Table 4.

The pharmacokinetic parameters of panobinostat in FVB wild-type, PKO (Mdr1a/b^−/−), BKO (Bcrp1^−/−), and TKO (Mdr1a/b^−/−Bcrp1^−/−) mice after the administration of a single intravenous dose of 10 mg/kg Standard error of K_p is calculated via propagation of error.

Parameter	Unit	WT			TKO			PKO			BKO
		Plasma	Brain	Spinal Cord	Plasma	Brain	Spinal Cord	Plasma	Brain	Spinal Cord	Plasma	Brain	Spinal Cord
Dose	mg/kg	10			10			10			10
t1/2	h	13.6	21.9	18.1	13.5	12.5	8.8	10.4	11.7	9.1	N.D.a	10.4	11.3
CL	L/h per kg	9	—	—	6.6	—	—	9.3	—	—	10.6	—	—
Vss	L/kg	57.5	—	—	42.8	—	—	50.3	—	—	17.6	—	—
AUCinf	ng*h/mL	1113 ± 87	1515 ± 45	848 ± 41	1519 ± 59	6562 ± 162	4765 ± 159	1073 ± 40	3770 ± 112	2286 ± 54	943 ± 44	892 ± 19	569 ± 20
AUCinf % extrapolated		8.6	48.6	38.0	9.0	24.6	13.3	6.5	23.1	15.1	5.3	33.5	59.6
Kp		—	1.36 ± 0.11	0.76 ± 0.07	—	4.32 ± 0.20	3.14 ± 0.16	—	3.51 ± 0.17	2.13 ± 0.09	—	0.95 ± 0.05	0.6 ± 0.04
Kp,uu		—	0.32	0.21	—	1.02	0.87	—	0.83	0.59	—	0.22	0.17
DAfree			1	1		3.17	4.12		2.58	2.80		0.69	0.79

CL, clearance; N.D., not determined; t_1/2, half-life.

^aPlasma half-life of panobinostat in BKO mice was not determined because of the lack of concentration information to characterize the terminal phase.