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Concentration of Marbofloxacin in equine subcutaneous tissue fluid after subcutaneous administration in encapsulated
Hiroshi Mita1, Taisuke Kuroda1, Yohei Minamijima2
1Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Tochigi, 329-0412, Japan.
Abstract:
Surgical-site infections (SSIs) at implant sites in horses are sometimes difficult to control with systemic antimicrobials. Because one of the likely reasons is insufficient antimicrobial concentrations, there is a need to increase these concentrations in and around the infected tissue. Marbofloxacin (MAR)-encapsulated microparticles (MAR-MPs) made of biodegradable poly (lactic-co-glycolic) acid are capable of sustained release in vitro. We examined the concentration of MAR in the subcutaneous tissue fluid at sites where MAR-MPs had been administered. On day 0, six 3- × 4-cm subcutaneous pockets were created in the neck of each of six Thoroughbred horses under sedation and local anesthesia. MAR-MPs containing 50 mg of MAR were added to each pocket, which was then sutured. On days 1, 2, 3, 4, and 7, subcutaneous tissue fluid from one pocket per horse was collected and analyzed by LC-MS/MS. From days 1 to 7, the median MAR concentration in the subcutaneous tissue fluid ranged from 17.7 (4.89-125.6) to 33.05 (15.1-71.6) µg/mL. The median concentrations in the subcutaneous tissue fluid exceeded the MIC90 (the minimum inhibitory concentration that would inhibit the growth of 90 % of the tested bacterial isolates) of MAR for clinical isolates reported previously. The area of swelling at the site of administration was significantly larger on days 1 to 4 than just after administration (P < 0.05). MAR-MPs could be useful for controlling SSIs that require high antimicrobial concentrations for extended periods when they are used with strategies that reduce side effects.
Insights
Marbofloxacin-encapsulated microparticles deliver sustained high concentrations of marbofloxacin in horse subcutaneous tissue, exceeding bacterial minimum inhibitory concentrations. This approach may help control difficult surgical-site infections.
Area of Science:
- Veterinary Medicine
- Pharmacology
- Biomaterials
Background:
- Surgical-site infections (SSIs) in horses are challenging to treat with systemic antimicrobials due to insufficient drug concentrations at the infection site.
- Biodegradable poly(lactic-co-glycolic) acid microparticles offer sustained release of marbofloxacin (MAR-MPs).
Purpose of the Study:
- To evaluate the concentration of marbofloxacin in subcutaneous tissue fluid following administration of MAR-MPs in horses.
- To determine if MAR-MP administration achieves concentrations exceeding the minimum inhibitory concentration (MIC90) for relevant bacterial isolates.
Main Methods:
- Subcutaneous pockets were created in six horses, and MAR-MPs (50 mg MAR) were administered.
- Subcutaneous tissue fluid was collected from days 1 to 7 and analyzed for MAR concentration using LC-MS/MS.
- Swelling at administration sites was measured and compared to baseline.
Main Results:
- Median MAR concentrations in subcutaneous tissue fluid ranged from 17.7 to 33.05 µg/mL between days 1 and 7.
- These concentrations consistently exceeded the reported MIC90 of MAR for clinical bacterial isolates.
- A significant increase in local swelling was observed from days 1 to 4.
Conclusions:
- MAR-MPs provide sustained release of marbofloxacin in equine subcutaneous tissue, achieving effective concentrations.
- This delivery method shows potential for managing SSIs requiring prolonged high antimicrobial levels.
- Further strategies may be needed to mitigate local side effects like swelling.
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