Safety and Pharmacokinetics of Motesanib in Combination with Panitumumab and Gemcitabine-Cisplatin in Patients with Advanced Cancer

Table 3

Pharmacokinetic parameter estimates (Mean ± SD)a of motesanib after single-dose administration in combination with panitumumab and gemcitabine/cisplatin.

Parameter		Motesanib dose cohort
	50 mg QD (𝑛=7−8)	75 mg QD (𝑛=3−6)	100 mg QD (𝑛=2−4)	125 mg QD (𝑛=9−11)	75 mg BIDb (𝑛=2)
𝑡max, h, median (range)	1 (1–3)	1 (1–3)	1.38 (1–3)	1 (1–3)	1 (1–1)
𝐶max, ng/mL (SD)	152 (78)	186 (92)	278 (90)	458 (208)	268 (NR)
AUC0-24, 𝜇g·h/mL (SD)	1.03 (0.50)	1.31 (0.51)	2.38 (NR)	2.82 (1.02)	2.54 (NR)
AUC0-inf, 𝜇g·h/mL (SD)	1.12 (0.52)	1.64 (0.48)	2.59 (NR)	3.05 (1.34)	NR
𝑡1/2,𝑧, h (SD)	6.72 (0.71)	6.52 (2.00)	6.65 (NR)	6.28 (1.60)	5.21 (NR)
CL/F, L/h (SD)	51.1 (17.5)	48.8 (15.6)	38.6 (NR)	50.5 (27.5)	64.3 (NR)
𝐶24, ng/mL (SD)	9.22 (2.85)	13.9 (6.7)	19.9 (NR)	31.0 (22.4)	143 (NR)

AUC_0-inf: area under the plasma concentration-versus-time curve from time 0 to infinite time; AUC_0-24: area under the plasma concentration-versus-time curve from time 0 to 24 hours after dose; BID: twice daily; CL/F: apparent clearance; 𝐶_max: maximum observed concentration after dosing; 𝐶₂₄: observed concentration at 24 hours after dose; NR: not reported; QD: once daily; 𝑡_max: time of maximum observed plasma concentration; 𝑡_1/2,𝑧: estimated terminal elimination half-life.
^a𝑡_max values are reported as median (range).
bFor the 75-mg BID dose cohort, 𝑡_1/2,𝑧 values were estimated based on the terminal slope after the first dose on week 1 or 2, AUC_0-24 values were estimated using 2×AUC_0-12, and CL/F was estimated by total daily dose/(2×AUC_0-12).