Tiludronate concentrations and cytologic findings in synovial fluid after intravenous regional limb perfusion with tiludronate in horses.
Abstract: Anecdotal accounts of tiludronate administration via intravenous regional limb perfusion (IVRLP) exist despite a lack of information regarding safety for synovial structures in the perfused area. The objective of this study was to determine whether tiludronate concentrations in synovial structures after IVRLP with low dose (0.5 mg, LDT) or high dose (50 mg, HDT) tiludronate remain below a value demonstrated in vitro to be safe for articular cartilage (<19,000 ng/ml), and to determine effects of tiludronate on synovial fluid cytology variables compared to saline perfused control limbs. Using a randomized controlled experimental study design, horses received IVRLP with LDT (n = 6) or HDT (n = 6) in one forelimb and IVRLP with saline in the contralateral limb. Synovial fluid cytology variables and tiludronate concentrations were evaluated in navicular bursae (NB), and distal interphalangeal (DIP) and metacarpophalangeal (MCP) joints one week before and 30-45 min after IVRLP, and in DIP and MCP joints 24 h after IVRLP. Data were analyzed with 2-way rmANOVA (p 19,000 ng/ml in DIP joints of two HDT limbs. Tiludronate was measurable only in synovial fluid from HDT limbs 24 h post-perfusion. There were no differences in synovial fluid cytology variables between control and treated limbs. Conclusions. In some horses, IVRLP with HDT may result in synovial fluid concentrations of tiludronate that may have adverse effects on articular cartilage, based on in vitro data. IVRLP with LDT is unlikely to promote articular cartilage degradation. Further studies to determine a safe and effective dose for IVRLP with tiludronate are needed.
Publication Date: 2015-04-28 PubMed ID: 25945303PubMed Central: PMC4419440DOI: 10.7717/peerj.889Google Scholar: Lookup
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- Journal Article
- Adverse Effects
- Articular Cartilage
- Clinical Study
- Cytology
- Disease Treatment
- Distal Interphalangeal Joint
- Drug
- Equine Health
- Experimental Methods
- Horses
- In Vitro Research
- In Vivo
- Intravenous Administration
- Metacarpophalangeal Joint
- Navicular Bone
- Pharmacokinetics
- Pharmacology
- Random
- Synovial Fluid
- Veterinary Medicine
Summary
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The research explores the safety of tiludronate, administered to horses through intravenous regional limb perfusion (IVRLP). The aim was to assess whether tiludronate concentrations remained below a safe threshold for articular cartilage, and to examine its effects on synovial fluid cytology variables.
Objective and Methodology
- The objective this study was to measure the concentration of tiludronate, a drug commonly used in horses, in the synovial structures following IVRLP.
- The study aimed to establish whether the concentration levels remained within an in vitro safe threshold for articular cartilage, that is under 19,000 nanograms per milliliter (ng/ml).
- Furthermore, the study aimed to assess the effects of tiludronate on synovial fluid cytology variables, comparing it to saline-perfused control limbs.
- To achieve these goals, the researchers employed a controlled experimental design, administering tiludronate to horses at both low (0.5 milligram, LDT) and high (50 milligram, HDT) doses.
Results and Findings
- After administration, the synovial fluid cytology variables and tiludronate concentrations were evaluated in three different areas: the navicular bursae (NB), the distal interphalangeal (DIP) and the metacarpophalangeal (MCP) joints of horses. This occurred one week before, and 30-45 minutes and 24 hours after IVRLP.
- The peak concentration of tiludronate in the synovial fluid was found 30-45 minutes after perfusion.
- Mean tiludronate concentrations significantly differed based on the administered dosage, with lesser concentrations in LDT limbs compared to the HDT ones.
- In the DIP joints of two horses who received the high dose treatment, the tiludronate concentration exceeded the safe limit of 19,000 ng/ml.
- After 24 hours, tiludronate was only detectable in the synovial fluid of HDT limbs.
- No notable differences were observed in synovial fluid cytology variables between the control and treated limbs.
Conclusions and Further Research
- The study concluded that IVRLP with a high dose of tiludronate may result in concentrations which could potentially harm the articular cartilage of horses.
- However, administration with a low dose of tiludronate is unlikely to cause cartilage degradation.
- As such, further studies are needed to establish a safe and effective dose for IVRLP administration of tiludronate.
Cite This Article
APA
Hunter BG, Duesterdieck-Zellmer KF, Larson MK.
(2015).
Tiludronate concentrations and cytologic findings in synovial fluid after intravenous regional limb perfusion with tiludronate in horses.
PeerJ, 3, e889.
https://doi.org/10.7717/peerj.889 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University , Corvallis, OR , USA.
- Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University , Corvallis, OR , USA.
- Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University , Corvallis, OR , USA.
Conflict of Interest Statement
The authors declare there are no competing interests.
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Citations
This article has been cited 1 times.- Mizobe F, Nomura M, Kato T, Nambo Y, Yamada K. Signal changes in standing magnetic resonance imaging of osseous injury at the origin of the suspensory ligament in four Thoroughbred racehorses under tiludronic acid treatment. J Equine Sci 2017;28(3):87-97.
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