CONCENTRATIONS OF CYCLOSPORINE-A AND ITS METABOLITES IN HUMAN TISSUES POSTMORTEM

We report concentrations and distribution of cyclosporine A (CsA) and individual metabolites associated with various organ tissues and whole-blood specimens collected at autopsy from seven transplant patients who received CsA therapy. Solid-phase extraction (SPE) and specific high-performance liquid chromatographic (HPLC) procedures were used to separate and quantitate the cyclosporines. Patterns of deposition were unique for the various tissue types. Metabolites M17, M1, M18, and M8 (in addition to CsA) were the principal compounds detected in significant quantities. On a per weight basis, the sum concentration of CsA and metabolites in organ tissues was up to 53 times greater than in companion whole-blood specimens. Metabolite M17 prevailed in most tissues, except in fat and pancreas, where CsA was predominant. Overall, pancreas specimens contained a greater concentration of cyclosporines (per kilogram of tissue), followed consecutively by spleen, liver, fat, kidney, lung, bone marrow, heart, and whole blood. No CsA-related compounds were detected in brain or spinal cord tissue.