Development of nonionic contrast media.

In this brief history, the author reviews the observations that led to his developing a nonionic contrast medium. Current knowledge suggested that if a water-soluble medium could be made isotonic to human plasma, it would cause less pain and toxicity than the ionic media then in use. The principles and design of such a medium are discussed, as well as the subsequent chemical development and testing in animal models of first generation (metrizamide) and second generation (iohexol) nonionic media. Iohexol, which is described as a nonionic, monomeric ratio 3 contrast medium, was selected for clinical testing from among competing substances due to its low toxicity in a number of animal models. The results from these experimental models predicted that iohexol would cause fewer and less severe adverse reactions in clinical use than ionic ratio 1.5 media.