Y Tokunaga1, A M Alak. 1. Pharmaceutical and Pharmacokinetic Research Laboratories Fujisawa Pharmaceutical Company, Ltd. Osaka, Japan.
Abstract
PURPOSE: To determine the concentrations of FK506 and its metabolites in blood from liver transplant patients and subjects with hepatic dysfunction. METHODS: HPLC was combined with an enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of FK506 and its immunoreactive metabolites in human whole blood. RESULTS: In four liver transplant patient, most of the immunoreactivity was seen in the HPLC fractions where unchanged FK506 eluted. FK506 accounted for about 95% or more of the total immunoreactivity in the first days of posttransplant. Immunoreactivity observed in the nonFK506 fractions ranged from 1.6% to 10.7% of the total immunoreactivity; about 30% of the nonFK506 immunoreactivity was due to M-III(15-O-demethyl FK506). Blood from subjects 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 immunoreactivity was recovered in the FK506 fraction. M-III was detected in the blood 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.
PURPOSE: To determine the concentrations of FK506 and its metabolites in blood from liver transplant patients and subjects with hepatic dysfunction. METHODS: HPLC was combined with an enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of FK506 and its immunoreactive metabolites in human whole blood. RESULTS: In four liver transplant patient, most of the immunoreactivity was seen in the HPLC fractions where unchanged FK506 eluted. FK506 accounted for about 95% or more of the total immunoreactivity in the first days of posttransplant. Immunoreactivity observed in the nonFK506 fractions ranged from 1.6% to 10.7% of the total immunoreactivity; about 30% of the nonFK506 immunoreactivity was due to M-III(15-O-demethyl FK506). Blood from subjects 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 immunoreactivity was recovered in the FK506 fraction. M-III was detected in the blood 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.
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