Tolerance to iotrolan after subarachnoid injection in animals.

Neural tolerance after intracisternal administration of iotrolan was compared with that after iohexol, iopamidol, and metrizamide in mice, rats, and guinea pigs. Around the level of the ED50 (approximately two to four times the human dose) tolerance to iotrolan appeared to be much better than tolerance to the other agents. A study in rabbits comparing iotrolan with iohexol produced approximately the same result. High doses of iotrolan, iohexol, and iopamidol were almost equally well tolerated by rats, as were iotrolan and iohexol by rabbits. Tolerance to metrizamide by rats and to iopamidol by guinea pigs was vastly inferior. In support of this very good general tolerance histologic examinations of the spinal tract and of the brain did not reveal any substance-related changes in beagles after lumbar administration of a high dose. An investigation in rats using mannitol and sorbitol formulations with differing osmotic pressures indicates that contrast tolerance is influenced primarily by the chemotoxicity and not by increased osmotic pressure. As shown by the results of the preclinical investigations, iotrolan should be ideal for use in myelography and also appears highly suitable for the examination of other body cavities.