[Animal experimental testing of injection solutions for intra-arterial tolerability]

Severe damage, even necrosis, has been noted in the past in man after accidental intra-arterial (i.a.) application of injectable preparations intended for intravenous (i.v.) or other parenteral administration. Various experimental models in animals have been developed to test an eventual i.a. incompatibility. Reasons are given for the methodology used by us in the central artery of the rabbit's ear with and without occlusion (harder and softer test variant). Herewith preparations of acetamidoeugenol and thiopental were tested to work out an appropriate measure. In comparison we investigated a series of "placebo solutions" with solvents or other excipients used in the formulation of injection solutions. The "placebos" investigated were then classified with regard to their i.a. compatibility, because in many cases an intra-arterial intolerance can be attributed to them as much as to the active principle. The choice of experimental animal model, the transferability of results to man as well as possible mechanisms taking place in an accidental i.a. application and in the development of ensuing damage are discussed.