Table 1.
Pharmacokinetic parameters of R406
| (i) Single dose in healthy subjects | Dosage (mg) | Analyte | Tmax (h) | Cmax (ng/mL) | AUC0→∞ (ng·h/mL) | t1/2 (h) | CL/F (L/min) | Vz/F (L) | References |
|---|---|---|---|---|---|---|---|---|---|
| R406 besylate in a TPGS/PG (40:60) solution | 80 (n = 5) | R406 | 1.30 ± 0.27 | 501 ± 128 | 4410 ± 997 | 14.5 ± 3.9 | 0.32 ± 0.07 | 409 ± 175 | [53] |
| 250 (n = 5) | R406 | 1.20 ± 0.27 | 2030 ± 489 | 18,100 ± 2930 | 14.9 ± 3.6 | 0.24 ± 0.04 | 306 ± 94.8 | ||
| 400 (n = 6) | R406 | 1.50 ± 0.27 | 3410 ± 745 | 34,900 ± 14,600 | 17.8 ± 10.6 | 0.22 ± 0.09 | 340 ± 276 | ||
| 500 (n = 5) | R406 | 1.10 ± 0.27 | 3660 ± 713 | 29,600 ± 6270 | 20.9 ± 5.8 | 0.29 ± 0.06 | 546 ± 249 | ||
| 600 (n = 6) | R406 | 1.25 ± 0.27 | 3920 ± 888 | 36,600 ± 7760 | 12.9 ± 5.9 | 0.29 ± 0.09 | 316 ± 146 | ||
| Fostamatinib in an aqueous suspension | 80 (n = 5) | R406 | 1.10 ± 0.22 | 306 ± 46.1 | 3150 ± 982 | 14.8 ± 4.7 | 0.45 ± 0.13 | 557 ± 166 | [53] |
| 250 (n = 5) | R406 | 1.60 ± 0.42 | 1140 ± 122 | 13,700 ± 3140 | 16.0 ± 2.8 | 0.32 ± 0.07 | 431 ± 82.0 | ||
| 400 (n = 5) | R406 | 1.60 ± 0.42 | 1220 ± 317 | 13,400 ± 4360 | 12.1 ± 2.0 | 0.54 ± 0.15 | 545 ± 109 | ||
| Fostamatinib in an aqueous suspension (fasted) | 100 (n = 6) | R406 | 1.17 ± 0.24 | 682 ± 187 | 7510 ± 1560 | 19.0 ± 4.3 | – | – | [53] |
| Fostamatinib in tablet (fasted) | 75 (n = 6) | R406 | 1.39 ± 0.74 | 605 ± 221 | 6490 ± 1750 | 17.9 ± 4.0 | – | – | |
| Fostamatinib in tablet (fed) | 75 (n = 6) | R406 | 3.22 ± 1.62 | 363 ± 94 | 7140 ± 1760 | 18.4 ± 5.0 | – | – |
| (ii) Single dose in special populations | Dosage (mg) | Analyte | Tmax (h) | Cmax (ng/mL) | AUC(0,∞) (ng·h/mL) | t1/2 (h) | CL/F (L/min) | Vz/F (L) | References |
|---|---|---|---|---|---|---|---|---|---|
| Fostamatinib for normal renal function | 150 (n = 8) | R406 | 2.50 | 690 | 6750 | 20.5 | – | – | [57] |
| Fostamatinib for moderate renal function | 150 (n = 8) | R406 | 2.50 | 425 | 6110 | 23.8 | – | – | |
| Fostamatinib for ESKD, post-dialysis dosing | 150 (n = 8) | R406 | 2.25 | 407 | 4950 | 19.6 | – | – | |
| Fostamatinib for ESKD, pre-dialysis dosing | 150 (n = 8) | R406 | 3.00 | 529 | 6280 | 22.1 | – | – | |
| Fostamatinib for normal hepatic function | 150 (n = 8) | R406 | 1.5 | 692 | 8970 | 19.4 | – | – | [57] |
| Fostamatinib for mild (Child-Pugh class A) | 150 (n = 8) | R406 | 2.5 | 615 | 6390 | 16.7 | – | – | |
| Fostamatinib for moderate (Child-Pugh class B) | 150 (n = 8) | R406 | 1.75 | 602 | 6860 | 16.1 | – | – | |
| Fostamatinib for severe (Child-Pugh class C) | 150 (n = 8) | R406 | 1.5 | 582 | 9490 | 19.2 | – | – |
| (iii) Single and multiple dosing in healthy subjects | Dosage (mg) | Analyte | Tmax (h) | Cmax (ng/mL) | AUC(0,∞) (ng·h/mL) | t1/2 (h) | CL/F (L/min) | Vz/F (L) | References |
|---|---|---|---|---|---|---|---|---|---|
| Fostamatinib in an aqueous suspension: day 1 | 160 BID (n = 6) | R406 | 1.25 ± 0.42 | 747 ± 286 | 8250 ± 3970 | 19.9 ± 9.2 | – | – | [53] |
| Fostamatinib in an aqueous suspension: day 7 | 160 BID (n = 6) | R406 | 1.08 ± 0.20 | 1530 ± 534 | 19,900 ± 8750 | – | – | – |
| (iv) Single and multiple dosing in patients with RA | Dosage (mg) | Analyte | Tmax (h) | Cmax (ng/mL) | AUC(0,∞) (ng·h/mL) | t1/2 (h) | CL/F (L/min) | Vz/F (L) | References |
|---|---|---|---|---|---|---|---|---|---|
| Fostamatinib in an aqueous suspension: day 1 | 100 BID (n = 12) | R406 | 1.00 ± 0.37 | 397 ± 177 | 3260 ± 990 | 14.5 ± 4.32 | – | – | [60] |
| Fostamatinib in an aqueous suspension: day 7 | 100 BID (n = 12) | R406 | 1.29 ± 0.40 | 761 ± 234 | NA | 20.4 ± 8.90 | – | – |
AUC0→∞ area under the plasma concentration–time curve from dosing to infinity, BID twice daily, CL/F apparent oral clearance, Cmax maximum concentration, ESKD end-stage kidney disease, Ref. reference, t1/2 terminal elimination half-life, Tmax time to Cmax, TPGS/PG d-alpha-tocopheryl-polyethylene-glycol-1000 succinate/propylene glycol, Vz/F apparent oral volume of distribution, NA not applicable