ABSTRACT
Intraosseous (i.o.) infusion of the distal phalanx (IOIDP) as a delivery route targeting hoof lamellar tissue of standing, conscious horses was evaluated. Following sedation and regional nerve blockade in six Standardbred horses, a microdialysis (MD) probe was implanted into the hoof lamellar tissue of one forelimb. A purpose designed cannulated bone screw was introduced into the body of the distal phalanx, approximately 6 cm from the MD probe. Gentamicin solution (25 mg/mL) was infused at 20 microL/min through the bone screw for 2 h without the application of a tourniquet. MD and blood samples were collected at regular intervals and analysed for gentamicin concentrations. Gentamicin was present in lamellar tissue at much higher concentrations than peripheral serum. The mean concentration of gentamicin was 24.4, 20.5 and 4.4 microg/mL in extracellular fluid (ECF) and 0.28, 0.5 and 0.32 microg/mL in serum samples collected 60, 120 and 150 min after IOIDP was started, respectively. A clinically safe and efficacious i.o. drug delivery to the hoof lamellar tissue of standing, conscious horse was developed.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Gentamicins/pharmacokinetics , Infusions, Intraosseous/veterinary , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Bone Screws/veterinary , Consciousness , Foot Diseases/drug therapy , Foot Diseases/veterinary , Forelimb , Gentamicins/administration & dosage , Gentamicins/therapeutic use , Hoof and Claw , Horse Diseases/drug therapy , Horses , Inflammation/drug therapy , Inflammation/veterinary , Infusions, Intraosseous/methods , Lameness, Animal/metabolism , Male , Microdialysis/veterinary , Posture , Tourniquets/veterinaryABSTRACT
Microdialysis (MD) was used for continuous monitoring of the lamellar extracellular fluid (ECF) in six mature healthy Standardbred horses. MD probes were introduced into the lamellar tissue under local anaesthesia. Following intravenous injection of gentamicin (5mg/kg), MD and serum samples were collected for 24h and analysed using a sensitive ELISA test for gentamicin and fluorescence polarization immunoassay for urea concentrations. Calibration of probes was performed through in vivo urea recovery and in vitro gentamicin and urea recovery. Data obtained from different body compartments were compared statistically. The concentration of gentamicin was significantly higher in serum than lamellar ECF for the first 8h (P<0.05), but remained above the minimum inhibitory concentration (MIC) in the ECF for a further 4h. The method will be useful to monitor changes in the lamellar ECF during laminitis and the local kinetics of drugs used therapeutically for this condition.
