Pharmacology, safety, efficacy and clinical uses of the COX‐2 inhibitor robenacoxib

Robenacoxib is a veterinary‐approved non‐steroidal anti‐inflammatory drug (NSAID) of the coxib group. It possesses anti‐hyperalgesic, anti‐inflammatory and anti‐pyretic properties. Robenacoxib inhibits the cyclooxygenase (COX)‐2 isoform of COX selectively (in vitro IC(50) ratios COX‐1:COX‐2, 129:1 in dogs, 32:1 in cats). At registered dosages (2 mg/kg subcutaneously in dogs and cats, 1–4 mg/kg orally in dogs and 1–2.4 mg/kg orally in cats), robenacoxib produces significant inhibition of COX‐2 whilst sparing COX‐1. The pharmacokinetic (PK) profile of robenacoxib is characterized by a high degree of binding to plasma proteins (>98%) and moderate volume of distribution (at steady state, 240 ml/kg in dogs and 190 ml/kg in cats). In consequence, the terminal half‐life in blood (<2 h) is short, despite moderate body clearance (0.81 L/kg/h) in dogs and low clearance (0.44 L/kg/h) in cats. Excretion is principally in the bile (65% in dogs and 72% in cats). Robenacoxib concentrates in inflamed tissues, and clinical efficacy is achieved with once‐daily dosing, despite the short blood terminal half‐life. In dogs, no relevant breed differences in robenacoxib PK have been detected. Robenacoxib has a wide safety margin; in healthy laboratory animals daily oral doses 20‐fold (dog, 1 month), eight‐fold (cat, 6 weeks) and five‐fold (dog, 6 months) higher than recommended clinical doses were well tolerated. Clinical efficacy and safety have been demonstrated in orthopaedic and soft tissue surgery, and in musculoskeletal disorders in dogs and cats.