TABLE 2

AUC_{plasma (0–2 hr)}, AUC_{brain (0–2 hr)}, K_p,brain and K_p,brain ratios of seven P-gp substrates in WT, Mdr1a/1b-KO and hMDR1-MAC mice

AUC_{plasma (0–2 hour)} and AUC_{brain (0–2 hour)} were calculated using the trapezoidal rule and are shown in ng/ml per hour and ng/g per hour, respectively. K_p,brain is shown in milliliters per gram of the brain. K_p,brain ratio was determined as (K_p,brain in Mdr1a/1b-KO mice)/(K_p,brain in WT or hMDR1-MAC mice).

Substrate	WT	Mdr1a/1b-KO	hMDR1-MAC
Indinavir
AUC_{plasma (0–2 hour)}	188	141	224
AUC_{brain (0–2 hour)}	10.6	287	16.4
K_p,brain	0.0562	2.03	0.0735
K_p,brain ratio	36.2		27.7
Loperamide
AUC_{plasma (0–2 hour)}	162	141	119
AUC_{brain (0–2 hour)}	17.2	708	64.0
K_p,brain	0.107	5.03	0.539
K_p,brain ratio	47.2		9.33
Paclitaxel
AUC_{plasma (0–2 hour)}	3660	1840	2330
AUC_{brain (0–2 hour)}	218	1110	210
K_p,brain	0.0594	0.603	0.0900
K_p,brain ratio	10.2		6.70
Quinidine
AUC_{plasma (0–2 hour)}	307	258	223
AUC_{brain (0–2 hour)}	346	3610	555
K_p,brain	1.13	14.0	2.49
K_p,brain ratio	12.4		5.63
Ritonavir
AUC_{plasma (0–2 hour)}	2860	1860	1840
AUC_{brain (0–2 hour)}	49.7	740	112
K_p,brain	0.0174	0.397	0.0608
K_p,brain ratio	22.9		6.53
Verapamil
AUC_{plasma (0–2 hour)}	206	169	199
AUC_{brain (0–2 hour)}	64.9	876	167
K_p,brain	0.315	5.17	0.838
K_p,brain ratio	16.4		6.16
Vinblastine
AUC_{plasma (0–2 hour)}	66.0	82.5	64.0
AUC_{brain (0–2 hour)}	79.2	727	126
K_p,brain	1.20	8.81	1.97
K_p,brain ratio	7.34		4.47