TABLE 7

The Kp,pred and Kp,uu,pred values and the DA,pred values, using the pharmacokinetic parameters obtained from the compartmental BBB model describing the brain and plasma concentration-time profiles after administration of a single intravenous bolus (3 mg/kg, i.v.; N = 3 to 4 at each time point) or oral dose (30 mg/kg, PO; N = 4 at each time point) in FVB wild-type, Bcrp1(−/−), Mdr1a/b(−/−), and/or Mdr1a/b(−/−)Bcrp1(−/−) mice

The parameters are presented as the mean estimate.

Route of Administration	Genotype	Parameters
		AUC_{(0→∞),predicted} (Mean Estimate) h*μg/ml				Transient Steady State (Mean Estimate) μg/ml				Clearance Based (Mean Estimate)
		AUC_{(0→∞),plasma}	AUC_{(0→∞),brain}	Kp,pred^{^a}	DA,pred^{^b}	C_p,tss(µg/ml)	C_{max, brain}	Kp,pred^{^a}	DA,pred^{^b}	Kp,pred^{^a}	Kp,uu,pred^{^c}	DA,pred^{^b}
Intravenous	WT	4.0	3.6	0.89		1.2	1.1	0.89		0.89	0.11
	TKO	4.0	43.1	10.7	12	0.5	5.3	10.8	12.0	10.7	1.4	12.1
By mouth	WT	10.9	8.2	0.76		1.2	0.95	0.76		0.76	0.097
	Bcrp-KO	10.6	12.2	1.1	1.5	1.1	1.2	1.1	1.5	1.1	0.15	1.5
	Pgp-KO	11.2	35.9	3.2	4.2	1.1	3.4	3.2	4.2	3.2	0.41	4.2
	TKO	10.7	152.3	14.3	18.8	1.0	12.9	13.4	17.7	14.4	1.9	19.1

Bcrp-KO, Bcrp1(−/−); KO, knockout; Pgp-KO, Mdr1a/b(−/−); TKO, Mdr1a/b(−/−)Bcrp1(−/−); WT, wild-type.
↵^a Kp,pred, calculated by
↵^b DA,pred, calculated by Kp,pred,knockout/Kp,pred,wild-type, or Kp,uu,pred,knockout/Kp,uu,pred,wild-type.
↵^c Kp,uu,pred, calculated by .