Pharmacokinetics of Glutathione-Dextran Macromolecular Conjugate in Mice

• Published in: Biological & pharmaceutical bulletin Vol. 18; no. 11; pp. 1544 - 1547
• Main Authors: KANEO, Yoshiharu, UEMURA, Tomochika, TANAKA, Tetsuro, KANOH, Satoshi, MATSUOKA, Aya
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1995; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; Biological and medical sciences; conjugate; cyanogen bromide; dextran; Dextrans - administration & dosage; Dextrans - pharmacokinetics; Feces - chemistry; fluorescein; Fluorescein-5-isothiocyanate; Fluoresceins; General pharmacology; glutathione; Glutathione - administration & dosage; Glutathione - pharmacokinetics; Half-Life; Injections, Intravenous; Kidney - metabolism; Liver - metabolism; Male; Medical sciences; Mice; Mice, Inbred Strains; mouse; pharmacokinetics; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Tissue Distribution; Thiol; Intravenous administration; Control release polymer; Liver; Rodentia; Tripeptide; Drug carrier; Normal; Dextran; Vertebrata; Mammalia; Mouse; Animal; Distribution; Covalent bond; Oside polymer; Conjugation; Chemical uptake; Antidote; Fluorescent compound; Pharmacokinetics; Labelled compound; Glutathione
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.18.1544

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 6-8h 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.