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

J Vet Pharmacol Ther. 2022 Jul;45(4):325-351. doi: 10.1111/jvp.13052. Epub 2022 Apr 22.

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 IC50 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.

Keywords: NSAID; cat; coxib; dog; robenacoxib.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Cat Diseases* / chemically induced
  • Cat Diseases* / drug therapy
  • Cats
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Diphenylamine / analogs & derivatives
  • Diphenylamine / pharmacology
  • Diphenylamine / therapeutic use
  • Dog Diseases* / drug therapy
  • Dogs
  • Phenylacetates / pharmacology
  • Phenylacetates / therapeutic use

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Phenylacetates
  • Diphenylamine
  • Cyclooxygenase 2
  • robenacoxib