A Gut–Liver–Kidney (GLK) Multi-Organ Chip for Physiologically Modeling the Renal Filtration and Reabsorption of Oral Drugs
摘要
Orally administered drugs undergo a complex process of absorption-distribution-metabolism-excretion (ADME), passing through the gut, liver, and kidney. Studying the ADME process of drugs can help predict the drug’s safety and pharmacokinetic properties. Orally administered drugs are absorbed in the gut and metabolized in the liver, and eliminated mostly through the kidney, where drugs are first filtered in the glomeruli and selectively reabsorbed in the tubules. Previously, we showed that a gut-liver chip can reproduce the dynamic and continuous process of gut absorption and liver metabolism. Here, a multi-organ system, Gut-Liver-Kidney (GLK) chip, integrating the main functions of the gut, liver, and size-selective renal filtration with physiologically realistic fluidic connection was developed to reproduce the ADME of orally administered drugs. We confirmed that the filtration and the reabsorption of model drug was reproduced in our GLK chip, mimicking the fate of drugs in the body. Our GLK chip can be a useful in vitro model system for studying the continuous process of ADME and consequent pharmacokinetics (PK) properties of oral drugs.