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

Abstract

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 ICratios COX-1:COX-2, 129:1 in dogs, 32:1 in cats). At registered dosages (2&#xa0;mg/kg subcutaneously in dogs and cats, 1-4&#xa0;mg/kg orally in dogs and 1-2.4&#xa0;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&#xa0;ml/kg in dogs and 190&#xa0;ml/kg in cats). In consequence, the terminal half-life in blood (<2&#xa0;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&#xa0;month), eight-fold (cat, 6&#xa0;weeks) and five-fold (dog, 6&#xa0;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.