[Jane L]

This is clearly explained in Dogs Monthly magazine April issue. Part explained the numerous seizures which are a listed possible reaction to the ingredient Fluralaner on the new topical though not added to the oral stil.

Regarding liver and kidneys it says :-

“Fluralaner will in fact pass through both the liver and the kidneys but is not metabolised by either and is excreted in the faeces in the same form. I concede that the drug is not metabolised by the liver and kidneys but this does not mean that the organs are not affected. The liver will try very hard to break down the foreign substance or toxin and in doing so damages its performance. The enzymes levels rise dramatically as it attempts unsuccessfully to destroy fluralaner. It would seem, as resilient as a liver can be, there are examples of the liver failing. Similarly with the kidneys, They do not metabolise fluralaner but this does not mean the kidneys do not try to rid the body of the nasty toxin which kills insects. As a result the kidneys are in some cases severely damaged and can fail. Some of the other symptoms reported could be because the drug is circulating in the body round and round trying to find a way out. Pancreatic metabolism could be affected as well. It is reported that the drug is only excreted in the stools. In order to get there, once absorbed into the blood stream, it can only go via the liver and the biliary system, so it’s not surprising it takes a long time to be eliminated.”

Also in this article it says the main route of elimination is likely to be hepatic.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886404/

“For fluralaner, the main route of elimination is likely hepatic because the high plasma protein binding [4] indicates minimal elimination via renal filtration. Plasma clearance can therefore be assumed to be equivalent to hepatic clearance. The clearance of fluralaner is low with only 0.14 L/kg/day in dogs [4] and 0.23 L/kg/day in cats. Considering a physiological hepatic blood flow of approximately 44.5 L/kg/day in the dog or 38.6 L/kg/day in the cat [15] and assuming hepatic clearance of fluralaner of 0.14 L/kg/day and 0.23 L/kg/day, respectively, the hepatic extraction ratio for fluralaner is estimated to be low (0.3 % in dogs [4] and 0.2 % in cats). The low clearance may be due to the high protein binding of fluralaner, which limits the unbound fraction of fluralaner in the vascular system that can be presented to clearing organs and/or due to a low intrinsic hepatic capacity to metabolize fluralaner [16–18].”