COMPARISON OF DIFFERENT ASSAYS FOR THE QUANTITATION OF FK-506 LEVELS IN BLOOD OR PLASMA

In a prospective study, we evaluated the analytical performance of dif ferent assays for the quantitation of FK 506 in blood and plasma. The new whole blood IMX assay was compared with four modifications (liquid /liquid or solid/liquid extraction of blood or plasma respectively) of the standard enzyme-linked immunosorbent assay (ELISA). Both assays u tilize the same monoclonal antibody for detection of FK 506. Using iso lated FK 506 metabolites generated in vitro, this antibody was shown t o recognize not only the unmodified parent drug but also FK 506 metabo lites. In stable liver-grafted patients, sensitivity of both modificat ions of the whole blood ELISA was adequate. In contrast, in some stabl e patients, plasma ELISA was not able to detect FK 506; this was obser ved mainly after liquid/liquid extraction of FK 506. Sensitivity of th e IMX assay was also low; in six of 10 stable liver-grafted patients, IMX levels were below the limit of detection. In all assays, FK 506 le vels were found to be elevated during episodes of liver dysfunction; a possible explanation for this effect would be that of accumulation of cross-reacting FK 506 metabolites. As FK 506 metabolites are known to be less immunosuppressive than the parent drug, liver function should always be taken into account if IMX or ELISA levels are used for drug monitoring.