | |||
| Geometric mean (CV%) | 2.44 (47.4) | 2.93 (16.8) | 2.71 (26.3) |
| Arithmetic mean (SD) | 2.67 (1.27) | 2.96 (0.50) | 2.80 (0.77) |
| Tmax (h)a | 0.75 (0.50, 2.00) | 0.63 (0.50, 0.75) | 0.75 (0.50, 1.00) |
| t½,z (h) | |||
| Geometric mean (CV%) | 14.0 (15.1) | 13.3 (21.5) | 13.5 (9.3) |
| Arithmetic mean (SD) | 14.1 (2.1) | 13.6 (2.9) | 13.6 (1.3) |
| CL/F (L/h) | |||
| Geometric mean (CV%) | 10.2 (35.9) | 8.1 (21.8) | 8.5 (22.8) |
| Arithmetic mean (SD) | 10.7 (3.4) | 8.2 (1.8) | 8.7 (1.8) |
| Urine | |||
| Feu0‐72 (%) | |||
| Geometric mean (CV%) | 11.5 (20.9) | 17.2 (25.5) | 18.7 (15.9) |
| Arithmetic mean (SD) | 11.7 (2.4) | 17.7 (4.2) | 18.9 (3.0) |
| CLR (L/h) | |||
| Geometric mean (CV%) | 1.2 (23.0) | 1.4 (26.7) | 1.6 (19.2) |
| Arithmetic mean (SD) | 1.2 (0.3) | 1.5 (0.3) | 1.6 (0.3) |
| Serum | |||
| At 0.75 h | |||
| Cunbound (ng/mL) | |||
| Geometric mean (CV%) | 0.188 (52.8) | 0.244 (34.1) | 0.210 (27.9) |
| Arithmetic mean (SD) | 0.207 (0.089) | 0.257 (0.098) | 0.217 (0.057) |
| Ctotal (ng/mL) | |||
| Geometric mean (CV%) | 2.21 (57.5) | 2.88 (22.3) | 2.81 (32.4) |
| Arithmetic mean (SD) | 2.47 (1.15) | 2.94 (0.61) | 2.94 (0.98) |
| Fu (%) | |||
| Geometric mean (CV%) | 8.5 (15.8) | 8.5 (24.4) | 7.5 (10.1) |
| Arithmetic mean (SD) | 8.6 (1.4) | 8.7 (2.4) | 7.5 (0.8) |
| At 24 h | |||
| Cunbound (ng/mL) | |||
| Geometric mean (CV%) | 0.0227 (36.8) | 0.0283 (52.2) | 0.0214 (27.9) |
| Arithmetic mean (SD) | 0.0241 (0.0089) | 0.0313 (0.0142) | 0.0221 (0.0061) |
| Ctotal (ng/mL) | |||
| Geometric mean (CV%) | 0.239 (45.6) | 0.324 (36.7) | 0.287 (29.3) |
| Arithmetic mean (SD) | 0.260 (0.124) | 0.340 (0.103) | 0.298 (0.087) |
| Fu (%) | |||
| Geometric mean (CV%) | 9.5 (25.1) | 8.8 (20.0) | 7.5 (10.4) |
| Arithmetic mean (SD) | 9.8 (2.4) | 8.9 (1.8) | 7.5 (0.8) |
AUC0‐t indicates area under the plasma concentration‐time curve from time 0 to the time of the last quantifiable concentration after dosing; AUC0‐inf, area under the plasma concentration‐time curve extrapolated from time 0 to infinity; CL/F, apparent total clearance; CLR, renal clearance; Cmax, maximum observed plasma concentration; Ctotal, total concentration; Cunbound, unbound concentration; CV%, coefficient of variation; Feu0‐72, fraction excreted in urine from time 0 to 72 hours postdose; Fu, serum protein unbound fraction; Tmax, time to maximum plasma concentration; t½,z, terminal elimination half‐life.
a
Median (minimum, maximum).