TABLE 7.

The Kp and Kp_uu values predicted from the compartmental BBB model describing the brain and plasma concentration-time profile following either intravenous or oral administration of SAR405838

Route of Administration	Intravenous		Oral			Mdr1a/b−/− Bcrp1−/−
	Wild Type	Mdr1a/b−/− Bcrp1−/−	Wild Type	Bcrp1−/−	Mdr1a/b−/−
AUC0→∞, plasma	15,915	15,915	63,748	63,955	63,503	64,165
AUC0→∞, brain	404	11,462	1243	1859	71,308	68,317
Kppreda	0.025	0.72	0.019	0.029	1.12	1.06
DApredb	—	28	—	1.5	58	55
Clin	0.131	0.131	0.138	0.138	0.138	0.138
Clout	5.1	0.181	7.1	4.7	0.118	0.126
CLin/CLoutc	0.026	0.72	0.019	0.029	1.17	1.10
DApredd	—	28	—	1.5	60	56

^aKp_pred, the ratio of model predicted AUC_{0→∞, brain} to model predicted AUC_{0→∞, plasma}.

^bDA_pred (distribution advantage), the ratio of Kp_knockout to Kp_wild-type.

^cThe ratio of model predicted clearance into the brain to model predicted clearance out of the brain compartment.

^dDA_pred (distribution advantage), the ratio of brain clearance ratio in wild-type to brain clearance ratio in transgenic mice.