Intraosseous infusion of the distal phalanx compared to systemic intravenous infusion for marimastat delivery to equine lamellar tissue.
Abstract: No validated laminitis drug therapy exists, yet pharmaceutical agents with potential for laminitis prevention have been identified. Many of these are impractical for systemic administration but may be effective if administered locally. This study compared intraosseous infusion of the distal phalanx (IOIDP) with systemic intravenous constant rate infusion (CRI) to determine which was more effective for lamellar marimastat delivery. Ultrafiltration probes were placed in both forefeet of five horses to collect lamellar interstitial fluid as lamellar ultrafiltrate (LUF). Marimastat solution (3.5 mg/mL) containing lidocaine (20 mg/mL) was infused by IOIDP at 0.15 mL/min for 12 h. After a 12 h wash-out, marimastat (3.5 mg/mL) and lidocaine were infused by constant rate infusion (CRI) at 0.15 mL/min for 12 h. LUF, plasma and lamellar tissue marimastat concentrations were quantified using UPLC-MS. Zymography was used to establish the inhibitory concentrations of marimastat for equine lamellar matrix metalloproteinases (MMPs). Data were analysed non-parametrically. There was no difference between the steady-state marimastat concentration in lamellar ultrafiltrate (LUF[M]) during IOIDP (139[88-497] ng/mL) and CRI (136[93-157] ng/mL). During IOIDP, there was no difference between marimastat concentrations in the treated foot (139[88-497] ng/mL), the untreated foot (91[63-154] ng/mL) and plasma (101[93-118] ng/mL). LUF[M] after IOIDP and CRI were >IC50 of lamellar MMP-2 and 9, but below the concentration considered necessary for in vivo laminitis prevention. Lamellar drug delivery during IOIDP was inconsistent and did not achieve higher lamellar marimastat concentrations than CRI. Modification or refinement of the IOIDP technique is necessary if it is to be consistently effective.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication Date: 2015-05-19 PubMed ID: 26073286DOI: 10.1016/j.tvjl.2015.05.010Google Scholar: Lookup
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- Clinical Trial
- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article can be summarized as an exploration into methods of marimastat drug delivery into lamellar tissue of horses to prevent laminitis. The study compared intraosseous infusion and systemic intravenous infusion to find which was more effective, but concluded both methods were similar in marimastat concentration delivery but fell short of the necessary amount for laminitis prevention, suggesting further refinement of delivery methods is required.
Study Overview and Aim
- The study aims to fill a gap in the therapeutic treatment of laminitis in horses. No validated drug therapy currently exists.
- The objective is to investigate more practical methods of administering laminitis preventative agents by comparing the effectiveness of intraosseous infusion (IOIDP) and systemic intravenous constant rate infusion (CRI) in delivering the drug marimastat to equine lamellar tissue.
Methods
- Experimental design consists of both types of infusions in five horses with ultrafiltration probes placed in each horse to collect lamellar interstitial fluid for analysis.
- Marimastat is combined with lidocaine and delivered at equal rates via both methods, with a 12-hour wash-out period in between treatments.
- The measurement of marimastat concentration in lamellar ultrafiltrate (LUF), plasma and lamellar tissue is done using UPLC-MS.
- Zymography is used to determine the inhibitory concentrations of marimastat on equine lamellar matrix metalloproteinases (MMPs).
Results
- The results indicate no significant difference in the delivery of marimastat using IOIDP versus CRI.
- Both methods delivered marimastat above the inhibitory concentration for lamellar MMP-2 and 9, enzymes that are involved in the development of laminitis.
- However, the concentrations fell below the necessary levels for preventing laminitis in vivo, indicating that both methods are ineffective as currently practiced.
Conclusion
- The study concludes that while IOIDP and CRI methods of drug delivery are similar in effectiveness, neither achieved a high enough concentration of marimastat for laminitis prevention.
- This underscores the need for further refinement or modification of drug delivery techniques to enable effective laminitis prevention therapies in horses.
Cite This Article
APA
Underwood C, Collins SN, van Eps AW, Mills PC, Allavena RE, Bailey SR, Medina Torres CE, Meizler A, Pollitt CC.
(2015).
Intraosseous infusion of the distal phalanx compared to systemic intravenous infusion for marimastat delivery to equine lamellar tissue.
Vet J, 205(3), 357-363.
https://doi.org/10.1016/j.tvjl.2015.05.010 Publication
Researcher Affiliations
- Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia. Electronic address: c.underwood1@uq.edu.au.
- Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
- Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
- Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
- Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
- Faculty of Veterinary Science, The University of Melbourne, Werribee, Victoria, Australia.
- Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
- Innovative Methods (Queensland) Ltd., 27 Price Street, Riverview, Queensland, Australia.
- Australian Equine Laminitis Research Unit, School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
MeSH Terms
- Animals
- Female
- Foot Diseases / veterinary
- Hoof and Claw
- Horse Diseases / drug therapy
- Horses
- Hydroxamic Acids / administration & dosage
- Hydroxamic Acids / therapeutic use
- Infusions, Intraosseous / veterinary
- Infusions, Intravenous / veterinary
- Male
- Matrix Metalloproteinase Inhibitors / administration & dosage
- Matrix Metalloproteinase Inhibitors / therapeutic use
Citations
This article has been cited 1 times.- Chen J, Zhang C, He X, Han X, Su Y, Chen C, Xu W, Yang W. Intraosseous versus intravenous fluid resuscitation in gastrointestinal tumor-related acute hemorrhage: impact on 30-day mortality and lactate clearance. Am J Cancer Res 2025;15(6):2682-2700.
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