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American journal of veterinary research2008; 69(11); 1399-1405; doi: 10.2460/ajvr.69.11.1399

Pharmacokinetics of firocoxib after administration of multiple consecutive daily doses to horses.

Abstract: To determine pharmacokinetic parameters and variables, firocoxib concentrations in urine and plasma, urine-to-plasma ratios, and the urine depletion profile of firocoxib and to evaluate whether the pharmacokinetic behavior of firocoxib was governed by linear processes after multiple doses of firocoxib were administered IV and orally. Methods: 6 healthy female horses (5 Paint horses and 1 Quarter Horse) in experiment 1 and 12 healthy male and female horses in experiment 2. Methods: In experiment 1, 6 horses were orally administered firocoxib paste once daily for 12 consecutive days, and plasma and urine samples were obtained and analyzed. In a second experiment, 12 horses received IV injections of firocoxib solution once daily for 9 consecutive days, and plasma was obtained and analyzed. Results: Mean +/- SD clearance and steady-state volume of distribution of firocoxib were 40.5 +/- 14.7 mL/h/kg and 2.3 +/- 0.7 L/kg, respectively. Mean half-life was 44.2 +/- 21.6 hours and 36.5 +/- 9.5 hours for IV and oral administration, respectively. The urine concentration- time curve decreased in parallel with the plasma concentration-verus-time curve. Renal clearance (0.26 +/- 0.09 mL/kg/h) was low, compared with total body clearance, which indicated that the main route of elimination was hepatic clearance. Conclusions: The pharmacokinetics of firocoxib during prolonged use were determined. Use of plasma or urine to ascertain drug concentrations in horses is scientifically valid because the plasma-to-urine ratio was consistent over time and among horses.
Publication Date: 2008-11-05 PubMed ID: 18980421DOI: 10.2460/ajvr.69.11.1399Google Scholar: Lookup
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  • Comparative Study
  • Journal Article

Summary

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The research article investigates the behavior of firocoxib, a non-steroidal anti-inflammatory drug, in a horse’s body after multiple doses, through both oral and intravenous administration, by analyzing firocoxib concentrations in urine and plasma.

Research Methodology

The research was conducted in two separate experiments:

  • In the first experiment, six healthy female horses, which included five Paint horses and one Quarter Horse, were administered firocoxib orally in the form of a paste for twelve consecutive days. Both urine and plasma samples were collected for analysis.
  • In the second experiment, twelve healthy male and female horses were administered intravenous injections of firocoxib for nine consecutive days. In this case, only plasma samples were collected and analysed.

Research Findings

Through an analysis of the collected samples, researchers were able to determine the following:

  • The mean clearance and steady-state volume of distribution of firocoxib in the body were determined to be 40.5 mL/h/kg and 2.3 L/kg respectively. These values indicate the rate at which the drug is cleared from the bloodstream and the theoretical volume that would be necessary to contain the total amount of the administered drug at the same concentration that it is present in the blood plasma.
  • The mean half-life of the drug was calculated to be around 44.2 hours for intravenous administration and 36.5 hours for oral administration. The half-life of a drug is the period of time required for the concentration or amount of drug in the body to be reduced by one-half.
  • The concentration of firocoxib in the urine decreased in parallel with its concentration in the plasma.
  • The renal clearance was found to be low (0.26 mL/kg/h) compared to the total body clearance, indicating that the main route of elimination of the drug is through the liver (hepatic clearance), not the kidneys.

Research Conclusions

The researchers concluded that:

  • The pharmacokinetics, or how the drug moves through the horse’s body over time, of firocoxib during prolonged use were determined.
  • It is possible to use blood plasma or urine to determine drug concentrations in horses. This is because the ratio of drug concentration in plasma to that in urine remained consistent over the time and among different horses.

In essence, this research provides valuable information about how the drug firocoxib behaves in the body of horses over time after multiple doses. It presents a reference for how one might monitor this drug’s concentration in a horse’s body using blood plasma or urine samples.

