Organ perfusion techniques in drug development

This review focuses on the utility of in situ organ perfusion techniques in the drug development process. Using illustrative examples throughout, studies undertaken in the major systems responsible for absorption, metabolism, and excretion, namely the intestine, liver and kidney, are described. These studies demonstrate the use of lumen only and lumen and vascular methods of intestinal perfusion to examine issues such as extent of absorption, mechanisms of absorption, and intestinal metabolism. In the liver, four different modes are examined single-pass, impulse-response, infusion-washout, and recirculating. Studies cited show the value of liver perfusions in the estimation of hepatic clearance, metabolism, drug-drug interactions, evaluation of membrane transport, biliary extraction, and the effect of protein binding. The last perfused organ system detailed is the kidney, which is discussed with examples demonstrating estimation of renal clearance, the mechanism of clearance and associated transport systems, and the role of renal metabolism. The potential application of these techniques to the drug development process is discussed.