Drug interaction between cyclosporin A and nizatidine in Sprague-Dawley rats

The H2-receptor antagonists seem to be effective in prevention and treatment of stress ulcer in transplant recipients. In a previous study on rats, an increase was observed in cyclosporinaemia and hepatotoxicity after administration of cimetidine or ranitidine in association with cyclosporin A (CyA). On the contrary, famotidine does not influence the blood CyA levels. The aim of the study was to detect the possible synergistic nephro- and hepatotoxicity of nizatidine administered in association with CyA, assaying the serum creatinine, the ALT and AST levels, and histological features of thirty young male Sprague-Dawley rats, divided into 6 groups of five animals each. After 10 days, all the rats were sacrificed, their blood was collected to assay serum creatinine, ALT, AST and serum CyA levels: kidneys and livers were processed for light microscopy. The results obtained demonstrated that, while the level of creatinine was normal in each group, the average level of transaminase and the serum levels of CyA were significantly higher in the animals receiving the association of CyA and nizatidine. Furthermore, this group demonstrated a mild infiltrate of the liver characterized in some cases with eosinophilic polymorphonuclear cells. In light of the results obtained, it is probable that the increase of cyclosporinaemia is the consequence of an enhanced hepatotoxicity due to administration of CyA in association with nizatidine.