The human pharmacokinetics of oral ingestion of glucosamine and chondroitin sulfate taken separately or in combination

Objective: As part of the National Institutes of Health (NIH)-sponsored Glucosamine/Chondroitin sulfate Arthritis Intervention Trial (GAIT) our objective here was to examine (1) the pharmacokinetics (PK) of glucosamine (GIcN) and chondroitin sulfate (CS) when taken separately or in combination as a single dose in normal individuals (n = 29) and (2) the PK of GIcN and CS when taken as a single dose after 3 months daily dosing with GIcN, CS or GIcN + CS, in patients with symptomatic knee pain (n = 28). Methods: The concentration of GIcN in the circulation was determined by established fluorophore-assisted carbohydrate electrophoresis (FACE) methods. The hydrodynamic size and disaccharide composition of CS chains in the circulation and dosage samples was determined by Superose 6 chromatography and FACE. Results: We show that circulating levels of CS in human plasma are about 20 mu g/ml. Most significantly, the endogenous concentration and CS disaccharide composition were not detectably altered by ingestion of CS, when the CS was taken alone or in combination with GIcN. On the other hand, the Cmax (single-dose study) and AUC values (multiple-dose study) for ingested GIcN were significantly reduced by combination dosing with CS, relative to GIcN dosing alone. Conclusions: We conclude that pain relief perceived following ingestion of CS probably does not depend on simultaneous or prior intake of GIcN. Further, such effects on joint pain, if present, probably do not result from ingested CS reaching the joint space but may result from changes in cellular activities in the gut lining or in the liver, where concentrations of ingested CS, or its breakdown products, could be substantially elevated following oral ingestion. Moreover, since combined dosing of GIcN with CS was found to reduce the plasma levels seen with GIcN dosing alone, any improved pain relief by combination dosing cannot be explained by higher circulating concentrations of GIcN. (C) 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.