Table 2.

In vitro metabolism of fluralaner and afoxolaner

Human hepatocytesDog hepatocytesRat hepatocytesHuman plasma, unbound fraction (%)
Compoundt1/2, minCLint, μL/min/ 106 cellst1/2, minCLint, μL/min/ 106 cellst1/2, minCLint, μL/min/ 106 cells
Fluralaner>216.8<6.4>216.8<6.4>216.8<6.41.6
Afoxolaner>216.8<6.4>216.8<6.4>216.8<6.4ND
7-Ethoxy-coumarin20.169.114.099.361.822.4
  • The table shows in vitro degradation of fluralaner and afoxolaner and, as a control, ethoxycoumarin, by human, dog and rat primary hepatocytes. The results are shown as the half-life (t1/2) and intrinsic in vitro clearance (CLint) of each compound. The data are based on 5-point time courses. The last column shows the percentage of afoxolaner and fluralaner unbound to human plasma. The results are based on 3 replicate experiments. ND, not detected; no peak was observed in the buffer sample, indicating that the molecule may be highly bound to plasma proteins.