Utilizing bile acid carrier mechanisms to enhance liver and small intestine absorption.

On the basis of the enterohepatocycling phenomenon of bile acids involving the intestines, liver, and gallbladder, it was conceptualized that bile acids could serve as a molecular carrier of drugs by taking advantage of the bile acid active transport mechanism. It was further proposed that derivatization or analogation of bile acids at the C3-OH position was the desired route because of the reactive hydroxyl group and, moreover, because of the active transport requirement of retaining the C17 side chain with a single terminal acidic function. Using 3-tosylcholic, 3-benzoylcholic, and 3-iodocholic acids, in situ liver absorption, biliary excretion, and intestinal absorption studies in the rat were successful in establishing the concept that C3-derivatives and analogs of bile acids are, potentially, novel molecular delivery systems for intestinal and liver-site directed absorption.