Population pharmacokinetic analysis of blood and joint synovial fluid concentrations of robenacoxib from healthy dogs and dogs with osteoarthritis.

PURPOSE: The purpose of this population analysis was to characterize the pharmacokinetic properties of robenacoxib in blood and stifle joint synovial fluid of dogs. METHODS: Data were obtained from two studies: 1) 8 healthy Beagle dogs in which an acute inflammation was induced by injection of urate crystals into one joint; 2) 95 dogs from various breeds diagnosed with osteoarthritis (OA). Robenacoxib concentrations in blood and synovial fluid were measured using a validated HPLC-UV and LC-MS method. Non-linear mixed effects modeling was performed using NONMEM6. RESULTS: A two-compartment pharmacokinetic model with linear elimination was developed to describe blood concentrations of robenacoxib. Blood clearance in healthy animals was found to be 75% higher than in OA dogs. Synovial fluid concentrations were modeled using an effect-compartment-type model predicting longer residence times in OA dogs compared to healthy Beagles (e.g. concentrations above the IC(50) for COX-2, respectively, 16 h vs. 10 h at 1.5 mg/kg). CONCLUSIONS: Robenacoxib was found to reside longer at the effect site (inflamed joint) compared to blood in both healthy and OA dogs. These results may explain the good efficacy observed with once-daily dosing in clinical trials and the high safety index of robenacoxib in dogs.

Clinical evaluation of meloxicam versus ketoprofen in cats suffering from painful acute locomotor disorders.

The aim of this study was to evaluate the efficacy and palatability of meloxicam 0.5mg/ml oral suspension, compared to ketoprofen tablets in cats suffering from painful acute locomotor disorders. This single blinded, positively-controlled, randomised, multicentre trial involved 121 client owned cats. Cats received either meloxicam (0.5mg/ml oral suspension) at 0.1mg/kg on day 1 followed by 0.05mg/kg q 24h on days 2-5, or ketoprofen 5mg tablets at 1.0mg/kg q 24h for 5 days. The efficacy of the two treatments was assessed subjectively by clinicians on day 6 using a clinical sum score (CSS). Palatability and accuracy of dosing were also assessed. The baseline CSS was not significantly different between the groups, and after 5 days of treatment the CSS had decreased to a similar extent, reflecting a reduction in pain. There were no significant differences between the CSS of each group at day 6. Both treatments were well tolerated. Meloxicam was significantly more palatable than ketoprofen, and allowed for more accurate dosing. Meloxicam and ketoprofen are a safe and efficacious treatment for acute locomotor disorders in cats. Meloxicam (Metacam) may be associated with superior compliance in clinical practice due to the higher palatability, which results in better ease of administration.