Table 3.

Pharmacokinetic parameters of paclitaxel after intravenous and oral administration to wild type (WT) and mdr1a/1b knockout (KO) mice.

		WT			mdr1a/1b KO			WT + WK-X-34		WT + LY335979
		IV	po		IV	po		po		po
			pv	sys		pv	sys	pv	sys	pv	sys
Dose	(mg/kg)	5	20		5	20		20		20
C max	(nM)	---	730	442	---	2523	1179	3018	1631	2258	1208
T max	(h)	---	1	1	---	1	1	0.5	2	0.5	1
AUC	(nM·hr)	2320	2002	1089	2661	6575	3086	10,615	8636	7970	3201
k e	(h−1)		0.43	0.50		0.55	0.35	0.26	0.23	0.53	0.64
t 1/2	(h)	2.38	1.62	1.37	2.12	1.25	2.00	2.69	2.98	1.30	1.09
MRT	(h)	1.71	2.51	2.29	1.47	2.16	3.09	4.15	4.67	2.42	2.25
CL tot	(L/h/kg)	2.52			2.20
Vd ss	(L/kg)	4.32			4.15
BA			11.7			29.0
F a F g			16.6			66.3		36.0		86.8
F h			70.6			45.7

C_max: maximum plasma concentration; T_max: time to maximum plasma concentration; k_e: elimination rate constant; t_1/2: elimination half-life; MRT: mean residence time; F_aF_g: apparent absorption ratio (F_a) intestinal availability (F_g); F_h: hepatic availability.