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Equine veterinary journal2020; 52(5); 725-732; doi: 10.1111/evj.13244

Pharmacokinetics and pharmacodynamics of clodronate disodium evaluated in plasma, synovial fluid and urine.

Abstract: Clodronate is a non-nitrogenated bisphosphonate approved for use in horses. There are no peer-reviewed published reports describing the pharmacokinetics or evaluating renal health indices and urinary excretion patterns in conjunction with plasma and synovial fluid concentration following the systemic administration of clodronate to horses. Objective: Describe clodronate concentrations in plasma, urine and synovial fluid and evaluate the effects on renal indices after intramuscular administration to healthy horses. Methods: Experimental study with repeated measures. Methods: Six healthy adult horses received a single intramuscular dose of clodronate (1.8 mg/kg). Blood, synovial fluid and urine were collected prior to and after administration of clodronate up to 72, 48 and 168 hours respectively. Drug concentrations were measured using LC-MS/MS and noncompartmental pharmacokinetic analysis was performed. Renal function indices were also evaluated. Results: Clodronate was quantifiable for up to 24 hours in plasma and 48 hours in synovial fluid and detected at all time points in urine. Maximum plasma concentration of clodronate 210 ± 68.2 ng/mL occurred at approximately 34.8 ± 0.2 minutes after administration, while peak synovial concentration (57.7 ± 32.8 ng/mL) occurred at 2.67 ± 2.32 hours after administration and peak urine concentration (88 358.2 ± 79 521.4 ng/mL) occurred at 2.67 ± 2.58 hours post administration. Terminal half-life in plasma was 3.32 ± 1.25 and was 4.8 ± 3.05 hours in synovial fluid. Creatinine concentrations rose significantly after treatment but remained within normal adult reference ranges at all times. Conclusions: Limited number of animals and sampling times and the absence of urine collection for determination of concentration beyond 7 days. Conclusions: Clodronate is rapidly cleared from the blood and synovial fluid. It has variable and biphasic urinary excretion. While significant increase in blood creatinine concentrations was present after a single intramuscular dose of clodronate, values were never above the normal reference range. Further studies are warranted in horses undergoing exercise and those undergoing multiple dosing schemes.
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Publication Date: 2020-02-21 PubMed ID: 32003488DOI: 10.1111/evj.13244Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates the pharmacokinetics and pharmacodynamics of clodronate, a drug used in horses. It tracks the drug concentration in the horse’s plasma, urine, and synovial fluid after being administered intramuscularly, and it also evaluates the impact on renal health markers.

Objectives & Methodology

  • The goal of this research is to measure the levels of clodronate in the plasma, urine, and synovial fluid of horses after its administration. Moreover, it aims to assess the impact of the drug on the renal health of horses.
  • The researchers conducted an experimental study with repeated measures on six adult horses that received a single intramuscular dose of clodronate (1.8 mg/kg).
  • Samples of blood, synovial fluid, and urine were collected before and after administering the drug for 72, 48, and 168 hours respectively.
  • The concentrations of the drug in the collected samples were measured using Liquid Chromatography coupled with Tandem Mass Spectrometry (LC-MS/MS). Moreover, noncompartmental pharmacokinetic analysis was done, and renal function indices were also evaluated.

Results

  • Clodronate was detectable up to 24 hours in plasma and 48 hours in synovial fluid, and it was found in all urine samples collected at different time points.
  • The peak plasma, synovial, and urine concentration of clodronate were recorded approximately 34.8 minutes, 2.67 hours, and 2.67 hours after administration, respectively.
  • The drug’s half-life was found to be 3.32 hours in plasma and 4.8 hours in synovial fluid.
  • Significant increases in creatinine concentrations, a marker for renal health, were observed after treatment, but the values were still within the normal reference range for adult horses.

Conclusions

  • The study highlighted a few limitations like a small number of horses, limited collection times, and no urine collection for concentration measurement beyond seven days.
  • Despite those limitations, the study concluded that clodronate is rapidly cleared from the blood and synovial fluid of horses and is excreted from the urine in a variable and biphasic manner.
  • Even though there was a significant increase in blood creatinine concentrations, a marker for kidney function, the values were still within the normal range, indicating that the drug might not harm renal health. However, the scientists suggest that further studies should be done in horses subjected to exercise and those receiving multiple doses of the drug.

Cite This Article

APA
Krueger CR, Mitchell CF, Leise BS, Knych HK. (2020). Pharmacokinetics and pharmacodynamics of clodronate disodium evaluated in plasma, synovial fluid and urine. Equine Vet J, 52(5), 725-732. https://doi.org/10.1111/evj.13244

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 52
Issue: 5
Pages: 725-732

Researcher Affiliations

Krueger, Clarisa R
  • Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Mitchell, Colin F
  • Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Leise, Britta S
  • Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Knych, Heather K
  • K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.

MeSH Terms

  • Animals
  • Chromatography, Liquid / veterinary
  • Clodronic Acid
  • Horses
  • Plasma
  • Synovial Fluid
  • Tandem Mass Spectrometry / veterinary

Grant Funding

  • Louisiana State University Equine Health Studies Program

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Citations

This article has been cited 6 times.
  1. Vergara-Hernandez FB, Nielsen BD, Colbath AC. Is the Use of Bisphosphonates Putting Horses at Risk? An Osteoclast Perspective. Animals (Basel) 2022 Jul 3;12(13).
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  2. Totten KMC, Cunningham SA, Gades NM, Etzioni A, Patel R. Pharmacokinetic Assessment of Staphylococcal Phage K Following Parenteral and Intra-articular Administration in Rabbits. Front Pharmacol 2022;13:840165.
    doi: 10.3389/fphar.2022.840165pubmed: 35668926google scholar: lookup
  3. Knych HK, Janes J, Kennedy L, McKemie DS, Arthur RM, Samol MA, Uzal FA, Scollay M. Detection and residence time of bisphosphonates in bone of horses. J Vet Diagn Invest 2022 Jan;34(1):23-27.
    doi: 10.1177/10406387211050049pubmed: 34918585google scholar: lookup
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