Absorption, distribution, metabolism and excretion of glucosamine sulfate - A review

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 C-14 labeled Gl (C-14-Gl) administer ed with 502 mg CGS indicate that the disappearance of Gl is due to an incor poration into the plasma globulins that occurs with a lag time of 0.45 h an d a rate of 0.26 h(-1). The radioactivity reaches a peak after 10 h and is eliminated with a t(1/2) of 95 h. After single i.v. doses of 502 mg CGS tra ced with C-14-Gl, the urinary excretion in 120 h accounted for 29 % of the administered dose. Consistent results are obtained in rat and dogs, in whic h radioactivity rapidly appears in liver, kidneys and other tissues, includ ing 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 adm inistered dose, mostly in the first 8 h after administration. Similar resul ts were obtained tracing CGS with C-14-Gl. Consistent results of urinary ex cretion were obtained in rats and dogs tracing CGS with C-14-Gl. The excret ion of radioactivity in feces was small. The elimination of radioactivity with the expired air as (CO2)-C-14 measure d in rats amounted to 49 % of the administered dose in the 144 h following the administration, 16 % of which occured in the first 6 h. Intramuscular administration of CGS In man, a single intramuscular injection of 502 mg CGS traced with C-14-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 mug/ml) of the ion exchange chromatography method. After a single dose of 314 mg CGS traced with C-14-Gl, radioactivity appeared in corporated 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 administrati on. The radioactivity then was eliminated with a t(1/2) of 58 h. The absolu te oral bioavailability evaluated on the AUCs of the globulin-incorporated radioactivity was 44 %. The fecal excretion in 120 h was 11.3 % of the admi nistered dose showing that at least 88.7 % of the administered dose was abs orbed through the gastrointestinal tract. The difference of 45 % is probabl y due to a hepatic first-pass effect. Investigated in the rat with doses fr om 126 to 3768 mg CGS traced with C-14-Gl, a linear relationship was found with the AUCs as well as between doses and the C-max of radioactivity in to tal 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, occuring mostly in the first 8 h after administratio n. After administration of 1884 mg repeated for 7 days the daily urinary ex cretion 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 allowe d to conclude that daily 1884 CGS administered either t.i.d. in sugar coate d tablets or once a day in oral solution were bioequivalent. The elimination of radioactivity with the expired as (CO2)-C-14 measured in rats was 82 % of the administered dose in the 144 h following the administ ration, 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 orall y C-14 uniformly labeled glucose. The kinetic in plasma and the tissue dist ribution of glucose differed totally from those of Gl, pointing out that ex ogenous glucose provides the energy for biochemical processes, whereas exog enous Gl acts mainly as substrate for the biosynthesis of mucopolysaccharid es and of biopolymers of the articulations and bones. There was no evidence of interaction by Gl orally administered with the ADME of glucose.