Synovial fluid levels and serum pharmacokinetics in a large animal model following treatment with oral glucosamine at clinically relevant doses

• Published in: Arthritis and rheumatism 2005-01, Vol.52 (1), p.181-191
• Main Authors: Laverty, Sheila, Sandy, John D., Celeste, Christophe, Vachon, Pascal, Marier, Jean‐Francois, Plaas, Anna H. K.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Dose-Response Relationship, Drug; Electrophoresis - methods; Electrophoresis - standards; Female; Glucosamine - administration & dosage; Glucosamine - blood; Glucosamine - pharmacokinetics; Horses; Injections, Intravenous; Intubation, Gastrointestinal; Medical sciences; Osmolar Concentration; Pharmacology. Drug treatments; Synovial Fluid - metabolism
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.20762

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 ∼300 μM (∼50 μg/ml) following IV dosing and ∼6 μM (∼1 μg/ml) following NG dosing. Synovial fluid concentrations reached 9–15 μM with IV dosing and 0.3–0.7 μM with NG dosing, and remained elevated (range 0.1–0.7 μM) in most animals even at 12 hours after dosing. Following NG dosing, the median serum maximal concentration of 6.1 μM (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. Conclusion 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.