FK506 (TACROLIMUS) AND ITS IMMUNOREACTIVE METABOLITES IN WHOLE-BLOOD OF LIVER-TRANSPLANT PATIENTS AND SUBJECTS WITH MILD HEPATIC-DYSFUNCTION

Purpose. To determine the concentrations of FK506 and its metabolites in blood from liver transplant patients and subjects with hepatic dysf unction. Methods. HPLC was combined with an enzyme-linked immunosorben t assay (ELISA) to determine the concentrations of FK506 and its immun oreactive metabolites in human whole blood. Results. In four liver tra nsplant patients, most of the immunoreactivity was seen in the HPLC fr actions where unchanged FK506 eluted. FK506 accounted for about 95% or more of the total immunoreactivity in the first days posttransplant. Immunoreactivity observed in the nonFK506 fractions ranged from 1.6% t o 10.7% of the total immunoreactivity; about 30% of the nonFK506 immun oreactivity was due to M-III (15-O-demethyl FK506). Blood from subject s with mild hepatic dysfunction was examined at 1.5 and 6 hours after an oral and intravenous dose, respectively, by HPLC-ELISA. Regardless of the route of administration, more than 96% of the total immunoreact ivity was recovered in the FK506 fraction. M-III was detected in the b lood of 3 of 6 subjects after an oral dose, but in none of these after an intravenous dose. Conclusions. ELISA is an appropriate method for therapeutic drug monitoring of FK506.