Table 9.

In Vivo DMPK Profiling of Select 5-Chloropyridin-2-yl Ether Analogues

			rat IV PK resultsb			rat IP tissue distribution resultsc,d,e
no.	rat plasma Fua	rat brain Fua	t1/2 (min)	CLplasma (mL/min/kg)	VSS (L/kg)	plasma conc (μM)	brain conc (μM)	K p f	K p,uu g
99	0.045	0.032	194	13	2.2	1.68	2.41	1.4	1.0
101	0.118		21	50	1.2
106	0.083	0.052	42	37	1.6	9.49	15.85	1.7	1.0
108	0.092		30	50	1.9
109	0.078	0.033	59	22	1.4	4.52	5.28	1.2	0.49

^aF_u = fraction unbound.

^bn = 2; dose = 0.2 mg/kg; solution in 10% EtOH, 38–40% PEG 400, 50–52% DMSO (2 mg/mL).

^cn = 2; time point = 15 min; dose = 10 mg/kg.

^dFor 99 and 109, fine homogeneous suspension in 0.1% Tween 80 and 0.5% methyl cellulose in H₂O (4 mg/mL).

^eFor 106, fine homogeneous suspension in 10% EtOH and 90% PEG400 (4 mg/mL).

^fK_p = total brain to total plasma ratio.

^gK_p,uu = unbound brain (brain F_u × total brain) to unbound plasma (plasma F_u × total plasma) ratio