. Author manuscript; available in PMC: 2021 Sep 1.

Published in final edited form as: Clin Cancer Res. 2020 May 15;26(17):4633–4642. doi: 10.1158/1078-0432.CCR-19-3498

Table 3.

Pharmacokinetic parameters of TAK-228 and alisertib alone and in combination across phase I dose levels.

TAK-228 pharmacokinetic parameters
	T_max (h)	C_max (ng/mL)	AUC (ng/mL × h)	Half-life (h)

Run-in dose
1 mg cohort	1 ± 0	7.7 ± 2.6	46.7 ± 13.1	9.8 ± 3.7
2 mg cohort	1.1 ± 0.5	24.2 ± 8.8	172.9 ± 106.9	6.8 ± 4.2
3 mg cohort	1.3 ± 1.1	25.7 ± 9.4	154.5 ± 109.8	6.6 ± 7.8
Combo dose
1 mg cohort	1.2 ± 0.8	8.6 ± 4.2	47.4 ± 13.8	9.1 ± 1.7
2 mg cohort	1.5 ± 1.2	24.7 ± 13.6	128.2 ± 72.7	6.0 ± 2.1
Alisertib pharmacokinetic parameters
	T_max (h)	C_max (ng/mL)	AUC_0–8h (ng/mL × h)	AUC_{ss 0–8h} (ng/mL × h)^a

Run-in dose
30 mg cohort	4.9 ± 3.0	579 ± 202	2,633 ± 607	7,505 ± 1,731
40 mg cohort	10.6 ± 9.5	706 ± 268	2,623 ± 1,566	7,477 ± 4,464
Combo dose
30 mg cohort	1.3 ± 1.6	1,049 ± 363	6,119 ± 2,331^b
40 mg cohort	1.5 ± 1.0	1,306 ± 287	7,672 ± 1508^b

The AUC at steady state (AUC_ss) was estimated using an accumulation factor based on a 12-hour dosing interval and a 20-hour half-life for alisertib as reported in earlier clinical trials.

Since alisertib was dosed twice per day during combination dosing, the AUC_{0–8 h} should be compared with the AUC_{ss 0–8 h} for more accurate comparison.