TABLE 2

Methods and statistics used to evaluate Korzekwa and Nagar’s model for predicting Vd

MethodTargetaabNR2AAFEAFEWithin 2-fold ErrorWithin 3-fold Error
%
GNE-liver microsomeAll species18.22 ± 1.391.76 ± 0.283370.4391.861.0665.086.0
KN-liver microsomebAll species20 ± 0.200.76 ± 0.433370.4461.891.1664.184.0
KN-liver microsomeHuman20 ± 0.200.76 ± 0.43600.7001.920.9865.081.7
KN-liver microsomeCyno20 ± 0.200.76 ± 0.43170.6861.610.7270.694.1
KN-liver microsomeDog20 ± 0.200.76 ± 0.43200.3421.720.8975.085.0
KN-liver microsomeMouse20 ± 0.200.76 ± 0.431100.3321.891.2262.782.7
KN-liver microsomeRat20 ± 0.200.76 ± 0.431300.3481.941.3462.384.6
KN-brainCDMR20 ± 0.200.76 ± 0.431050.5171.791.3469.585.7
KN-lungCDMR20 ± 0.200.76 ± 0.43140.1211.841.2657.185.7
KN-exp fumicCDMR20 ± 0.200.76 ± 0.431600.2911.961.2562.581.9
KN-calc fumicCDMR20 ± 0.200.76 ± 0.431600.1132.210.8851.975.0
  • a, first coefficient from Korzekwa and Nagar’s model; b, second coefficient from Korzekwa and Nagar’s model; calc fumic, calculated fraction unbound in microsome using physiochemical properties; CDMR, cyno, dog, mouse, and rat; exp fumic, experimentally measured fraction unbound in microsome; GNE, Genentech; KN, Korzekwa and Nagar.

  • a “All species” represents human, cyno, dog, mouse, and rat.

  • b KN coefficients applied to GNE data.