Tissue on chip (TOC) have been developed to permit the study of human physiology in a tissue-specific context, to enable development of novel in vitro disease models, and to potentially serve as replacements of animals in drug development and toxics testing. Here we developed an innovative gut-liver-on-chip system useful to predict oral drug administration and first pass metabolism. Liver and intestine are the two main organs involved in the first pass metabolism. First-pass effects consist mainly in the reduction of bioavailability of drugs and xenobiotics. The prediction of this mechanism is important both for the development of new substances, but also for toxicity testing. For this purpose, we designed a microfluidic device, which interconnect 3D human intestinal equivalent (3D-HIE) and HepG2-microtissues, recapitulating, as proof of principle, the intestinal and hepatic first-pass effect mechanism of ethanol. 3D …