EFFECT OF CYCLOSPORINE-A ON THE DEMETHYLATION OF AMINOPYRINE IN RATS IN-VIVO

Serial determinations of hepatic function by quantitative tests might provide clinically useful information following liver transplantation provided that the test result is not influenced by the immunosuppressive regimen. To investigate the effect of cyclosporine A with and without prednisolone on established quantitative tests of hepatic function, rats were fed cyclosporine A at a dose resulting in average through blood levels of 1,176 ng/ml, and the aminopyrine breath test which reflects microsomal function, the decarboxylation of ketoisocaproic acid which reflects mitochondrial function and the galactose breath test which reflects cytosolic function were performed at intervals. Cyclosporine A did not impair the demethylation of aminopyrine and the decarboxylation of ketoisocaproic acid in vivo. The metabolism of galactose was enhanced by 25%. The results indicate that in contrast to in vitro experiments, where cyclosporine A has been shown to markedly inhibit the demethylation of aminopyrine and to result in a decrease of cytochrome P-450, therapeutic concentrations of cyclosporine A and prednisolone do not impair aminopyrine demethylation in vivo. Thus, the aminopyrine breath test is a reliable index of hepatic function also in the presence of immunosuppressive treatment.