Theoretic and experimental aspects of regional liver infusion

Pharmacokinetic theory of hepatic arterial infusion chemotherapy predicts that parameters, such as hepatic blood flow, hepatic drug extraction, and extrahepatic drug clearance, may potentially be manipulated to enhance the selectivity of hepatic artery drug administration. In practice, diminution of hepatic blood flow through the use of degradable starch microspheres or gelatin sponge embolization has been accomplished and has improved drug selectivity. Likewise, augmentation of hepatic drug extraction improves the pharmacokinetic advantages of regional chemotherapy for liver tumors. Development of optimal hepatic infusion chemotherapy approaches can be undertaken rationally and in an expeditious fashion by applying pharmacokinetic principles to create innovative treatment regimens and by testing them in preclinical and phase I investigations.