title: The human pharmacokinetics of oral ingestion of glucosamine and chondroitin sulfate taken separately or in combination.
abstract: 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 (GlcN) and chondroitin sulfate (CS) when taken separately or in combination as a single dose in normal individuals (n=29) and (2) the PK of GlcN and CS when taken as a single dose after 3 months daily dosing with GlcN, CS or GlcN+CS, in patients with symptomatic knee pain (n=28).
  
  
  METHODS
  The concentration of GlcN 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 microg/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 GlcN. On the other hand, the Cmax (single-dose study) and AUC values (multiple-dose study) for ingested GlcN were significantly reduced by combination dosing with CS, relative to GlcN dosing alone.
  
  
  CONCLUSIONS
  We conclude that pain relief perceived following ingestion of CS probably does not depend on simultaneous or prior intake of GlcN. 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 GlcN with CS was found to reduce the plasma levels seen with GlcN dosing alone, any improved pain relief by combination dosing cannot be explained by higher circulating concentrations of GlcN.
authors.affiliation: University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Jackson
authors.forename: A H
authors.initials: AH
authors.lastname: Plaas
authors.forename: J D
authors.initials: JD
authors.lastname: Sandy
authors.forename: C
authors.initials: C
authors.lastname: Hua
authors.forename: S
authors.initials: S
authors.lastname: Kim-Rolands
authors.forename: J G
authors.initials: JG
authors.lastname: Barnhill
authors.forename: C L
authors.initials: CL
authors.lastname: Harris
authors.forename: D O
authors.initials: DO
authors.lastname: Clegg
mesh_terms: D000284:Administration, Oral; D000328:Adult; D018771:Arthralgia / Q000378:metabolism*; D002809:Chondroitin Sulfates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005944:Glucosamine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy*; D010147:Pain Measurement; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D002809:Chondroitin Sulfates; D005944:Glucosamine