Microdialysis to study tissue penetration of drugs in the juvenile pig : an opportunity for pediatric drug research

Objectives Juvenile pig models have proven to provide an accurate and reliable prediction of pediatric pharmacokinetic behavior. Microdialysis is currently the gold standard for studying drug concentrations in tissues. In microdialysis a small probe, consisting of a semipermeable hollow fiber membrane, is implanted into the tissue of interest. Mainly because of the invasiveness of microdialysis, data on tissue distribution of drugs remains largely understudied in children. The aim of this pilot study was to investigate the feasibility of multiple day microdialysis in awake and free moving piglets. Methods Six piglets of four weeks old were individually housed in pens. During short sedation a microdialysis probe was implanted in the paraspinal musculature under ultrasound guidance. Thereafter, the microdialysis pump was connected and fixated on the body by means of an elastic band encircling the thorax. Over the course of four days intravenous antibiotics were administered and blood and microdialysis samples were taken while the piglets were awake and free moving in their pen. Results In five of the six piglets the microdialysis catheter remained functional until the end of the fourth sampling day. In one piglet, the probe membrane broke on day 2 after intense struggling of the piglet during blood sampling. No adverse events (bleeding, infection, pain or other discomfort) were observed during the placement of the microdialysis catheter and whole study period. Conclusion This study shows that it is feasible to use microdialysis to study tissue drug disposition in free moving piglets over multiple days, adding to the potential of the juvenile pig in pediatric drug research.

Publication year:2021