Abstract: The present disclosure relates to novel microfluidic devices and their use for operating microphysiological systems. The novel microfluidic devices are particularly useful for pharmacokinetic-pharmacodynamic analysis in the context of ADME(T) profiling. The present disclosure provides novel microfluidic devices comprising a first “blood” circuit with one or more cell culture compartments, and a second “urine” circuit comprising a renal filtration and reabsorption unit, wherein both circuits are connected with each other via the filtration unit and the reabsorption unit. The present disclosure further provides methods, kits and assays implementing the novel microfluidic devices.