Table 5.
Summary of digoxin plasma pharmacokinetic parameters with and without coadministration of a single 600 mg dose of entrectinib following a single 75 mg digoxin dose
| Analyte | PK parametera | Digoxin Alone (N = 10) |
Digoxin with Entrectinib (N = 10) |
Ratio of adjusted geometric means (90% Confidence Intervals) |
|---|---|---|---|---|
| Digoxin | AUCinf (nM•h) | 34.2 (14%) | 40.4 (17%) | 1.18 (1.06, 1.32) |
| Cmax (nM) | 1.97 (29%) | 2.52 (39%) | 1.28 (0.98, 1.67) | |
| Tmax (h) | 1.0 (0.5, 1.0) | 2.0 (0.5, 3.0) | ND | |
| t1/2 (h) | 35.9 (15%) | 38.4 (37%) | ND | |
| CLR (mL/min) | 130 (16%) | 123 (13%) | 0.95 (0.91, 0.98) | |
| fe (%) | 40.2 (13%) | 44.0 (14%) | ND |
AUCinf area under the plasma concentration–time curve extrapolated to infinity, CLR renal clearance, Cmax maximum plasma concentration, fe (%) percent of dose excreted unchanged in urine, 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)
‘Unadjusted’ refers to raw data, and ‘adjusted’ refers to data that have been subjected to statistical analysis. Statistical comparisons were only conducted for digoxin AUCinf, Cmax and CLR