Table 2. In vivo and in vitro pharmacokinetic (PK) parameters for E209 as predicted using compartmental PK analysis in male Beagle dogs, female Swiss outbred mice and the male Sprague–Dawley rat following IV and oral administration.

	Rat (mean)	Mouse (mean)	Dog* (mean)	Human (mean)
In vivo PK parameters
IV dose (mg kg−1)	2	2	1	N/A
PO dose (mg kg−1)	9	10	5	15mg†
Central clearance, CL (l h−1 kg−1)	1.6	4.3	1.1	0.41
Central volume of distribution Vc (l kg−1)	0.54	0.99	0.76	0.54†
Inter-compartmental clearance 1, Q1 (l −1 h−1 kg−1)	1.76	10.3	2.8	0.45†
Inter-compartmental clearance 2, Q2 (l h−1 kg−1)	0.08	0.97	0.13	0.020
Peripheral Volume of distribution 1, Vp1 (l kg−1)	2.1	1.49	0.37	2.1†
Peripheral volume of distribution 2, Vp2 (l kg−1)	2.0	10.8	2.95	2.0†
Absorption rate constant Ka (h−1)	0.31	0.79	0.33	0.31†
F (%)	62	82	40	62†
In vitro microsomal data
Degradation half-life (min)	48	132	173	68
In vitro CLint (μl min−1 mg−1 protein)	36	13	10	25
Microsome-predicted EH	0.48	0.22	0.38	0.50

^*Supplementary Methods and Supplementary Table 9 in Supporting Information.

^†On the basis of allometric scaling from rat parameters.