Intraosseous infusion of the distal phalanx compared to systemic intravenous infusion for marimastat delivery to equine lamellar tissue.
Authors: Underwood Claire, Collins Simon N, van Eps Andrew W, Mills Paul C, Allavena Rachel E, Bailey Simon R, Medina Torres Carlos E, Meizler Alon, Pollitt Christopher C
Journal: Veterinary journal (London, England : 1997)
Summary
# Editorial Summary: Intraosseous versus Systemic Marimastat Delivery in Equine Laminitis Despite the clinical urgency of laminitis prevention, no approved pharmacological treatment exists, partly because many promising agents cannot be safely given systemically at therapeutic doses. Underwood and colleagues compared two delivery routes—intraosseous infusion directly into the distal phalanx (IOIDP) versus systemic intravenous constant rate infusion (CRI)—to establish which could achieve higher marimastat concentrations in lamellar tissue, where this matrix metalloproteinase inhibitor might prevent enzymatic breakdown of the lamellae. Using ultrafiltration probes to sample lamellar interstitial fluid in five horses, they found that both routes achieved equivalent steady-state marimastat concentrations (139 and 136 ng/mL respectively), with IOIDP showing inconsistent drug delivery and no local concentration advantage over the treated foot, untreated foot, or plasma. Critically, concentrations achieved by both methods exceeded the IC₅₀ for MMP-2 and MMP-9 inhibition but fell below levels considered necessary for in vivo prevention of laminitis. For practitioners, this work reveals that direct intraosseous administration offers no pharmacokinetic advantage over systemic delivery for marimastat, and more fundamentally, that current dosing and delivery strategies may be insufficient to achieve therapeutic effect—suggesting that alternative compounds, modified techniques, or substantially higher doses warrant investigation before pursuing IOIDP as a clinical intervention.
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Practical Takeaways
- •Local intraosseous infusion to the distal phalanx does not currently offer an advantage over systemic intravenous infusion for delivering marimastat to lamellar tissue, and drug delivery by this route is unreliable
- •Neither delivery method achieved sufficient marimastat concentrations in lamellar tissue to prevent laminitis based on current knowledge, suggesting alternative drugs, dosing strategies, or delivery methods need further investigation
- •Until the IOIDP technique is refined and validated, systemic drug administration remains the more predictable approach for laminitis prevention, though better therapeutic options are still needed
Key Findings
- •Intraosseous infusion of the distal phalanx (IOIDP) and systemic intravenous constant rate infusion (CRI) achieved similar steady-state marimastat concentrations in lamellar ultrafiltrate (139 ng/mL vs 136 ng/mL respectively)
- •Marimastat concentrations achieved by both IOIDP and CRI exceeded the IC50 for lamellar MMP-2 and MMP-9 but fell below the concentration considered necessary for in vivo laminitis prevention
- •IOIDP delivery was inconsistent and failed to achieve preferential drug accumulation in the treated foot compared to the untreated foot or plasma
- •Modification of the IOIDP technique is necessary to achieve consistent and therapeutically superior local drug delivery to lamellar tissue