TABLE 8

Summary comparison of accuracy of drug interactions prediction methods using various values for [I]in vivo



[I]in vivo

[I] = Csys
[I] = fu × Csys
[I] = Chep,inlet(est)
[I] = fu × Chep,inlet(est)
CYP1A2, CYP2C9, CYP2C19, and CYP2D6
   Geometric mean-fold error (All DDI) 1.33 1.39 1.52 1.29
   Geometric mean-fold error (DDI ≥2× only) 1.90 2.28 1.75 1.70
   RMSE (All DDI) 1.48 1.70 3.47 1.22
   RMSE (DDI ≥2× only) 3.13 3.69 7.18 2.62
   Identification of true positives (DDI ≥2×) 9 of 14 6 of 14 11 of 14 9 of 14
   Identification of true negatives (DDI <2×) 53 of 54 54 of 54 39 of 54 51 of 54
   Overall success rate (%)a 91 88 74 88
CYP3A
   Geometric mean-fold error (All DDI) 1.44 1.54 1.67 1.44
   Geometric mean-fold error (DDI ≥2× only) 1.91 2.25 2.36 1.87
   RMSE (All DDI) 7.25 3.21 9.57 2.57
   RMSE (DDI ≥ 2X only) 11.74 5.18 15.16 4.13
   Identification of true positives (DDI ≥2×) 12 of 16 9 of 16 14 of 16 11 of 16
   Identification of true negatives (DDI <2×) 26 of 26 26 of 26 23 of 26 25 of 26
   Overall success rate (%)a 90 83 88 86
All P450s
   Geometric mean-fold error (All DDI) 1.37 1.44 1.58 1.35
   Geometric mean-fold error (DDI ≥2× only) 1.90 2.26 2.05 1.79
   RMSE (All DDI) 4.63 2.39 6.51 1.86
   RMSE (DDI ≥2× only)
8.83
4.55
12.11
3.51
  • a The term “Overall Success Rate” refers to the percentage of times that predictions of drug interactions from in vitro data are properly categorized as greater than or <2-fold