Dose level	No. enrolled	Cmax, mean ± SD, μg/L	Tmax, mean ± SD, hours	AUC0–8, mean ± SD, hours * μg/L	AUCall, hours * μg/mL
Sorafenib run‐in	9	1.36 ± 0.937	9.67 ± 10.8	7.78 ± 4.93	22.1 ± 12.6
Sorafenib on enzalutamide	9	0.597 ± 0.434	10 ± 9.98	3.40 ± 2.09	9.29 ± 6.91

PK/PD Legend: These results indicate that the combination of sorafenib and enzalutamide alters the pharmacokinetics of sorafenib. Seven of the nine subjects have samples collected for both cycles of the study. Two subjects had no C2 samples, which did not allow comparisons to be made between C1 and C2 in these cases. Of the seven remaining subjects with C1/C2 samples, six exhibited a significant decrease in C_max and AUC_0–8hrs for sorafenib when coadministered with enzalutamide. The percentage change from C1 to C2 in C_max and AUC_0–8hrs for sorafenib is −58.7% (−35.9% to −79.9%) and − 59.7% (−18.4% to −82.8%), respectively. This suggests that enzalutamide enhances the metabolism of sorafenib through possible induction of CYP3A4.

Abbreviations: Cmax, concentration maximum; Tmax, time of maximum concentration; AUC, area under the curve; PK/PD, pharmacokinetics/pharmacodynamics.