Table 3.
Plasma daprodustat metabolite pharmacokinetic parameters on Day 14/15
| Analyte | Parameter | Normal | CKD Stage 3/4 | HD DD | HD ND | PD |
|---|---|---|---|---|---|---|
| GSK2391220 (M2) | C max (ng/mL) | 8.7 (1.9) | 10.9 (3.6) | 11.3 (6.0) | 15.4 (4.5) | 13.2 (4.5) |
| t max (h) | 3.00 (2.0–4.0) | 4.02 (3.0–4.0) | 2.00 (3.0–6.0) | 4.00 (3.0–6.0) | 4.00 (4.0–6.0) | |
| AUC (0−τ) (ng·h/mL) | 42.4 (10.1) | 98.4 (50.1) | 102.5 (47.0) | 214.5 (84.3) | 191.3 (69.5) | |
| t½ (h) | 3.08 (1.11) | 8.51 (4.47) | 10.02 (2.42) | 8.96 (1.24) | 10.28 (2.29) | |
| %DRM | 11.07 (2.08) | 14.83 (3.08) | 14.86 (3.68) | 19.33 (2.92) | 17.58 (2.59) | |
| GSK2531403 (M3) | C max (ng/mL) | 8.5 (1.8) | 11.4 (3.7) | 12.4 (6.1) | 16.2 (4.6) | 16.1 (6.4) |
| t max (h) | 3.00 (2.0–4.0) | 4.02 (3.0–6.0) | 2.00 (2.0–8.0) | 5.00 (4.0–8.0) | 6.00 (4.0–6.0) | |
| AUC (0−τ) (ng·h/mL) | 43.6 (10.9) | 123.4 (69.6) | 129.1 (60.8) | 268.0 (97.3) | 278.8 (115.9) | |
| t½ (h) | 3.04 (1.03) | 14.48 (11.68) | 15.62 (4.63) | 11.71 (3.20) | 14.98 (4.85) | |
| %DRM | 11.38 (2.23) | 18.44 (4.80) | 18.78 (4.38) | 24.40 (2.70) | 25.13 (5.64) | |
| GSK2487818 (M4) | C max (ng/mL) | 7.1 (1.7) | 8.3 (2.9) | 7.6 (3.6) | 10.7 (2.7) | 9.8 (5.4) |
| t max (h) | 2.00 (2.0–3.0) | 3.50 (2.0–4.0) | 2.00 (2.0–8.0) | 3.50 (2.0–4.0) | 4.00 (3.0–4.0) | |
| AUC (0−τ) (ng·h/mL) | 25.5 (6.0) | 43.4 (20.7) | 43.5 (20.8) | 73.6 (36.4) | 74.4 (31.5) | |
| t½ (h) | 1.78 (0.58) | 3.56 (2.62) | 3.36 (0.79) | 3.95 (1.32) | 3.79 (0.95) | |
| %DRM | 6.60 (0.98) | 6.57 (1.61) | 6.23 (1.20) | 6.56 (1.40) | 6.76 (1.34) | |
| GSK2506102 (M5) | C max (ng/mL) | 2.1 (0.4) | 2.8 (1.0) | 3.0 (1.5) | 3.9 (1.2) | 4.1 (1.5) |
| t max (h) | 3.00 (2.0–4.0) | 4.02 (3.0–6.0) | 2.00 (3.0–6.0) | 6.00 (4.0–8.0) | 4.80 (4.0–6.0) | |
| AUC (0−τ) (ng·h/mL) | 10.7 (2.8) | 34.0 (21.3) | 33.1 (17.5) | 68.6 (25.0) | 74.9 (30.7) | |
| t½ (h) | 2.52 (0.73) | 9.52 (5.40) | 21.3 (9.11) | 13.94 (3.53) | 19.14 (8.10) | |
| %DRM | 2.80 (0.67) | 5.05 (1.71) | 5.19 (1.05) | 6.30 (0.83) | 6.81 (1.34) | |
| GSK2531398 (M6) | C max (ng/mL) | 4.1 (0.9) | 5.1 (1.8) | 4.1 (1.8) | 6.6 (1.7) | 5.9 (2.4) |
| t max (h) | 3.00 (2.0–4.0) | 4.02 (3.0–6.0) | 2.00 (2.0–12.0) | 4.00 (3.0–6.0) | 4.00 (4.0–6.0) | |
| AUC (0−τ) (ng·h/mL) | 18.7 (4.3) | 42.9 (25.9) | 35.4 (17.8) | 78.0 (34.5) | 76.9 (28.1) | |
| t½ (h) | 2.19 (0.51) | 4.78 (1.91) | 7.11 (2.19) | 6.61 (0.93) | 7.32 (2.48) | |
| %DRM | 4.89 (0.87) | 6.31 (1.58) | 5.58 (0.93) | 7.01 (1.10) | 7.05 (0.99) | |
| GSK2531401 (M13) | C max (ng/mL) | 6.0 (1.3) | 7.7 (2.6) | 6.1 (3.7) | 8.2 (3.4) | 11.1 (2.0) |
| t max (h) | 3.00 (3.0–4.0) | 4.02 (3.0–6.0) | 2.00 (0.5–2.2) | 8.00 (6.0–16.0) | 8.00 (6.0–12.0) | |
| AUC (0−τ) (ng·h/mL) | 34.1 (12.2) | 102.1 (54.9) | 77.4 (35.0) | 159.0 (70.2) | 215.6 (41.6) | |
| t½ (h) | 2.73 (0.60) | 10.60 (5.25) | 35.44 (13.27) | 15.28 (2.63) | 27.63 (10.98) | |
| %DRM | 8.55 (2.22) | 15.54 (8.04) | 12.94 (5.42) | 15.42 (7.10) | 20.66 (5.73) |
Values expressed are arithmetic mean (SD) except tmax which is given as median (range). DD, dialysis day.