• 1. Giraudel JM, King JN, Jeunesse EC, et al. Use of a pharmacokinetic/pharmacodynamic approach in the cat to determine a dosage regimen for the COX-2 selective drug robenacoxib. J Vet Pharmacol Ther 2009; 32: 1830.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. Giraudel JM, Gruet P, Alexander DG, et al. Evaluation of orally administered robenacoxib versus ketoprofen for treatment of acute pain and inflammation associated with musculoskeletal disorders in cats. Am J Vet Res 2010; 71: 710719.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Kamata M, King JN, Seewald W, et al. Comparison of injectable robenacoxib versus meloxicam for peri-operative use in cats: results of a randomised clinical trial. Vet J 2012; 193: 114118.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. King JN, Hotz R, Reagan EL, et al. Safety of oral robenacoxib in the cat. J Vet Pharmacol Ther 2012; 35: 290300.

  • 5. Pelligand L, King JN, Toutain PL, et al. Pharmacokinetic/pharmacodynamic modelling of robenacoxib in a feline tissue cage model of inflammation. J Vet Pharmacol Ther 2012; 35: 1932.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. US FDA. Guidance for industry: bioanalytical method validation. May 2001. Available at: www.fda.gov/downloads/Drugs/…/Guidances/ucm070107.pdf. Accessed Dec 19, 2011.

    • Search Google Scholar
    • Export Citation
  • 7. US FDA. Guidance for industry No. 35: bioequivalence guideline. Docket No. 94D-0401. Nov 2006. Available at: www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/ucm052363.pdf. Accessed Dec 19, 2011.

    • Search Google Scholar
    • Export Citation
  • 8. The European Agency for the Evaluation of Medicinal Products. Evaluation of medicines for veterinary use. Guidelines for the conduct of pharmacokinetic studies in target animal species. EMEA/CVMP/133/99-FINAL. 2000. Available at: www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/10/WC500004355.pdf. Accessed Dec 19, 2011.

    • Search Google Scholar
    • Export Citation
  • 9. Jung M, Lees P, Seewald W, et al. Analytical determination and pharmacokinetics of robenacoxib in the dog. J Vet Pharmacol Ther 2009; 32: 4148.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Toutain PL, Bousquet-Mélou A. Plasma clearance. J Vet Pharmacol Ther 2004; 27: 415425.

  • 11. Giraudel JM, Toutain PL, King JN, et al. Differential inhibition of cyclooxygenase isoenzymes in the cat by the NSAID robenacoxib. J Vet Pharmacol Ther 2009; 32: 3140.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12. Lascelles BDX, Court MH, Hardie EM, et al. Nonsteroidal anti-inflammatory drugs in cats: a review. Vet Anaesth Analg 2007; 34: 228250.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13. Toutain PL, Bousquet-Mélou A. Volumes of distribution. J Vet Pharmacol Ther 2004; 27: 441453.

  • 14. German AJ, Cannon MJ, Dye C, et al. Oesophageal strictures in cats associated with doxycycline therapy. J Feline Med Surg 2005; 7: 3341.

  • 15. Frowde PE, Battersby IA, Whitley NT, et al. Oesophageal disease in 33 cats. J Feline Med Surg 2011; 13: 564569.

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Effects of route of administration and feeding schedule on pharmacokinetics of robenacoxib in cats

Jonathan N. King BVSc, PhD1, Martin Jung Dr rer nat2, Max P. Maurer PhD3, Vincent B. Schmid DVM4, Wolfgang Seewald PhD5, and Peter Lees PhD, DSc6
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  • 1 Clinical Development, Novartis Animal Health Inc, Schwarzwaldallee 215, CH-4058, Basel, Switzerland.
  • | 2 Centre de Recherche Sante Animale SA, Novartis Animal Health Inc, CH-1566, St Aubin, Switzerland.
  • | 3 Centre de Recherche Sante Animale SA, Novartis Animal Health Inc, CH-1566, St Aubin, Switzerland.
  • | 4 Centre de Recherche Sante Animale SA, Novartis Animal Health Inc, CH-1566, St Aubin, Switzerland.
  • | 5 Clinical Development, Novartis Animal Health Inc, Schwarzwaldallee 215, CH-4058, Basel, Switzerland.
  • | 6 Department of Veterinary Basic Sciences, The Royal Veterinary College, University of London, Hatfield, Hertfordshire, AL9 7TA, England.

