The pathophysiology of Sandimmune (cyclosporine) in man and animals.

Part II: The side-effects of Sandimmune that have also been observed clinically include hepatic dysfunction, glucose intolerance, thrombo-embolic complications and nervous system disorders. To determine the cause and significance of such effects, the actions of Sandimmune on the liver, the pancreas, on hematostasis and the nervous system were examined. Comparisons were made between animal and human data obtained in vivo and in vitro, and the clinical setting under which the side-effects occur was analyzed. The actions of Sandimmune on the liver seem to reflect mostly a cholestasis with a small depression in protein synthesis and a mild disturbance in lipid metabolism of uncertain origin. The action of Sandimmune on the pancreas suggests insulin resistance and possibly a secretory disturbance, with no evidence for depressed insulin synthesis, except in animals at high doses. Sandimmune does not seem to promote thromboembolism in man, although fibrinolysis may be depressed and platelet aggregation can be enhanced. The effects of Sandimmune on the nervous system are unclear, for tremor is common but of uncertain origin, whereas seizures and encephalopathy are rare and invariably associated with other risk factors.