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Journal of veterinary pharmacology and therapeutics2008; 31(2); 108-116; doi: 10.1111/j.1365-2885.2007.00936.x

Comparative pharmacokinetics of two intravenous administration regimens of tiludronate in healthy adult horses and effects on the bone resorption marker CTX-1.

Abstract: Bioavailability and pharmacological effects of tiludronate were compared when administered as an intravenous (i.v.) bolus at a dosage of 0.1 mg/kg body weight (b.w.) once daily for 10 consecutive days (group 1, n = 6) and as a single constant rate infusion (CRI) at a total dose of 1 mg/kg b.w. (group 2, n = 6) in healthy adult horses. Tiludronate and carboxy-terminal cross-linking telopeptide of type I collagen (CTX-1) were measured in plasma and urine. There was no statistically significant difference in area under the curve (AUC) and clearance (Cl) between the two groups. Bioavailability of the CRI was 103% (not significantly different) that of the 10 daily i.v. bolus doses. Cumulative urine tiludronate excretion could not be compared between groups because of poor sensitivity of the assay in urine. Plasma and urine CTX-1 levels were not different between groups throughout the study. However, interindividual variations were greater in group 1 than in group 2. A significant decrease in CTX-1 levels was observed in plasma after the first administration in group 1, but not in urine; while in group 2, a significant decrease in CTX-1 concentrations was observed after treatment in both plasma and urine. In conclusion, both dosage regimens of tiludronate produced similar plasma exposure and pharmacological effects in adult healthy horses.
Publication Date: 2008-03-01 PubMed ID: 18307502DOI: 10.1111/j.1365-2885.2007.00936.xGoogle Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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 study compares the availability and effects of Tiludronate, a drug given to healthy horses, when administered in two different dosing methods. One group gets a regular dosage over 10 days, and the other gets a single dose. Both methods produced similar effects on the horse’s health.

Objective of the Study

The goal of the study was to compare:

  • The bioavailability,
  • The pharmacological effects of tiludronate,
  • The influence on the bone resorption marker CTX-1,

in two groups of healthy horses, each treated with a different regimen of intravenous tiludronate administration.

Research Design

A total of 12 healthy adult horses were divided into two groups, each treated with tiludronate differently:

  • Group 1 (6 horses) was administered a daily dosage of 0.1 mg/kg body weight of tiludronate through intravenous bolus for ten consecutive days,
  • Group 2 (6 horses) was treated with a single constant rate infusion of a total dose of 1 mg/kg body weight.

Measurements and Results

The researchers measured the concentration of tiludronate and CTX-1 (a bone resorption marker) in the plasma and urine of the horses. They found:

  • There was no statistically significant difference in the area under the curve (AUC) and clearance (Cl) between the two groups, which means both treatments produced a similar exposure of tiludronate in the bloodstream.
  • The bioavailability in Group 2 was 103% of Group 1, a result that was not considered statistically meaningful.
  • Urine tiludronate excretion could not be compared because the assay was not sensitive enough in urine.
  • There were no differences in plasma and urine CTX-1 levels between the two groups throughout the study, but there were more variations between individuals in Group 1 than in Group 2.
  • A significant decrease in plasma CTX-1 levels was observed after the first treatment application in Group 1, but not in the urine. In Group 2, however, a significant drop in plasma and urine CTX-1 levels was seen after administration.

Conclusion

Overall, both methods of administering tiludronate resulted in similar plasma exposure and pharmacological effects. The findings suggest both dosing regimens are effective for treating adult healthy horses with tiludronate.

Cite This Article

APA
Delguste C, Amory H, Guyonnet J, Thibaud D, Garnero P, Detilleux J, Lepage OM, Doucet M. (2008). Comparative pharmacokinetics of two intravenous administration regimens of tiludronate in healthy adult horses and effects on the bone resorption marker CTX-1. J Vet Pharmacol Ther, 31(2), 108-116. https://doi.org/10.1111/j.1365-2885.2007.00936.x

Publication

ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 31
Issue: 2
Pages: 108-116

Researcher Affiliations

Delguste, C
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liege, Liege, Belgium. cdelguste@ulg.ac.be
Amory, H
    Guyonnet, J
      Thibaud, D
        Garnero, P
          Detilleux, J
            Lepage, O M
              Doucet, M

                MeSH Terms

                • Animals
                • Area Under Curve
                • Bone Density Conservation Agents / administration & dosage
                • Bone Density Conservation Agents / pharmacokinetics
                • Bone Density Conservation Agents / pharmacology
                • Bone Remodeling / drug effects
                • Chemistry, Pharmaceutical
                • Collagen Type I / blood
                • Collagen Type I / drug effects
                • Collagen Type I / urine
                • Diphosphonates / administration & dosage
                • Diphosphonates / blood
                • Diphosphonates / pharmacokinetics
                • Diphosphonates / pharmacology
                • Female
                • Horses / metabolism
                • Infusions, Intravenous / veterinary
                • Injections, Intravenous / veterinary
                • Male

                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).
                  doi: 10.3390/ani12131722pubmed: 35804621google scholar: lookup
                2. Schubert DC, Neustädter LT, Coenen M, Visscher C, Kamphues J. Investigations on the Effects of Different Calcium Supply Exceeding the Requirements on Mineral Serum Concentrations and Bone Metabolism in Young Warmblood Stallions. Animals (Basel) 2021 Aug 19;11(8).
                  doi: 10.3390/ani11082439pubmed: 34438897google scholar: lookup
                3. Hunter BG, Duesterdieck-Zellmer KF, Larson MK. Tiludronate concentrations and cytologic findings in synovial fluid after intravenous regional limb perfusion with tiludronate in horses. PeerJ 2015;3:e889.
                  doi: 10.7717/peerj.889pubmed: 25945303google scholar: lookup
                4. Delguste C, Doucet M, Gabriel A, Guyonnet J, Lepage OM, Amory H. Assessment of a bone biopsy technique for measuring tiludronate in horses: a preliminary study. Can J Vet Res 2011 Apr;75(2):128-33.
                  pubmed: 21731184
                5. Tou K, Cawley A, Noble G, Loy J, Bishop D, Keledjian J, Sornalingam K, Richards S, Fu S. Lipid and Corticosteroid Biomarkers Under the Influence of Bisphosphonates. Drug Test Anal 2025 Jul;17(7):1107-1117.
                  doi: 10.1002/dta.3811pubmed: 39407358google scholar: lookup
                6. Ayodele BA, Pagel CN, Mackie EJ, Armour F, Yamada S, Zahra P, Courtman N, Whitton RC, Hitchens PL. Differences in bone turnover markers and injury risks between local and international horses: A Victorian Spring Racing Carnival study. Equine Vet J 2025 Mar;57(2):333-346.
                  doi: 10.1111/evj.14098pubmed: 38634210google scholar: lookup