Pharmacokinetics of Glutathione-Dextran Macromolecular Conjugate in Mice.

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Abstract
A fluorescein-labeled dextran-glutathione conjugate (FD-GSH) was synthesized in order to examine its disposition in the body. GSH was covalently attached to the FITC-labeled dextran by the cyanogen bromide activation method. Mice were injected with FD-GSH through the tail vein, and the levels of FD-GSH in the blood and various organs were measured fluorometrically. A substantial level of FD-GSH was found in the liver and this reached a maximum at 6-8 h after the injection. The hepatic uptake clearance was estimated to be 0.541 +/- 0.014 ml/h/g tissue or 42.4 +/- 9.8 ml/h/kg body weight. FD--GSH accumulated in the liver for a long period, while the half-life of the conjugate in the blood circulation was 1.45h. The cumulative urinary and fecal excretions of FD-GSH were 14% and 4% of dose at 72h after the injection, respectively. A molecular design of the conjugate was discussed on the basis of the results.

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