Table 2. Permeability, Plasma and Brain Fraction Unbound, Brain Exposure, and PK Data^a.

	Caco-2 Papp (nm/sec)
Cpd	AB	BA	ER	species	plasma fu	brain fu	Cplasma,u (nM)	Cbrain,u (nM)	(B/P)u	iv ClT (min/mL/kg)	iv Vss (L/kg)	iv T1/2 (min)	%F
2b	339	224	0.7	rat	0.055	0.028	54.4	7.79	0.14	7.4	1.4	126	119
2c	−	−	−	monkey	0.043	−	17.9	−	−	16.5	1.52	210	12
3b	487	465	1.0	rat	0.639	0.525	1507	343	0.23	1.5	0.60	279	62.5
3c	−	−	−	monkey	0.532	−	5040	−	−	3.17	1.15	324	107
8d	360	221	0.6	rat	0.065	0.031	58.6	39.3	0.67	7.3	2.8	267	−
12d	477	528	1.1	rat	0.674	0.436	1767	212	0.12	1.94	0.65	239	126
15d	467	345	0.7	rat	0.408	−	−	−	−	2.2	0.91	294	73.6
16d	419	368	0.9	rat	0.291	0.109	348.0	85.4	0.25	1.07	2.25	1479	98.2
17d	437	519	1.2	rat	0.592	0.604	406.7	68.6	0.17	13.7	0.68	35	55
18d	91	345	3.8	rat	0.662	0.995	897.4	45.6	0.05	5.07	1.59	215	46.6

^aPK doses: iv, 1 mg/kg (rat), 10 mg/kg (monkey); oral, 3 mg/kg (rat), 5 mg/kg (monkey). Brain exposure dose: 1 mg/kg. Mean values for N = 3–4 rats, or 4 monkeys, per group. All rat data at 60 min: (B/P)_u = C_brain,u/C_plasma, u with C_brain,u = C_{brain, total} × bf_u and C_plasma,u = C_plasma,total × f_u. Monkey C_plasma,u data at 90 min (oral).

^bPK formulation: HPβCD.

^cPK formulation: iv HPβCD; oral 0.5% MC/water.

^dPK formulation: 1% DMSO, HPβCD in 0.9% NaCl.