Effect of induced synovial inflammation on pharmacokinetics and synovial concentration of sodium ampicillin and kanamycin sulfate after systemic administration in ponies.

This study investigates how inflamed joints in ponies affect the distribution and absorption of two antibiotics, sodium ampicillin and kanamycin sulfate, when administered together.

Research Methodology

• The research was conducted on five pony mares. Each was given single doses of sodium ampicillin and kanamycin sulfate, separately and then together.
• The doses were administered intramuscularly, and the concentrations of the antibiotics in the ponies’ blood were measured over time to construct plasma concentration-time curves. This method allowed researchers to observe the pharmacokinetics of the drugs – how the body absorbs, distributes, metabolizes and excretes the antibiotics.
• Four ponies were then injected with lipopolysaccharide in their left intercarpal joint to induce synovitis, a condition characterized by joint inflammation and fever, before being administered the combination of antibiotics. The concentrations of the drugs in the plasma and synovial fluid, the lubricating fluid found in the joints, were then measured over time.

Key Findings

• It was found that the pharmacokinetic parameters of each drug given separately were not altered when administered concurrently, indicating that the two antibiotics do not interfere with each other’s absorption and distribution in the body.
• The lipopolysaccharide-induced inflammation significantly impacted the absorption of the drugs, as evidenced by the higher maximum concentration (Cmax) of ampicillin found in the synovial fluid after such administration.
• The inflamed joint absorbed the antibiotics at a quicker rate and at higher concentrations compared to a healthy joint. Specifically, the concentration of ampicillin exceeded 5 micrograms/ml in inflamed synovial fluid for about 2.5 hours after injection, while the concentration of kanamycin sulfate exceeded 2 micrograms/ml for seven hours.

Conclusions

• The study suggests that when a joint is inflamed, it absorbs antibiotics more readily. This can potentially enhance the effectiveness of these drugs against bacterial infections in the synovium.
• This research could help to inform veterinary treatment approaches when treating joint infections in equine patients, potentially leaning toward the concurrent use of ampicillin and kanamycin sulfate for enhanced drug uptake in the presence of synovial inflammation.