title: Synovial fluid levels and serum pharmacokinetics in a large animal model following treatment with oral glucosamine at clinically relevant doses.
abstract: OBJECTIVE
  To examine the concentration of glucosamine in the synovial fluid and its pharmacokinetics in serum in a large animal model following dosing with glucosamine HCl at clinically relevant levels.
  
  
  METHODS
  Eight adult female horses were studied. After an overnight fast, glucosamine HCl (20 mg/kg of body weight) was administered by either nasogastric (NG) intubation or intravenous (IV) injection. Blood samples were collected before dosing and at 5, 15, 30, 60, 120, 180, 240, 360, 480, and 720 minutes after dosing. Synovial fluid samples were collected from the radiocarpal joints 48 hours before dosing and at 1 and 12 hours after dosing. Glucosamine was assayed by fluorophore-assisted carbohydrate electrophoresis.
  
  
  RESULTS
  The maximum concentration of glucosamine in serum reached approximately 300 muM ( approximately 50 microg/ml) following IV dosing and approximately 6 microM (approximately 1 microg/ml) following NG dosing. Synovial fluid concentrations reached 9-15 microM with IV dosing and 0.3-0.7 microM with NG dosing, and remained elevated (range 0.1-0.7 microM) in most animals even at 12 hours after dosing. Following NG dosing, the median serum maximal concentration of 6.1 microM (range 4.38-7.58) was attained between 30 minutes and 4 hours postdose. The mean apparent volume of distribution was 15.4 liters/kg, the mean bioavailability was 5.9%, and the mean elimination half-life was 2.82 hours.
  
  
  CONCLUSIONS
  Clinically relevant dosing of glucosamine HCl in this large monogastric animal model results in serum and synovial fluid concentrations that are at least 500-fold lower than those reported to modify chondrocyte anabolic and catabolic activities in tissue and cell culture experiments. We conclude that the apparent therapeutic benefit of dietary glucosamine on pain and joint space width in humans and animals may be secondary to its effects on nonarticular tissues, such as the intestinal lining, liver, or kidney, since these may be exposed to much high levels of glucosamine following ingestion.
authors.affiliation: Faculté de Médicine Vétérinaire, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Sheila
authors.initials: S
authors.lastname: Laverty
authors.forename: John D
authors.initials: JD
authors.lastname: Sandy
authors.forename: Christophe
authors.initials: C
authors.lastname: Celeste
authors.forename: Pascal
authors.initials: P
authors.lastname: Vachon
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Marier
authors.forename: Anna H K
authors.initials: AH
authors.lastname: Plaas
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004586:Electrophoresis / Q000379:methods / Q000592:standards; D005260:Female; D005944:Glucosamine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006736:Horses; D007275:Injections, Intravenous; D007441:Intubation, Gastrointestinal; D009994:Osmolar Concentration; D013582:Synovial Fluid / Q000378:metabolism*
chemical_list: D005944:Glucosamine