Prediction of flunixin tissue residue concentrations in livers from diseased cattle

•Changes in pharmacokinetic parameters associated with diseased animals affect liver residue of flunixin in cattle.•Decreased clearance due to impaired liver or kidney function, or biliary excretion may cause violative flunixin residue.•Altered distribution due to body fluid shifts or decreased plasma protein binding may cause violative flunixin residue. Flunixin, a widely used non-steroidal anti-inflammatory drug, was a leading cause of violative residues in cattle. The objective of this analysis was to explore how the changes in pharmacokinetic (PK) parameters that may be associated with diseased animals affect the predicted liver residue of flunixin in cattle. Monte Carlo simulations for liver residues of flunixin were performed using the PK model structure and relevant PK parameter estimates from a previously published population PK model for flunixin in cattle. The magnitude of a change in the PK parameter value that resulted in a violative residue issue in more than one percent of a cattle population was compared. In this regard, elimination clearance and volume of distribution affected withdrawal times. Pathophysiological factors that can change these parameters may contribute to the occurrence of violative residues of flunixin.