While the random hold-out test set provides an impression of the model performance, the results depend on the initial random seed. A bootstrap analysis was performed to analyze the model performance more extensively, where the dataset was split randomly fifty times (80%/20%). The mean bootstrapping R 2 for A 2A R pKi is 0.70 (range 0.66-0.74) and the RMSE is 0.63 (range 0.58-0.68) (Figure ). The bootstrapping results affirm that the model for CL (R 2 0.34 (0.26-0.43)) performs worse than the models for the other PK properties FU (R 2 0.64 (range 0.57-0.72)) and VDSS (0.50 (range 0.42-0.57)).