TABLE 1

K_p,uu values of test compounds in cynomolgus monkeys

The K_{p,uu,lumbar CSF} values were compared with K_{p,uu,cisternal CSF} and K_p,uu,ISF values that were previously determined.

Test Compounds	In Vitro P-gp CER	AUC (ng∙h/ml)^{^a}		K_{p,uu,lumbar CSF}^{^a}	K_{p,uu,cisternal CSF}^{^b}^,^{^c}	K_p,uu,ISF^{^b}^,^{^d}	K_p,uu Ratio
Test Compounds	In Vitro P-gp CER	Unbound Plasma	Lumbar CSF	K_{p,uu,lumbar CSF}^{^a}	K_{p,uu,cisternal CSF}^{^b}^,^{^c}	K_p,uu,ISF^{^b}^,^{^d}
Antipyrine	1.0^{^b}	1730 ± 699	1840 ± 692	1.10 ± 0.15	1.05	0.857	1.1	1.3	1.2
Carbamazepine	1.0^{^b}	1170 ± 476	1560 ± 606	1.34 ± 0.10	1.19	1.27	1.2	1.1	0.94
Lamotrigine	1.1^{^b}	15,990 ± 1600	15,700 ± 943	0.990 ± 0.066	0.875	0.678	1.1	1.5	1.3
Ondansetron	2.0^{^b}	665 ± 118	570 ± 80	0.885 ± 0.259	0.481	0.483	1.8	1.8	1.0
E2074	2.2^{^b}	244 ± 38	255 ± 41	1.05 ± 0.11	0.733	0.480	1.4	2.2	1.5
Risperidone	3.9^{^b}	14.3 ± 3.7	6.59 ± 2.25	0.458 ± 0.074	0.133	0.126	3.4	3.6	1.1
Verapamil	5.4^{^b}	306 ± 21	124 ± 14	0.406 ± 0.058	0.183	0.0789	2.2	5.1	2.3
Paliperidone	8.9^{^e}	356 ± 166	73.7 ± 15.1	0.226 ± 0.061	0.0490	NT	4.6	NA	NA
Desloratadine	12^{^b}	409 ± 3	79.7 ± 2.9	0.195 ± 0.006	0.129	0.0609	1.5	3.2	2.1
Quinidine	13^{^b}	473 ± 66	132 ± 28	0.278 ± 0.029	0.169	0.0658	1.6	4.2	2.6

NA, not applicable; NT, not tested.
↵^a Mean ± S.D. of three animals.
↵^b Nagaya et al., 2014.
↵^c K_{p,uu,cisternal CSF} was the cisternal CSF-to-unbound plasma drug conc. ratio determined at steady state after intravenous infusion in cynomolgus monkeys.
↵^d K_p,uu,ISF was the ISF-to-unbound plasma drug conc. ratio determined at steady state after intravenous infusion in cynomolgus monkeys.
↵^e Mean of triplicate determinations.