Abstract

Objective—To establish pharmacokinetics of robenacoxib after administration to cats via the IV, SC, and oral routes.

Animals—24 cats.

Procedures—In a crossover design, robenacoxib was administered IV, SC, and orally (experiment 1) and orally (experiment 2) to cats with different feeding regimens. Blood robenacoxib concentrations were assayed, with a lower limit of quantification of 3 ng/mL.

Results—In experiment 1, geometric mean pharmacokinetic values after IV administration of robenacoxib were as follows: blood clearance, 0.44 L/kg/h; plasma clearance, 0.29 L/kg/h; elimination half-life, 1.49 hours; and volume of distribution at steady state (determined from estimated plasma concentrations), 0.13 L/kg. Mean bioavailability was 69% and median time to maximum concentration (Cmax) was 1 hour for cats after SC administration of robenacoxib, whereas mean bioavailability was 49% and 10% and median time to Cmax was 1 hour and 30 minutes after oral administration to cats after food withholding and after cats were fed their entire ration, respectively. In experiment 2, geometric mean Cmax was 1,159, 1,201, and 692 ng/mL and area under the curve from 0 to infinity was 1,337, 1,383, and 1,069 ng × h/mL following oral administration to cats after food withholding, cats fed one-third of the daily ration, and cats fed the entire daily ration, respectively.

Conclusions and Clinical Relevance—For treatment of acute conditions in cats, it is recommended to administer robenacoxib by IV or SC injection, orally after food withholding, or orally with a small amount of food to obtain optimal bioavailability and Cmax.

Abstract

Objective—To establish pharmacokinetics of robenacoxib after administration to cats via the IV, SC, and oral routes.

Animals—24 cats.

Procedures—In a crossover design, robenacoxib was administered IV, SC, and orally (experiment 1) and orally (experiment 2) to cats with different feeding regimens. Blood robenacoxib concentrations were assayed, with a lower limit of quantification of 3 ng/mL.

Results—In experiment 1, geometric mean pharmacokinetic values after IV administration of robenacoxib were as follows: blood clearance, 0.44 L/kg/h; plasma clearance, 0.29 L/kg/h; elimination half-life, 1.49 hours; and volume of distribution at steady state (determined from estimated plasma concentrations), 0.13 L/kg. Mean bioavailability was 69% and median time to maximum concentration (Cmax) was 1 hour for cats after SC administration of robenacoxib, whereas mean bioavailability was 49% and 10% and median time to Cmax was 1 hour and 30 minutes after oral administration to cats after food withholding and after cats were fed their entire ration, respectively. In experiment 2, geometric mean Cmax was 1,159, 1,201, and 692 ng/mL and area under the curve from 0 to infinity was 1,337, 1,383, and 1,069 ng × h/mL following oral administration to cats after food withholding, cats fed one-third of the daily ration, and cats fed the entire daily ration, respectively.

Conclusions and Clinical Relevance—For treatment of acute conditions in cats, it is recommended to administer robenacoxib by IV or SC injection, orally after food withholding, or orally with a small amount of food to obtain optimal bioavailability and Cmax.

Contributor Notes

Supported by Novartis Animal Health Inc.

Dr. Lees served as a consultant in the past 5 years to Bayer Animal Health, Norbrook Laboratories, Novartis Animal Health Inc, Pfizer Animal Health Inc, and Vetoquinol.

Address correspondence to Dr. King (jonathan.king@novartis.com).