Table 1.
Clinical pharmacokinetics of trametinib after concomitant oral and i.v. administration (2 mg trametinib orally, 5 μg [14C]-trametinib i.v.)
| Parameter (units) | Trametinib (oral) | [14C]-trametinib (i.v.) | Total radioactivity* (i.v.) |
|---|---|---|---|
| tmax† (h) | 1.50 | 0.08 | 0.08 |
| (1.00, 1.58) | (0.08, 0.08) | (0.08,0.08) | |
| Cmax‡ (ng ml–1) | 8.03 | 0.105 | 0.118 |
| [118] | [71] | [54] | |
| (2.56, 24.31) | (0.044, 0.190) | (0.058, 0.177) | |
| AUC(0,t)‡ (ng ml–1 h) | 248 | 0.858 | 1.68 |
| [83] | [57] | [56] | |
| (99.8, 580) | (0.546, 1.76) | (1.18, 3.60) | |
| AUC(0,∞) (ng ml–1 h) | 525 | 1.56 | 4.92§, 5.91§ |
| [36] | [31] | ||
| (333, 783)‡ | (1.26, 2.39)‡ | ||
| t1/2 (h) | 264 | 229 | 643§, 176§ |
| [62] | [39] | ||
| (130, 481)‡ | (144, 348)‡ | ||
| CL or CL/F‡ (l h–1) | 3.81 | 3.21 | ND |
| [36] | [31] | ||
| (2.56, 6.01) | (2.09, 3.97) | ||
| Vss‡ (l) | ND | 976 | ND |
| [79] | |||
| (385, 1836)‡ | |||
| Vd,z‡ (l) | ND | 1060 | ND |
| [75] | |||
| (435, 1985)‡ |
t1/2, half-life; tmax, time to reach Cmax; Vss, volume of distribution at steady state; Vd,z, volume of distribution during the terminal phase.
Total radioactivity concentration units are ng equivalents trametinib ml−1.
tmax results are presented as median (minimum, maximum).
Results are presented as geometric mean [%CV] (minimum, maximum) for n >2.
Elimination half-life and AUC(0,∞) for total radioactivity were estimated in only two of four subjects; individual subject values are listed. AUC(0,∞), area under the concentration–time curve from time zero to infinity; AUC(0,t), area under the concentration–time curve from time zero to time t; CL, systemic clearance; CL/F, apparent oral clearance; Cmax, maximum concentration; ND, not determined.