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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 26 times.
            1. Kearney CM, Khatab S, van Buul GM, Plomp SGM, Korthagen NM, Labberté MC, Goodrich LR, Kisiday JD, Van Weeren PR, van Osch GJVM, Brama PAJ. Treatment Effects of Intra-Articular Allogenic Mesenchymal Stem Cell Secretome in an Equine Model of Joint Inflammation. Front Vet Sci 2022;9:907616.
              doi: 10.3389/fvets.2022.907616pubmed: 35812845google scholar: lookup
            2. Bendele AM, Neelagiri M, Neelagiri V, Sucholeiki I. Development of a selective matrix metalloproteinase 13 (MMP-13) inhibitor for the treatment of Osteoarthritis. Eur J Med Chem 2021 Nov 15;224:113666.
              doi: 10.1016/j.ejmech.2021.113666pubmed: 34245949google scholar: lookup
            3. Much ML, Leatherwood JL, Martinez RE, Silvers BL, Basta CF, Gray LF, Bradbery AN. Evaluation of an oral joint supplement on gait kinematics and biomarkers of cartilage metabolism and inflammation in mature riding horses. Transl Anim Sci 2020 Jul;4(3):txaa150.
              doi: 10.1093/tas/txaa150pubmed: 32968713google scholar: lookup
            4. Li Y, Chen L, Liu Y, Zhang Y, Liang Y, Mei Y. Anti-inflammatory effects in a mouse osteoarthritis model of a mixture of glucosamine and chitooligosaccharides produced by bi-enzyme single-step hydrolysis. Sci Rep 2018 Apr 4;8(1):5624.
              doi: 10.1038/s41598-018-24050-6pubmed: 29618773google scholar: lookup
            5. Song M, Hang TJ, Wang C, Yang L, Wen AD. Precolumn derivatization LC-MS/MS method for the determination and pharmacokinetic study of glucosamine in human plasma and urine. J Pharm Anal 2012 Feb;2(1):19-28.
              doi: 10.1016/j.jpha.2011.08.003pubmed: 29403716google scholar: lookup
            6. Esfandiari H, Pakravan M, Zakeri Z, Ziaie S, Pakravan P, Ownagh V. Effect of glucosamine on intraocular pressure: a randomized clinical trial. Eye (Lond) 2017 Mar;31(3):389-394.
              doi: 10.1038/eye.2016.221pubmed: 27768119google scholar: lookup
            7. Chang NJ, Lin YT, Lin CC, Wang HC, Hsu HC, Yeh ML. The repair of full-thickness articular cartilage defect using intra-articular administration of N-acetyl-D-glucosamine in the rabbit knee: randomized controlled trial. Biomed Eng Online 2015 Nov 18;14:105.
              doi: 10.1186/s12938-015-0100-ypubmed: 26582033google scholar: lookup
            8. Vitetta L, Coulson S, Linnane AW, Butt H. The gastrointestinal microbiome and musculoskeletal diseases: a beneficial role for probiotics and prebiotics. Pathogens 2013 Nov 14;2(4):606-26.
              doi: 10.3390/pathogens2040606pubmed: 25437335google scholar: lookup
            9. Motaghinasab S, Shirazi-Adl A, Parnianpour M, Urban JP. Disc size markedly influences concentration profiles of intravenously administered solutes in the intervertebral disc: a computational study on glucosamine as a model solute. Eur Spine J 2014 Apr;23(4):715-23.
              doi: 10.1007/s00586-013-3142-5pubmed: 24375329google scholar: lookup
            10. Henrotin Y, Chevalier X, Herrero-Beaumont G, McAlindon T, Mobasheri A, Pavelka K, Schön C, Weinans H, Biesalski H. Physiological effects of oral glucosamine on joint health: current status and consensus on future research priorities. BMC Res Notes 2013 Mar 26;6:115.
              doi: 10.1186/1756-0500-6-115pubmed: 23531101google scholar: lookup
            11. Osaki T, Azuma K, Kurozumi S, Takamori Y, Tsuka T, Imagawa T, Okamoto Y, Minami S. Metabolomic analyses of blood plasma after oral administration of D-glucosamine hydrochloride to dogs. Mar Drugs 2012 Aug;10(8):1873-1882.
              doi: 10.3390/md10081873pubmed: 23015778google scholar: lookup
            12. Reginster JY, Neuprez A, Lecart MP, Sarlet N, Bruyere O. Role of glucosamine in the treatment for osteoarthritis. Rheumatol Int 2012 Oct;32(10):2959-67.
