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NEUROTOXICITY OF X-RAY CONTRAST MEDIA

RELATION TO LIPID SOLUBILITY AND BLOOD-BRAIN BARRIER PERMEABILITY

STANLEY I. RAPOPORT M.D. and HERBERT LEVITAN PH.D.

Neurotoxicity of x-ray contrast media used in cerebral and spinal cord angiography is related to 2 factors.

The specific factor is the lipid solubility, or octanol/water partition coefficient of the contrast medium anion, which determines its passage through membranes of cerebrovascular endothelial cells of the blood-brain barrier.

The nonspecific factor is solution osmolality, which opens tight junctions between the cells through which the contrast media then can enter the brain.

Differences in neurotoxicity of 8 contrast media that are derivatives of benzoic acid are correlated with differences in their specific octanol/water partition coefficient. Brain uptake depends on the partition coefficient and on pKa, which determines the proportion of dissociated and undissociated form of the acid in blood. Systemic LD50 of the benzoic acid derivates also depends on octanol/water partition and on pKa.


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