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

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ABSTRACT Intraarticular administration of vancomycin is increasingly used to achieve high local antibiotic concentrations in orthopaedic procedures; however, its pharmacokinetic behavior in periarticular tissues remains poorly defined. This study employed in‐vivo microdialysis to quantify vancomycin concentrations in plasma, bone, muscle, and subcutaneous following a single intraarticular injection in a rat model. Vancomycin (5 mg/100 µL) was administered into the knee joint, and microdialysis sampling was performed for up to 5 h. Liquid chromatography–tandem mass spectrometry was used to determine pharmacokinetic parameters including C max , T max , AUC 0–last , and T 1/2 . Vancomycin was detected in all compartments, with the highest exposure observed in plasma (AUC 0–24h : 2783 ± 600 min·µg/mL, C max : 9 ± 2 µg/mL), followed by muscle, bone, and subcutaneous. Muscle exhibited the greatest local exposure (AUC 0–5h : 965 ± 442 min·µg/mL), while only subcutaneous showed significantly lower C max values compared to plasma ( p = 0.0333). These findings provide key insights into the local and systemic pharmacokinetics of intraarticularly delivered vancomycin in a rodent model. The differences between the concentrations observed in different peri‐articular tissues should be considered in interpreting the efficacy of intra‐articular treatments for clinical use. Statement of Clinical Significance This pilot study represents a critical advancement in the monitoring of local drug concentrations by in‐vivo microdialysis when evaluating intraarticular antibiotic delivery. This method can significantly enhance the development of effective, localized treatment protocols by providing more accurate predictions of tissue and administration‐specific drug concentrations and efficacy. The results provide important information on achievable tissue concentrations using local delivery of vancomycin. The determination of local concentrations achieved by sustained local delivery devices can aid in improved delivery profiles to improve patient outcomes in the prevention and management of orthopedic infections.

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