              doi: 10.1007/s00296-012-2416-2pubmed: 22461188google scholar: lookup
            13. Jerosch J. Effects of Glucosamine and Chondroitin Sulfate on Cartilage Metabolism in OA: Outlook on Other Nutrient Partners Especially Omega-3 Fatty Acids. Int J Rheumatol 2011;2011:969012.
              doi: 10.1155/2011/969012pubmed: 21826146google scholar: lookup
            14. Azuma K, Osaki T, Tsuka T, Imagawa T, Okamoto Y, Takamori Y, Minami S. Effects of oral glucosamine hydrochloride administration on plasma free amino acid concentrations in dogs. Mar Drugs 2011;9(5):712-718.
              doi: 10.3390/md9050712pubmed: 21673884google scholar: lookup
            15. Simon RR, Marks V, Leeds AR, Anderson JW. A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals. Diabetes Metab Res Rev 2011 Jan;27(1):14-27.
              doi: 10.1002/dmrr.1150pubmed: 21218504google scholar: lookup
            16. Chen JK, Shen CR, Liu CL. N-acetylglucosamine: production and applications. Mar Drugs 2010 Sep 15;8(9):2493-516.
              doi: 10.3390/md8092493pubmed: 20948902google scholar: lookup
            17. Jackson CG, Plaas AH, Sandy JD, Hua C, Kim-Rolands S, Barnhill JG, Harris CL, Clegg DO. The human pharmacokinetics of oral ingestion of glucosamine and chondroitin sulfate taken separately or in combination. Osteoarthritis Cartilage 2010 Mar;18(3):297-302.
              doi: 10.1016/j.joca.2009.10.013pubmed: 19912983google scholar: lookup
            18. McCulloch DR, Wylie JD, Longpre JM, Leduc R, Apte SS. 10mM glucosamine prevents activation of proADAMTS5 (aggrecanase-2) in transfected cells by interference with post-translational modification of furin. Osteoarthritis Cartilage 2010 Mar;18(3):455-63.
              doi: 10.1016/j.joca.2009.10.014pubmed: 19909832google scholar: lookup
            19. de Grauw JC, van de Lest CH, van Weeren PR. Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experimental study. Arthritis Res Ther 2009;11(2):R35.
              doi: 10.1186/ar2640pubmed: 19272138google scholar: lookup
            20. Uitterlinden EJ, Koevoet JL, Verkoelen CF, Bierma-Zeinstra SM, Jahr H, Weinans H, Verhaar JA, van Osch GJ. Glucosamine increases hyaluronic acid production in human osteoarthritic synovium explants. BMC Musculoskelet Disord 2008 Sep 11;9:120.
              doi: 10.1186/1471-2474-9-120pubmed: 18786270google scholar: lookup
            21. Cassileth B, Trevisan C, Gubili J. Complementary therapies for cancer pain. Curr Pain Headache Rep 2007 Aug;11(4):265-9.
              doi: 10.1007/s11916-007-0202-8pubmed: 17686389google scholar: lookup
            22. Bruyere O, Reginster JY. Glucosamine and chondroitin sulfate as therapeutic agents for knee and hip osteoarthritis. Drugs Aging 2007;24(7):573-80.
              doi: 10.2165/00002512-200724070-00005pubmed: 17658908google scholar: lookup
            23. Gouze JN, Gouze E, Popp MP, Bush ML, Dacanay EA, Kay JD, Levings PP, Patel KR, Saran JP, Watson RS, Ghivizzani SC. Exogenous glucosamine globally protects chondrocytes from the arthritogenic effects of IL-1beta. Arthritis Res Ther 2006;8(6):R173.
              doi: 10.1186/ar2082pubmed: 17109745google scholar: lookup
            24. Towheed TE, Maxwell L, Anastassiades TP, Shea B, Houpt J, Robinson V, Hochberg MC, Wells G. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2005 Apr 18;2005(2):CD002946.
              doi: 10.1002/14651858.CD002946.pub2pubmed: 15846645google scholar: lookup
            25. Crosbie M, Vanderboom K, Souccar-Young J, Pearson W. Integrating Cartilage Explant Culture with Simulated Digestion and Hepatic Biotransformation Refines In Vitro Screening of Joint Care Nutraceuticals. Methods Protoc 2025 Aug 6;8(4).
              doi: 10.3390/mps8040091pubmed: 40863741google scholar: lookup
            26. Kearney CM, Korthagen NM, Plomp SGM, Labberté MC, de Grauw JC, van Weeren PR, Brama PAJ. A Translational Model for Repeated Episodes of Joint Inflammation: Welfare, Clinical and Synovial Fluid Biomarker Assessment. Animals (Basel) 2023 Oct 12;13(20).
              doi: 10.3390/ani13203190pubmed: 37893914google scholar: lookup
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