alexa Absorption, distribution, metabolism and excretion of glucosamine sulfate. A review.
Toxicology

Toxicology

Journal of Drug Metabolism & Toxicology

Author(s): Setnikar I, Rovati LC, Setnikar I, Rovati LC

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Abstract This article reviews the literature related to the absorption, distribution, metabolism and excretion (ADME) of glucosamine (Gl) in man and in animals after administration of crystalline glucosamine sulfate (CGS). Intravenous administration of CGS In man, after single bolus intravenous (i.v.) injection of 1005 mg CGS (628 mg Gl), the parent Gl disappears from plasma with an apparent half life of 1.11 h. Investigations with uniformly 14C labeled Gl (14C-Gl) administered with 502 mg CGS indicate that the disappearance of Gl is due to an incorporation into the plasma globulins that occurs with a lag time of 0.45 h and a rate of 0.26 h-1. The radioactivity reaches a peak after 10 h and is eliminated with a t1/2 of 95 h. After single i.v. doses of 502 mg CGS traced with 14C-Gl, the urinary excretion in 120 h accounted for 29\% of the administered dose. Consistent results are obtained in rat and dogs, in which radioactivity rapidly appears in liver, kidneys and other tissues, including the articular cartilage. In man, after i.v. bolus injection of 1005 mg CGS, the urinary excretion in 24 h of Gl determined with ion exchange chromatography was 38\% of the administered dose, mostly in the first 8 h after administration. Similar results were obtained tracing CGS with 14C-Gl. Consistent results of urinary excretion were obtained in rats and dogs tracing CGS with 14C-Gl. The excretion of radioactivity in feces was small. The elimination of radioactivity with the expired air as 14CO2 measured in rats amounted to 49\% of the administered dose in the 144 h following the administration, 16\% of which occurred in the first 6 h. Intramuscular administration of CGS In man, a single intramuscular injection of 502 mg CGS traced with 14C-Gl, gave results similar to those after i.v. administration. Oral administration of CGS In man, after a single dose of 7.5 g CGS, Gl in plasma was below the limit of quantitation (3 micrograms/ml) of the ion exchange chromatography method. After a single dose of 314 mg CGS traced with 14C-Gl, radioactivity appeared incorporated in plasma globulins with a lag time of 1.5 h and increasing with a rate of 0.24 h-1. The peak was reached at the 9th h after administration. The radioactivity then was eliminated with a t1/2 of 58 h. The absolute oral bioavailability evaluated on the AUCs of the globulin-incorporated radioactivity was 44\%. The fecal excretion in 120 h was 11.3\% of the administered dose showing that at least 88.7\% of the administered dose was absorbed through the gastrointestinal tract. The difference of 45\% is probably due to a hepatic first-pass effect. Investigated in the rat with doses from 126 to 3768 mg CGS traced with 14C-Gl, a linear relationship was found with the AUCs as well as between doses and the Cmax of radioactivity in total and in deproteinized plasma. The urinary elimination in man of the parent Gl in 24 h determined with ion exchange chromatography after a single dose of 7.5 g of CGS was 1.19\% of the administered dose, occurring mostly in the first 8 h after administration. After administration of 1884 mg repeated for 7 days the daily urinary excretion of Gl increased from 1.60\% of the daily dose during the first 24 h to 2.22\% of the daily dose in the last 24 h. The steady state was reached after the second day. The urinary excretion at steady state during repeated administration allowed to conclude that daily 1884 CGS administered either t.i.d. in sugar coated tablets or once a day in oral solution were bioequivalent. The elimination of radioactivity with the expired as 14CO2 measured in rats was 82\% of the administered dose in the 144 h following the administration, 61\% of which occur in the first 6 h. Interaction of Gl with the ADME of glucose The ADME of glucose was investigated in the rat administering i.v. or orally 14C uniformly labeled glucose. The kinetic in plasma and the tissue distribution of glucose differed totally from those of Gl, pointing out that exogenous glucose provides the energy for biochemical processes, whereas exogenous Gl acts mainly as substrate for the biosynthesis of mucopolysaccharides and of biopolymers of the articulations and bones. There was no evidence of interaction by Gl orally administered with the ADME of glucose. This article was published in Arzneimittelforschung and referenced in Journal of Drug Metabolism & Toxicology

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