Dynamically calibrated microdialysis for investigating drug penetration in juvenile pigs : advancing pediatric antibiotic research

Introduction: Antibiotics are essential for treating bacterial infections, but understanding their target tissue concentrations is crucial for optimizing efficacy, particularly in understudied populations like children. Microdialysis (µD) is the gold standard for measuring tissue drug concentrations; however, in vivo robustness and calibration validation remain underexplored despite their importance, as current in vitro data show low translatability. Juvenile pig models provide reliable pediatric pharmacokinetic (PK) predictions. This study evaluated plasma and tissue cefazolin (CFZ) concentrations in piglets and assessed the impact of different µD calibration techniques. Methods: Six piglets received jugular catheters and µD probes in muscle and adipose tissue. Following a CFZ bolus (30 mg/kg, IV), µD calibration was performed using the internal standards cefuroxime (CFR) or ceftezole (CFTZ). Plasma and µD samples were analyzed via LC-MS/MS, and Pharmacokinetic modeling assessed tissue penetration and the impact of IS selection. Results: CFR and CFTZ calibration yielded consistent relative recoveries (~73%). Linear mixed model showed that tissue penetration ratios were significantly influenced by IS choice (p=0.002) and tissue type (p=0.016). Conclusions: This study confirms the feasibility of µD for evaluating tissue drug disposition in piglets. The findings highlight the importance of IS selection and tissue type in µD calibration and similar penetration values reinforce the piglet model’s relevance for pediatric PK research.