Simultaneous Quantification of Brigatinib and Brigatinib-Analog in Rat Plasma and Brain Homogenate by LC-MS/MS: Application to Comparative Pharmacokinetic and Brain Distribution Studies

Table 4

Pharmacokinetic parameters of brigatinib and brigatinib-analog after oral administration of 5 mg/kg of brigatinib and brigatinib-analog in male SD rats (mean ± SD, n = 6).

Analytes	Units	Plasma		Brain
		Brigatinib	Brigatinib-analog	Brigatinib	Brigatinib-analog
AUC(0–t)	ng/mL·min (plasma), ng/g·min (brain)	261528.73 ± 86227.28	262436.45 ± 74089.38	58255.81 ± 13725.10	23196.08 ± 4932.95
MRT	min	403.98 ± 12.02	328.55 ± 35.68	449.04 ± 65.44	379.04 ± 5.40
T1/2	min	189.41 ± 20.55	120.78 ± 29.74	319.42 ± 117.05	256.08 ± 40.01
Tmax	min	260.00 ± 30.98	260.00 ± 48.99	330.00 ± 176.98	240.00 ± 0.00
Cmax	ng/mL (plasma), ng/g (brain)	537.85 ± 185.55	734.41 ± 83.06	68.91 ± 21.57	45.84 ± 11.81
Vd	L/kg	5.66 ± 1.94	3.43 ± 0.96	50.47 ± 19.42	119.35 ± 25.58
CL	L/min/kg	0.022 ± 0.010	0.021 ± 0.006	0.101 ± 0.062	0.325 ± 0.057

compared with brigatinib.