NEURAL TOLERABILITY OF IODIXANOL IN MICE AND DOGS AFTER SINGLE AND REPEATED INTRACISTERNAL ADMINISTRATION

The neural tolerability of iodixanol has been assessed in studies in m ice and dogs. The animals received up to 4 injections in the cisterna cerebellomedullaris while under light anesthesia. Iotrolan was include d as a reference substance in 1 study. The observations comprised asse ssment of clinical behavior, cerebrospinal fluid analysis, hematology, clinical chemistry and/or macroscopic and microscopic examination at necropsy. In addition, the repeated-dose dog study, urinalysis and oph thalmoscopy were performed, electrocardiograms obtained, and respirato ry rate, blood pressure and rectal temperature measured. Clinical sign s and minor pathological changes caused by the injection procedures we re seen in all studies in some animals treated with iodixanol as well as in control animals. Single (2.0 g I/kg) and repeated (0.960 g I/kg) intracisternal administration of iodixanol to mice caused no signific ant toxicological effects. Two dogs treated with a high dose of iodixa nol (0.256 g I/kg; 0.8 ml/kg) had pathological changes (meningeal infl ammation and/or necrosis) that were more severe than those observed in control dogs. Single and repeated intracisternal administration of 0. 128 g I/kg (0.4 ml/kg) of iodixanol to dogs, however, caused no signif icant toxicological effects. Apart from the findings in the 2 dogs, th e neurological and neuropathological changes elicited by iodixanol wer e similar to those induced by control or reference substances. The res ults from these intracisternal toxicity studies in mice and dogs indic ate a significant margin of safety regarding the use of iodixanol in c linical intra-thecal indications.