Table 4.
Pharmacokinetic parameters following repeat dose administration of GSK2141795 (days 7, 8, 15, or 22)
| Dose Group (mg) |
AUC(0–24) (ng*hr/mL) |
Cmax (ng/mL) |
Tmax (hours) |
C24 (ng/mL) |
AR | t1/2, eff (hours) |
|---|---|---|---|---|---|---|
|
| ||||||
| Once-daily dosing | ||||||
|
| ||||||
| 10 (n = 2) | (387.0, 555.0) | (24.3, 32.7) | (2.0, 2.0) | (23.8, 33.6) | (3.1, 3.4) | (42.7, 48.1) |
|
| ||||||
| 20 (n = 1) | 1,238 | 90.3 | 3.0 | 42.1 | 5.6 | 84.7 |
|
| ||||||
| 40 (n = 4) | ||||||
| Mean | 3,260.0 | 230.0 | 2.6 | 119.0 | 5.18 | 75.6 |
| [CV, %] | [54] | [36] | [57] | [60] | [66] | |
| (range) | (1,670.0 to 5,464.0) | (128.0 to 339.0) | (2.0 to 5.0) | (72.7 to 234.0) | (2.3 to 10.7) | (29.8 to 169.0) |
|
| ||||||
| 75 (n = 15) | ||||||
| Mean | 6,383.0 | 409.0 | 2.1 | 247.0 | 4.38 | 63.7 |
| [CV, %] | [52] | [50] | [54] | [29] | [33] | |
| (range) | (3,064.0 to 17,060.0) | (170.0 to 1,008.0) | (0.0 to 8.0) | (100.0 to 603.0) | (2.5 to 7.1) | (31.7 to 109.0) |
|
| ||||||
| 100 (n = 3) | ||||||
| Mean | 10,940.0 | 764.0 | 2.0 | 350.0 | 4.91 | 72.6 |
| [CV, %] | [17] | [17] | [26] | [32] | [36] | |
| (range) | (9,354.0 to 13,090.0) | (677.0 to 920.0) | (1.0–2.0) | (253.0 to 430.0) | (3.4 to 6.6) | (47.6 to 102.0) |
|
| ||||||
| 150 (n = 2) | (15,037 to 15,745) | (901 to 932) | (0.0 to 4.0) | (381, 648) | (5.8 to 8.3) | (87.9 to 129) |
| (range) | ||||||
|
| ||||||
| 7 Days on/7 Days off | ||||||
|
| ||||||
| 75 (n = 3) | ||||||
| Mean | 8,723.0 | 574.0 | 2.0 | 304.0 | 7.90 | NA |
| [CV, %] | [25] | [16] | [36] | |||
| (range) | (6,429.0 to 10,746.0) | (482.0 to 659.0) | (1.05 to 3.0) | (191.0 to 406.0) | (2.52 to 24.74) | |
|
| ||||||
| 100 (n = 5) | ||||||
| Mean | 7,342.0 | 439.0 | 4.0 | 281.0 | 4.14 | NA |
| [CV, %] | [63] | [62] | [50] | |||
| (range) | (4,521.0 to 16,262) | (230 to 933) | (0.0 to 7.75) | (180.0 to 482.0) | (3.14 to 5.45) | |
|
| ||||||
| t.i.w. | ||||||
|
| ||||||
| 75 (n = 3) | ||||||
| Mean | 3,143.0 | 191.0 | 3.0 | 113.0 | 2.11 | NA |
| [CV, %] | [31] | [50] | [59] | |||
| (range) | (2,222.0 to 4,256.0 | (115.0 to 322.0) | (0.5 to 3.0) | (76.4 to 212.0) | (1.36 to 3.27) | |
|
| ||||||
| 100 (n = 3) | ||||||
| Mean | 4,502.0 | 268 | 3.0 | 160.0 | 2.49 | NA |
| [CV, %] | [35] | [73] | [32] | |||
| (range) | (3,043.0 to 6,373.0) | (147.0, 583.0) | (1.0 to 5.0) | (112.0 to 220.0) | (2.13 to 2.90) | |
Abbreviations: AUC(0−τ), area under plasma concentration–time curve over 0 to 24 hours; Cmax, maximum observed plasma; Tmax, time of maximum observed plasma; C24, plasma at 24 hours; AR, accumulation ratio; t½, eff, effective half-life; CV, coefficient of variation; NA, not available.