Table 3.
Summary of entrectinib and M5 plasma pharmacokinetic parameters with and without coadministration of itraconazole (200 mg QD) or rifampin (600 mg QD) following a single 100 or 600 mg entrectinib dose
| Analyte | PK Parameter a | Entrectinib 100 mg Alone (N = 10) |
Entrectinib 100 mg with Itraconazole (N = 10) |
Ratio of adjusted Geometric Means (90% CI) |
Entrectinib 600 mg Alone (N = 10) |
Entrectinib 600 mg with Rifampin (N = 10) |
Ratio of Adjusted Geometric Means (90% CI) |
|---|---|---|---|---|---|---|---|
| Entrectinib | AUCinf (nM•h) | 6190 (50%) | 36,100 (17%) | 6.04 (4.54, 8.04) | 36,300 (28%) | 8440 (29%) | 0.23 (0.18, 0.30) |
| Cmax (nM) | 358 (35%) | 615 (17%) | 1.73 (1.37, 2.18) | 1810 (25%) | 807 (26%) | 0.44 (0.35, 0.56) | |
| Tmax (h) | 2.0 (1.0, 3.0) | 5.0 (2.0, 8.0) | ND | 3.5 (2.0, 5.0) | 2.0 (2.0, 5.0) | ND | |
| t1/2 (h) | 20.2 (17%) | 49.8 (22%) | ND | 16.7 (16%) | 9.9 (26%) | ND | |
| M5 | AUCinf (nM h) | 1710 (30%) | 4310 (30%) | ND | 11,000 (44%) | 1530 (28%) | ND |
| Cmax (nM) | 52.3 (37%) | 31.5 (42%) | ND | 383 (56%) | 108 (23%) | ND | |
| Tmax (h) | 5.0 (3.0, 5.0) | 6.0 (5.0, 48.0) | ND | 5.0 (4.0, 5.0) | 3.0 (2.0, 6.0) | ND | |
| t1/2 (h) | 40.8 (22%) | 88.0 (32%) | ND | 33.8 (12%) | 31.1 (28%) | ND | |
| M5/Entrectinib ratio | AUCinf | 0.288 (28%) | 0.124 (29%) | ND | 0.337 (56%) | 0.187 (28%) | ND |
| Cmax | 0.151 (26%) | 0.0538 (34%) | ND | 0.234 (59%) | 0.136 (23%) | ND |
AUCinf area under the plasma concentration–time curve extrapolated to infinity, CI confidence intervals, Cmax maximum plasma concentration, ND not done, t1/2 terminal elimination half-life, Tmax time of maximum plasma concentration
aUnadjusted geometric means (geometric coefficients of variation) for all except Tmax which is median (minimum, maximum), and M5/entrectinib ratios which are arithmetic mean (coefficients of variation)
‘Unadjusted’ refers to raw data, and ‘adjusted’ refers to data that have been subjected to statistical analysis. Statistical comparisons were only conducted for entrectinib AUCinf and Cmax