Physiologic pharmacokinetic model of iopanoic acid metabolism in rats.

The kinetics of iopanoate metabolism have been examined using a physiologic and pharmacokinetic model in rats. The kinetics of iopanoic acid concentration in blood and in eight other major tissue distribution compartments have been determined and fitted to computer-generated concentrations based on a well-established pharmacokinetic model. The results of these studies in nonfasted, conscious rats revealed that after gastric administration of the contrast material tissue concentrations never exceed 30 microgram/g even in the liver. In addition, a clear-cut enterohepatic circulation of the drug was noted in the experimental setting and had to be incorporated into a computer-generated model to account for differences in the predicted model as compared to the experimental data. Such data point out the importance of knowledge of pharmacokinetics of a drug for development of more appropriate dosage regimens of older compounds, theoretical design and testing of new compounds, or to explain clinically observed drug-related phenomenon.

Gastrointestinal radiology. A study of iopanoate metabolism and toxicity in isolated cell cultures.

Radiologists are familiar with certain toxic manifestations of biliary and urinary contrast media (ie, acute tubular necrosis in dehydrated patients with diabetes or multiple myeloma), and with the specific effects of contrast media on other diagnostic tests (ie, I uptake, PBI, etc). These have been studied because of their clinical and diagnostic impact upon patient management. It has become apparent that many subtle, though perhaps predictable, drug interactions occur. Some of these are of obvious clinical and therapeutic significance and have been studied and described in detail. The authors have tried to establish the effects of clinically used drugs on the contrast medium iopanoic acid. The fact that both drugs thus far studied - aspirin and cholestyramine - have profound laboratory effects on iopanoic acid suggests that some systematic approach to the study of the clinical pharmacology of contrast agents is desirable. Others have also observed effects of contrast media on various clinical and laboratory parameters, but most observations are isolated empirical observations, and our basic understanding of the mechanisms involved are crude at best. How might this problem be approached? Although in vivo pharmacokinetic studies in unanesthetized animals allow identification of possible drug-drug interactions in the absence of multiple clinical variables and let us do crossover studies with each animal acting as its own control, such studies are difficult, expensive, and do little to establish the mechanism of the interaction. The authors are currently approaching this problem with a more basic technique. In conjunction with colleagues in gastroenterology and pharmacy, they are studying iopanoate metabolism and aspirin-iopanoate interaction in isolated hepatocyte monolayer cultures. The preliminary data from these experiments will be presented, and the significance of these results and the potential usefulness of this model will be discussed.