Table 3 GSK2256098 and trametinib pharmacokinetic parameters after repeat dosing on Day 15

From: A phase Ib dose-finding, pharmacokinetic study of the focal adhesion kinase inhibitor GSK2256098 and trametinib in patients with advanced solid tumours

 

Cmax, ng/mL Geometric mean (%CV)

tmax, h Median (range)

AUC(0–τ), ng·h/mL Geometric mean (%CV)

GSK2256098 pharmacokinetics when given in combination with trametinib (whole blood)

GSK2256098 250 mg (n = 10)

1397 (71)

2.0 (1.5–4.1)

5467 (58)

GSK2256098 500 mg (n = 21)

2453 (82)

2.0 (1.5–6.0)

10 410a (62)

GSK2256098 pharmacokinetics when given in combination with trametinib (dry blood spot)

GSK2256098 250 mg (n = 6)

1229 (73)

2.8 (1.5–4.1)

4975 (57)

GSK2256098 500 mg (n = 10)

2834 (44)

2.0 (1.5–4.0)

12 663 (27)

Trametinib pharmacokinetics when given in combination with GSK2256098 (plasma)

Trametinib 0.25 mg + GSK2256098 500 mg BID (n = 6)

6.23 (17)

2.5 (0.33–6.5)

122 (15)

Trametinib 0.375 mg + GSK2256098 500 mg BID (n = 6)

11.2 (47)

2.5 (2.0–6.0)

229 (43)

Trametinib 0.5 mg + GSK2256098 250 mg BID (n = 10)

16.3 (35)

2.4 (0.50–6.5)

347b (33)

Trametinib 0.5 mg + GSK2256098 500 mg BID (n = 6)

13.0 (27)

2.6 (0.62–4.8)

266 (26)

Trametinib 1.0 mg + GSK2256098 500 mg BID (n = 3)

36.0 (11)

1.5 (1.5–6.5)

732 (22)

Trametinib pharmacokinetics when given as monotherapy (plasma) 16

Trametinib 2.0 mg (n = 13)

22.2 (28)

1.75 (1.0–3.0)

370c (22)

  1. AUC area under the concentration-time curve over the dosing interval, BID twice daily, Cmax, maximal plasma concentration, QD once daily, tmax time to Cmax, % CV between-subject coefficient of variation
  2. an = 20
  3. bn = 8
  4. cAUC in this study was reported as 0–24 h
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