A team of scientists at Tokyo University of Agriculture and Technology has described the pharmacokinetics of flunixin-meglumine (FNX) in the cat. Although it is used in the United States for only large animals, this NSAID is popular because it has strong analgesic properties. It has been studied in humans, rabbits, dogs, and cows. This study sought to determine the drug's half-life, mechanism of elimination, and whether it recycles in the feline enterohepatic circulation and is taken up by liver cells. Four healthy Abyssinian-mix cats participated in 3 sequential pharmacokinetic studies of FNX with a washout period of 4 weeks in between. In phase A, FNX (2 mg/kg) was given by injection. In phase B, FNX (2 mg/kg) was given by injection along with oral cholestyramine (ChSA) (1 g) to test for enterohepatic circulation of FNX (ChSA binds NSAIDs in the small intestine and expels them from the body). In phase C, FNX and pravastatin sodium were given by injection to test the active transport of FNX in feline liver cells. Results showed an elimination half-life of 6.6 hours (almost 3 times that of the only other study reported to date); high in vitro plasma protein binding (99%); and recovery in urine of only 0.4% of the dose, indicating that excretion does not occur just though urine. Estimated renal clearance closely corresponded to the renal plasma flow rate, indicating active renal tubular secretion. The pravastatin sodium phase indicated that liver cells take up FNX, although pravastatin may partially inhibit the inflow of FNX into the liver as it does in rabbits. The ChSA phase indicated that the drug undergoes enterohepatic circulation (ChSA may also interrupt enterohepatic circulation and help prevent gastrointestinal disorders in cats). It was concluded that at least 2 active transport mechanisms are involved in FNX pharmacokinetics in cats-sinusoidal uptake by liver cells and renal tubular secretion.
COMMENTARY: Probably one of the most-asked questions is how to manage chronic pain in cats. In dogs, the mainstay of chronic therapy is long-term and relatively safe NSAIDs. Not so with cats. Only a few studies have examined why and how cats metabolize NSAIDs. Although this study uses flunixin, a drug used only in large animals in the United States, it sheds light on some of the exact mechanisms by which cats handle this class of drug. This should open the door for more research and, it is hoped, ways to adapt existing drugs or develop new drugs for use in cats.
Pharmacokinetics of flunixin in the cat: enterohepatic circulation and active transport mechanism in the liver. Horii Y, Ikenaga M, Shimoda M, Kokue E. J VET PHARMACOL THER 27:65-69, 2004.