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American journal of veterinary research2023; 84(8); doi: 10.2460/ajvr.23.03.0051

Pharmacokinetics and plasma protein binding of a single dose of clodronate disodium are similar for juvenile sheep and horses.

Abstract: To determine the single-dose pharmacokinetics of clodronate disodium (CLO) in juvenile sheep and the plasma protein binding (PPB) of CLO in juvenile sheep and horses. Methods: 11 juvenile crossbred sheep (252 ± 6 days) for the pharmacokinetic study. Three juvenile crossbred sheep (281 ± 4 days) and 3 juvenile Quarter Horses (599 ± 25 days) for PPB analysis. Methods: CLO concentrations were determined using liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental analysis from plasma samples obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, and 72 hours after CLO administered IM at 0.6 mg/kg. PPB was determined using equine and ovine plasma in a single-use rapid equilibrium dialysis system. Results: The mean and range for maximum plasma concentration (Cmax: 5,596; 2,396-8,613 ng/mL), time of maximal concentration (Tmax: 0.5; 0.5-1.0 h), and area under the curve (AUCall: 12,831; 7,590-17,593 h X ng/mL) were similar to those previously reported in horses. PPB in sheep and horses was moderate to high, with unbound fractions of 26.1 ± 5.1% in sheep and 18.7 ± 7.5% in horses, showing less than a 1.4-fold difference. Conclusions: The pharmacokinetic parameters and PPB of CLO in juvenile sheep were similar to those previously reported in horses. The results suggest that juvenile sheep can be utilized as an animal model for studying the potential risks and/or benefits of bisphosphonate use in juvenile horses.
Publication Date: 2023-07-21 PubMed ID: 37460095DOI: 10.2460/ajvr.23.03.0051Google Scholar: Lookup
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  • Journal Article

Summary

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The study examines the pharmacokinetics, the study of how a drug moves within a body, of a single dose of clodronate disodium in young sheep, as well as how it binds with proteins in the plasma in both young sheep and horses.

Objective and Methodology of the Study

  • The goal was to understand how a single dose of clodronate disodium (also known as CLO), a medication often used to manage bone-related diseases, behaves in the body of young crossbred sheep.
  • Another aim was to study how this drug binds with proteins in the blood plasma (plasma protein binding or PPB) of both young sheep and horses.
  • For the study, a total of 14 sheep were monitored, alongside 3 young quarter horses for the PPB analysis.
  • They utilized liquid chromatography-mass spectrometry to determine CLO concentrations.
  • The pharmacokinetic parameters were calculated by examining plasma samples taken at intervals of up to 72 hours after administration of the medication.
  • PPB was checked using the plasma of horses and sheep in a rapid equilibrium dialysis system.

Results

  • The study found that key parameters such as maximum plasma concentration, time of maximal concentration, and area under the curve (AUC), were similar to values previously reported in horses.
  • PPB in sheep and horses was found to be moderate to high, with the unbound fraction being slightly higher in sheep than in horses. However, the difference was less than 1.4-fold.

Conclusion

  • The research concluded that the behavior and effects of CLO in young sheep were similar to those seen in horses.
  • This suggests that researchers could use juvenile sheep as an animal model to study risks and benefits of bisphosphonate use. This is particularly helpful for research related to how these drugs behave in young horses, potentially contributing to better veterinary care for these animals.

Cite This Article

APA
Vergara-Hernandez FB, Nielsen BD, Kottwitz JJ, Panek CL, Robison CI, Paris BL, Welsh TH, Bradbery AN, Leatherwood JL, Colbath AC. (2023). Pharmacokinetics and plasma protein binding of a single dose of clodronate disodium are similar for juvenile sheep and horses. Am J Vet Res, 84(8). https://doi.org/10.2460/ajvr.23.03.0051

Publication

ISSN: 1943-5681
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 84
Issue: 8

Researcher Affiliations

Vergara-Hernandez, Fernando B
  • Department of Animal Science, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI.
Nielsen, Brian D
  • Department of Animal Science, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI.
Kottwitz, Jack J
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI.
Panek, Char L
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY.
Robison, Cara I
  • Department of Animal Science, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI.
Paris, Brittany L
  • Department of Animal Science, College of Agriculture and Life Sciences, Texas A&M University, College Station, TX.
Welsh, Thomas H
  • Department of Animal Science, College of Agriculture and Life Sciences, Texas A&M University, College Station, TX.
Bradbery, Amanda N
  • Department of Animal and Range Sciences, College of Agriculture, Montana State University, Bozeman, MT.
Leatherwood, Jessica L
  • Department of Animal Science, College of Agriculture and Natural Resources, Tarleton State University, Stephenville, TX.
Colbath, Aimee C
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY.

MeSH Terms

  • Animals
  • Horses
  • Sheep
  • Clodronic Acid / pharmacology
  • Protein Binding
  • Chromatography, Liquid / veterinary
  • Area Under Curve
  • Administration, Oral
  • Half-Life

Citations

This article has been cited 1 times.
  1. Vergara-Hernandez FB, Nielsen BD, Popovich JM Jr, Panek CL, Logan AA, Robison CI, Ehrhardt RA, Johnson TN, Chargo NJ, Welsh TH Jr, Bradbery AN, Leatherwood JL, Colbath AC. Clodronate disodium does not produce measurable effects on bone metabolism in an exercising, juvenile, large animal model. PLoS One 2024;19(4):e0300360.
    doi: 10.1371/journal.pone.0300360pubmed: 38626145google scholar: lookup