Table IV.

Predicted human PK properties supporting nomination of AZD1283 into clinical development versus select clinical oral PK parameters from 250 mg dose cohort

Parameter	AZD1283
Predicted human F a	76 to 100
Predicted human clearance (mL/min/kg)	0.4 to 3.3a
Predicted human V ss (L/kg)	0.3 to 1.1
Predicted human F oral (%)	65 to 100
Predicted biologically effective dose twice daily (mg/dose)	250
CL/F oral (L/h)	601b
Projected CL/F oral (mL/min/kg)	3.5c
V z/F oral (L)	1436b
Projected V z/F oral (L/kg)	0.5c
Oral half-life (hours)	1.65
Estimated F oral (%)	<5d

^aAllometry performed using dog and monkey PK, mouse and rat excluded due to plasma stability issues with AZD1283. Separate allometric predictions were made from dog and monkey, respectively, factoring in correction for species differences in plasma protein binding

^bThe clearance and volume of distribution were reported as CL/F _oral and V _z/F _oral as they were derived from oral dosing

^cProjected CL/F _oral and V_z/F _oral with bioavailability estimate set at 2.5%

^dEstimated bioavailability at all clinical doses