Cite This Article

APA
Letendre LT, Tessman RK, McClure SR, Kvaternick VJ, Fischer JB, Hanson PD. (2008). Pharmacokinetics of firocoxib after administration of multiple consecutive daily doses to horses. Am J Vet Res, 69(11), 1399-1405. https://doi.org/10.2460/ajvr.69.11.1399

Publication

ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 69
Issue: 11
Pages: 1399-1405

Researcher Affiliations

Letendre, Laura T
  • Merial Ltd, 3239 Satellite Blvd, Duluth, GA 30096, USA.
Tessman, Ronald K
    McClure, Scott R
      Kvaternick, Valerie J
        Fischer, James B
          Hanson, Peter D

            MeSH Terms

            • 4-Butyrolactone / administration & dosage
            • 4-Butyrolactone / analogs & derivatives
            • 4-Butyrolactone / blood
            • 4-Butyrolactone / pharmacokinetics
            • 4-Butyrolactone / urine
            • Administration, Oral
            • Animals
            • Chromatography, Liquid / veterinary
            • Dose-Response Relationship, Drug
            • Female
            • Horses
            • Injections, Intravenous / veterinary
            • Male
            • Sulfones / administration & dosage
            • Sulfones / blood
            • Sulfones / pharmacokinetics
            • Sulfones / urine
            • Tandem Mass Spectrometry / veterinary

            Citations

            This article has been cited 9 times.
            1. Mercer MA, Davis JL, McKenzie HC. The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses. Animals (Basel) 2023 May 10;13(10).
              doi: 10.3390/ani13101597pubmed: 37238029google scholar: lookup
            2. Fadel C, Giorgi M. Synopsis of the pharmacokinetics, pharmacodynamics, applications, and safety of firocoxib in horses. Vet Anim Sci 2023 Mar;19:100286.
              doi: 10.1016/j.vas.2023.100286pubmed: 36684818google scholar: lookup
            3. Jacobs CC, Schnabel LV, McIlwraith CW, Blikslager AT. Non-steroidal anti-inflammatory drugs in equine orthopaedics. Equine Vet J 2022 Jan 25;54(4):636-48.
              doi: 10.1111/evj.13561pubmed: 35076950google scholar: lookup
            4. Bennett TE, Pavek TJ, Schwark WS, Singh B. Comparison of Nociceptive Effects of Buprenorphine, Firocoxib, and Meloxicam in a Plantar Incision Model in Sprague-Dawley Rats. J Am Assoc Lab Anim Sci 2021 Sep 1;60(5):539-548.
            5. Donnell JR, Frisbie DD. Use of firocoxib for the treatment of equine osteoarthritis. Vet Med (Auckl) 2014;5:159-168.
              doi: 10.2147/VMRR.S70207pubmed: 32670856google scholar: lookup
            6. Barton MH, Darden JE, Clifton S, Vandenplas M. Effect of firocoxib on cyclooxygenase 2, microsomal prostaglandin E2 synthase 1, and cytosolic phospholipase A2 gene expression in equine mononuclear cells. Am J Vet Res 2015 Dec;76(12):1051-7.
              doi: 10.2460/ajvr.76.12.1051pubmed: 26618729google scholar: lookup
            7. Barton MH, Paske E, Norton N, King D, Giguère S, Budsberg S. Efficacy of cyclo-oxygenase inhibition by two commercially available firocoxib products in horses. Equine Vet J 2014 Jan;46(1):72-5.
              doi: 10.1111/evj.12095pubmed: 23662599google scholar: lookup
            8. Shapiro AJ, Kimble B, Hulst F, Herrin KV, Marschner C, Chen CJ, Govendir M. Pharmacokinetic profile of oral firocoxib in the koala (Phascolarctos cinereus). PLoS One 2025;20(9):e0332448.
              doi: 10.1371/journal.pone.0332448pubmed: 41026701google scholar: lookup
            9. Ignácio FS, Garcia LV, de Souza GG, Amatti LZ, de Barros LD, Bergfelt DR, Camargo GS, de Meira C, de Almeida BFM. Hematological and Biochemical Effects Associated with Prolonged Administration of the NSAID Firocoxib in Adult Healthy Horses. Vet Sci 2024 Jun 5;11(6).
              doi: 10.3390/vetsci11060256pubmed: 38922003google scholar: lookup