Intra-articular injection of an extended-release flavopiridol formulation represents a potential alternative to other intra-articular medications for treating equine joint disease.
Abstract: To establish the pharmacokinetics of the cyclin-dependent kinase-9 inhibitor flavopiridol in equine middle carpal joints, using an extended-release poly lactic-co-glycolic acid (PLGA) microparticle formulation. Methods: 4 healthy horses without evidence of forelimb lameness. Methods: A 6-week longitudinal pharmacokinetic study was conducted in 2 phases (6 weeks each) in 4 healthy horses. The PLGA microparticles containing 122 μg flavopiridol in 3 mL saline were administered by intra-articular injection into 1 middle carpal joint, with empty PLGA microparticles injected into the contralateral joint as a control. Synovial fluid and plasma were collected at time points out to 6 weeks, and drug concentrations in synovial fluid and plasma were determined using validated protocols. Synovial fluid total protein and total nucleated cell count and differential, CBC, serum biochemistry, and lameness exams were performed at each of the time points. Results: Synovial fluid flavopiridol averaged 19 nM at week 1, gradually reduced to 1.4 nM by 4 weeks, and was generally below the detection limit at 5 and 6 weeks. There was no detectable flavopiridol in the plasma samples, and no adverse effects were observed at any time point. Conclusions: Intra-articular injection of PLGA microparticle-encapsulated flavopiridol was well tolerated in horses, with detectable levels of flavopiridol in the synovial fluid out to 4 weeks with negligible systemic exposure. Flavopiridol is a cyclin-dependent kinase-9 inhibitor with potent anti-inflammatory and analgesic activity. The extended-release microparticle formulation promotes intra-articular retention of the drug and it may be an alternative to other intra-articular medications for treatment of equine joint disease.
Publication Date: 2024-06-21 PubMed ID: 38906170DOI: 10.2460/ajvr.24.03.0057Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
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 researchers examined the effects of a potential new treatment for equine joint disease. They did this by injecting a solution that includes the drug flavopiridol, encapsulated within small particles, into the joints of healthy horses. The drug was released over time, and the research showed that it remained in the joint area for up to four weeks with minimal absorption into the bloodstream, which suggests it could offer a sustained, localised treatment for joint issues in horses.
Objective and Methodology
- The study aimed to understand the behavior, effectiveness, and possible side effects of a new application of the drug, flavopiridol, in treating equine joint diseases.
- Flavopiridol, known for its anti-inflammatory and analgesic properties, was presented in an extended-release formulation using PLGA (poly lactic-co-glycolic acid) microparticles.
- A total of four healthy horses were used for this study, with a saline solution containing flavopiridol introduced into one joint, and a control saline solution without flavopiridol injected into the opposite joint.
- The research was conducted in two phases (each lasting six weeks), during which samples of synovial fluid and blood were collected at different points for analysis.
- The researchers measured drug concentration, protein levels, and cell count in synovial fluid to monitor the presence and potential effects of the drug.
- Comprehensive biochemistry tests and observations for signs of lameness were also performed at each time point to assess if any systemic side effects occurred.
Findings and Conclusion
- The results showed that detectable levels of flavopiridol remained in the synovial fluid up to four weeks post-injection.
- The concentration of the drug gradually decreased over the period, becoming almost undetectable by weeks five and six.
- No systemic absorption of the drug was found, meaning it didn’t enter the horses’ general bloodstream – a positive outcome considering the intention is for the drug to treat local joint issues.
- Importantly, no adverse effects or signs of lameness were observed in any of the horses during the study.
- The findings suggest that flavopiridol, when used in an extended-release PLGA microparticle formulation, can provide a localized, sustained presence in joint areas, making it a potential alternative for treating equine joint diseases.
Cite This Article
APA
Katzman SA, Cissell D, Leale D, Perez-Nogues M, Hall MD, Bloom G, Hamamoto-Hardman B, Wu CY, Haudenschild AK, Liu GY, Yik JHN, Haudenschild DR.
(2024).
Intra-articular injection of an extended-release flavopiridol formulation represents a potential alternative to other intra-articular medications for treating equine joint disease.
Am J Vet Res, 85(9).
https://doi.org/10.2460/ajvr.24.03.0057 Publication
Researcher Affiliations
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA.
- Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California-Davis, Davis, CA.
- Department of Orthopedic Surgery, School of Medicine, University of California-Davis, Davis, CA.
- William R. Pritchard Veterinary Medical Teaching Hospital, University of California-Davis, Davis, CA.
- William R. Pritchard Veterinary Medical Teaching Hospital, University of California-Davis, Davis, CA.
- William R. Pritchard Veterinary Medical Teaching Hospital, University of California-Davis, Davis, CA.
- William R. Pritchard Veterinary Medical Teaching Hospital, University of California-Davis, Davis, CA.
- Bioanalysis and Pharmacokinetics Core Facility, University of California-Davis, Davis, CA.
- Department of Orthopedic Surgery, School of Medicine, University of California-Davis, Davis, CA.
- Department of Chemistry, University of California-Davis, Davis, CA.
- Department of Orthopedic Surgery, School of Medicine, University of California-Davis, Davis, CA.
- Houston Methodist Research Institute, Orthopedics and Sports Medicine, Houston, TX.
- Department of Orthopedic Surgery, School of Medicine, University of California-Davis, Davis, CA.
- Houston Methodist Research Institute, Orthopedics and Sports Medicine, Houston, TX.
MeSH Terms
- Animals
- Horses
- Injections, Intra-Articular / veterinary
- Flavonoids / administration & dosage
- Flavonoids / pharmacokinetics
- Horse Diseases / drug therapy
- Delayed-Action Preparations
- Piperidines / administration & dosage
- Piperidines / pharmacokinetics
- Piperidines / therapeutic use
- Synovial Fluid
- Joint Diseases / veterinary
- Joint Diseases / drug therapy
- Male
- Female
- Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
- Longitudinal Studies
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
