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

We illustrated the potential to fill in pharmacokinetic gaps between animals and humans using a microfluidic kidney model. We compare nephrotoxicity of gentamicin, administered at the same total dosage, but using two different 24-hour 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. The bolus injection regimen attenuated epithelial barrier dysfunction and cytotoxicity more than continuous infusion regimen. Importantly, the results demonstrated the general potential of using microfluidic cell culture models for pharmacokinetics and toxicity studies.