Intraosseous Infusion of the Distal Phalanx and Lamellar Microdialysis: New Techniques for Lamellar Drug Delivery and Analysis

Article Outline

• Take Home Message
• Introduction
• Materials & Methods
• Results
• Discussion
• Clinical Relevance
• Copyright

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Take Home Message 

IOIDP and LMD are viable techniques for lamellar drug delivery and analysis.

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Introduction 

Seeking a new approach to laminitis drug delivery we developed and validated intraosseous infusion of the distal phalanx (IOIDP). Lamellar microdialysis (LMD) enabled analysis of lamellar constituents.

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Materials & Methods 

Under regional nerve blockade a microdialysis (MD) probe was implanted into the hoof lamellar tissue of six sedated, healthy, Standardbred horses. An intraosseous screw was introduced into the body of the distal phalanx and gentamicin (25 mg/mL at 20 μL/ min) was infused for two hours without a tourniquet. MD and blood samples were collected and analysed for gentamicin concentrations. In another experiment radiopaque contrast media was infused, without the application of a distal limb tourniquet, to validate lamellar delivery.

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Results 

Gentamicin was present in lamellar tissue at much higher concentrations than serum. The mean concentration of gentamicin was 24.4, 20.5 and 4.4 μg/mL in lamellar extracellular fluid (ECF) and 0.28, 0.5 and 0.32 μg/mL in serum samples collected 60, 120 and 150 min after the IO infusion was started, respectively. Contrast media was present in the sublamellar dermis immediately after infusion.

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Discussion 

IOIDP delivered gentamicin at high concentration directly to the lamellar ECF and lamellar delivery was validated by contrast radiography. A vascular relationship exists between the interior of the distal phalanx and the lamellar circulation that can be used for lamellar drug delivery.

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Clinical Relevance 

Slow IOIDP is a clinically viable method of delivering drugs directly to the lamellar circulation in the standing, conscious horse. Changes in the lamellar ECF during laminitis and the local kinetics of drugs used therapeutically for this condition can be monitored via LMD.