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Home / Equine Research Bank / Arthritis Rheum / Synovial fluid levels and serum pharmacokinetics in a large ...
Arthritis and rheumatism2005; 52(1); 181-191; doi: 10.1002/art.20762

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

Abstract: 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.
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Publication Date: 2005-01-11 PubMed ID: 15641100DOI: 10.1002/art.20762Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.
  • Validation Study

Summary

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This research article focuses on a study conducted on large female horses to understand the concentration of a compound called glucosamine in their synovial fluid and blood serum. The study measured the levels of glucosamine after the animals were administered with glucosamine HCl and found that the resulting glucosamine concentrations were significantly lower than the levels previously reported to affect cartilage cell activities in lab-based studies.

Study Design

  • The study participants were eight adult female horses.
  • These animals were given a dosage of Glucosamine HCl (20 mg/kg of body weight) after fasting overnight.
  • The drug was administered either through nasogastric (NG) intubation or intravenous (IV) injection.
  • Blood samples and Synovial fluid (fluid found in joints) were collected at specified intervals before and post-administration.
  • Glucosamine levels were measured using a technique called fluorophore-assisted carbohydrate electrophoresis.

Findings

  • Post IV dosing, the maximum glucosamine concentration in the blood serum reached about 50 micrograms/ml (300 muM).
  • Post NG dosing, the maximum glucosamine concentration in the blood serum was only about 1 microgram/ml (6 muM).
  • Glucosamine concentrations in Synovial fluid reached between 9-15 microM with IV dosing and 0.3-0.7 microM with NG dosing.
  • Glucosamine levels remained slightly elevated in most animals even 12 hours after the dosage.
  • The mean bioavailability (how much of the drug your body can actually use) was 5.9%.
  • The mean elimination half-life (the time it takes for half of the drug to be eliminated from your body) was 2.82 hours.

Conclusions

  • The resulting concentrations of glucosamine, after clinically relevant dosing in this large animal model, were at least 500 times lower than those previously reported to affect the activities of cartilage cells in lab experiments.
  • This led the researchers to suggest that the observed therapeutic benefits of dietary glucosamine on pain and joint space width might be due to its effect on nonarticular tissues, such as the intestinal lining, liver, or kidney, which may be exposed to higher levels of glucosamine following ingestion.

Cite This Article

APA
Laverty S, Sandy JD, Celeste C, Vachon P, Marier JF, Plaas AH. (2005). Synovial fluid levels and serum pharmacokinetics in a large animal model following treatment with oral glucosamine at clinically relevant doses. Arthritis Rheum, 52(1), 181-191. https://doi.org/10.1002/art.20762

Publication

Arthritis and rheumatism
ISSN: 0004-3591
NlmUniqueID: 0370605
Country: United States
Language: English
Volume: 52
Issue: 1
Pages: 181-191

Researcher Affiliations

Laverty, Sheila
  • Faculté de Médicine Vétérinaire, Université de Montréal, Montreal, Q, Canada.
Sandy, John D
    Celeste, Christophe
      Vachon, Pascal
        Marier, Jean-Francois
          Plaas, Anna H K

            MeSH Terms

            • Administration, Oral
            • Animals
            • Dose-Response Relationship, Drug
            • Electrophoresis / methods
            • Electrophoresis / standards
            • Female
            • Glucosamine / administration & dosage
            • Glucosamine / blood
            • Glucosamine / pharmacokinetics
            • Horses
            • Injections, Intravenous
            • Intubation, Gastrointestinal
            • Osmolar Concentration
            • Synovial Fluid / metabolism

            Citations

            This article has been cited 24 times.
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