In vitro and in vivo evaluation of ferric-hyaluronate implants for delivery of amikacin sulfate to the tarsocrural joint of horses.

OBJECTIVE: To assess the antimicrobial elution characteristics, toxicity, and antimicrobial activity of amikacin-impregnated ferric-hyaluronate implants (AI-FeHAI) for amikacin delivery to the tarsocrural joint of horses. STUDY DESIGN: Experimental study. SAMPLE POPULATION: AI-FeHAI implants, equine cartilage, and synovium, and horses (n=6). METHODS: In vitro study: Five AI-FeHAI were placed in saline solution with daily replacement until implant degradation. Eluent was tested for amikacin concentration and bioactivity. Synovial and cartilage explants were incubated in the presence or absence of AI-FeHAI for 72 hours and subsequently assessed for morphology, viability, and composition. Synovial explants were incubated with Staphylococcus aureus in the presence or absence of AI-FeHAI. Spent medium was cultured daily and explants were assessed for morphology and viability after 96 hours. In vivo study: AI-FeHAI were placed in 6 tarsocrural joints. Standard cytologic analysis and amikacin concentration (SFAC) were determined in synovia obtained regularly for 28 days thereafter. Similar analyses were conducted after a single intra-articular injection of amikacin 6 months later. RESULTS: In vitro study: Amikacin concentrations exceeded 16 microg/mL and inhibited S. aureus growth for 8 days. AI-FeHAI had no effect on cartilage explants. AI-FeHAI eliminated bacteria from synovial explants. In vitro study: After AI-FeHAI placement, SFAC was highest (140.78+63.81 microg/mL) at first sampling time. By 24 hours SFAC was <16 microg/mL. After intra-articular injection, SFAC was the highest (377.91 +/- 40.15 microg/mL) at first sampling time. By 48 hours SFAC was <16 microg/mL. CONCLUSIONS: A single intra-articular amikacin injection demonstrated superior pharmacokinetics than AI-FeHAI prepared as described. CLINICAL RELEVANCE: AI-FeHAI cannot be recommended for clinical use.

Comparison of intraosseous and intravenous infusion of technetium Tc 99m pertechnate in the distal portion of forelimbs in standing horses by use of scintigraphic imaging.

OBJECTIVE: To describe and compare the distribution of technetium Tc 99m (99mTc) pertechnate following intraosseous or i.v. injection (with or without use of a tourniquet) in the distal portion of the forelimb in standing horses. ANIMALS: 4 horses. PROCEDURE: Each horse received 4 forelimb treatments in random sequence: intraosseous infusion with tourniquet application (IOT), intraosseous infusion without tourniquet application, i.v infusion with tourniquet application (IVT), and i.v. infusion without tourniquet application. Dynamic nuclear scintigraphic imaging of the third metacarpal bone, proximal and middle phalanges, and distal phalanx was performed from the start of each treatment until 1 hour after infusion was completed. Radionuclide activity was compared within and between treatment groups. RESULTS: Tourniquet application was necessary to maintain high levels of radionuclide activity in the distal portion of the forelimb after intraosseous or i.v. infusion with 99mTc pertechnate; IVT and IOT treatments resulted in similar radionuclide activity in the proximal and middle phalanges and distal phalanx. Of the 4 treatments, there was significantly higher radionuclide activity in the distal aspect of the third metacarpal bone after the IOT treatment. CONCLUSIONS AND CLINICAL RELEVANCE: By use of a tourniquet, radionuclide administration via the intraosseous or i.v. routes resulted in effective perfusion of the distal portion of the forelimb and similar distribution of the agent in the phalanges of horses. Further studies are required to ascertain whether these findings apply to delivery of therapeutic agents in infected tissues via IOT or IVT.