Pharmacokinetic profile that reduces nephrotoxicity of gentamicin in a perfused kidney-on-a-chip

9^th International Conference on Dialysis and Renal Care

August 18-19, 2016 London, UK

Sejoong Kim

Seoul National University Bundang Hospital, Republic of Korea

Posters & Accepted Abstracts: J Nephrol Ther

Abstract :

Nephrotoxicity is often underestimated because renal clearance in animals is higher compared to in humans. This study aims to illustrate the potential to fill in such pharmacokinetic gaps between animals and humans using a microfluidic kidney model. As an initial demonstration, we compare nephrotoxicity of a drug, administered at the same total dosage, but using different pharmacokinetic regimens. Kidney epithelial cell, cultured under physiological shear stress conditions, are exposed to gentamicin using regimens that mimic the pharmacokinetics of bolus injection or continuous infusion in humans. The perfusion culture utilized is important both for controlling drug exposure and for providing cells with physiological shear stress (1.0 dyn/cm2). We tested two drug treatment regimens that give the same gentamycin dose over a 24 hour period. The bolus injection-mimicking regimen also led to less cytotoxicity and allowed the epithelium to maintain low permeability, while continuous infusion led to an increase in cytotoxicity and permeability. These data show that gentamicin disrupts cell-cell junctions, increases membrane permeability, and decreases cell viability particularly with prolonged low-level exposure. Importantly a bolus injection-mimicking regimen alleviates much of the nephrotoxicity compared to the continuous infused regimen. In addition to potential relevance to clinical gentamicin administration regimens, the results are important in demonstrating the general potential of using microfluidic cell culture models for pharmacokinetics and toxicity studies.

Biography :

Email: sejoong2@gmail.com