In Vivo Microdialysis Assessment of Systemic and Local Vancomycin Levels Following Intraarticular Administration in...

Area of Science:

• Pharmacology
• Orthopedics
• Drug Delivery

Background:

• Intraarticular vancomycin is used in orthopedics for high local antibiotic concentrations.
• Pharmacokinetics in periarticular tissues are not well-defined.

Purpose of the Study:

• Quantify vancomycin concentrations in plasma and periarticular tissues (bone, muscle, subcutaneous) after intraarticular injection.
• Determine pharmacokinetic parameters using in-vivo microdialysis in a rat model.

Main Methods:

• Single intraarticular injection of vancomycin (5 mg/100 µL) into the knee joint of rats.
• In-vivo microdialysis for sampling in plasma, bone, muscle, and subcutaneous tissue for up to 5 hours.
• Liquid chromatography-tandem mass spectrometry for pharmacokinetic analysis (Cmax, Tmax, AUC0-last, T1/2).

Main Results:

• Vancomycin was detected in all compartments.
• Highest exposure was in plasma (AUC0-24h: 2783 ± 600 min·µg/mL).
• Muscle showed the greatest local exposure (AUC0-5h: 965 ± 442 min·µg/mL). Subcutaneous tissue had significantly lower Cmax than plasma (p=0.0333).

Conclusions:

• This study provides key insights into the local and systemic pharmacokinetics of intraarticular vancomycin in rats.
• Differences in tissue concentrations should be considered for clinical efficacy interpretation.
• In-vivo microdialysis advances monitoring of local drug concentrations for orthopedic infection treatment protocols.