Biopharmaceutical Factors Influencing the Intestinal Absorption of Iopanoic Acid

Failure of the gallbladder to attain diagnostic opacification on the first study occurs in 15 per cent of all patients undergoing cholecystography with iopanoic acid (Telepaque). One-third of these are found to be normal on a second study. This creates a clinical problem of considerable magnitude because it makes a repeat examination mandatory in each of these cases. There is radiologic evidence to indicate that impaired first-dose visualization of the gallbladder is due to poor intestinal absorption of the iopanoic acid. Therefore, to study some biopharmaceutical factors which could cause irregular absorption, in vitro solubility experiments and in vitro absorption studies in dogs were performed. The results show that iopanoic acid, as used clinically, dissolves very slowly and is only slightly soluble in water, and is poorly absorbed from the intestine in the absence of bile salts. Recently precipitated iopanoic acid, the material formed in the stomach by the action of gastlc acid on sodium iopanoate, is much more soluble in water, dissolves much more rapidly, and is readily absorbed. The solubility and rate of solution of iopanoic acid is greatly enhanced when bile salts are added to the solution. In this circumstance the absorption of iopanoic acid equals that of the recently precipitated form. The experiments suggest that irregular absorption of iopanoic acid may be due to variations in the concentration of bile salts in the intestinal lumen at the time the iopanoic acid enters the duodenum. This may be avoided by giving substances with the iopanoic acid which will empty the gallbladder. The rapid absorption of the recently precipitated form in dogs without dependence on bile salts conforms with clinical data indicating that the sodium salt is more regularly absorbed. If regular absorption of contrast material is the critical factor in producing consistently maximal gallbladder opacification, the use of a salt form of the cholecystopaques would be advantageous. Since sodium iopanoate is not supplied commercially in the United States, the use of sodium ipodate (Oragrafin) or sodium tyropanoate (Bilopaque) might reduce the number of repeat cholecystograms necessary in clinical practice.