Table 1.
Neratinib pharmacokinetics after administration of a single oral dose of neratinib 240 mg alone and with multiple oral doses of ketoconazole 400 mg in healthy adults
| Pharmacokinetic variable | Neratinib alone (A) | Neratinib with ketoconazole (B) | Ratio (90% CI) of LS Geometric means (B/A) |
|---|---|---|---|
| Mean (CV%) | Mean (CV%) | ||
| Cmax (ng ml−1) | 55.32 (36) | 201 (58) | 3.21 (2.41, 4.28)*** |
| AUC (ng ml−1 h) | 903 (45) | 4660 (53) | 4.81 (3.59, 6.45)*** |
| tmax (h)† | 6.00 (4.00, 8.00) | 6.00 (3.00, 8.00) | NA |
| Half-life (h) | 11.65 (26) | 18.02 (22) | NA |
| CL/F (l h−1) | 346 (61) | 87.10 (101) | NA |
| Vz/F (l) | 5476 (59) | 2365 (113) | NA |
AUC, total area under the concentration–time curve; CL/F, apparent oral dose clearance; CI, confidence interval; Cmax, peak plasma neratinib concentration; LS, least squares; tmax, time to Cmax; Vz/F, apparent volume of distribution.
***
P < 0.001.
†
Values for tmax are median (range).