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Four-week toxicity and toxicokinetics of piroxicam and hyaluronic acid combination following intra-articular injection in normal rats

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Abstract

The 4-week toxicity and toxicokinetics of a piroxicam (PX)/ hyaluronic acid (HA) combination were assessed in normal rats after intra-articular (IA) injection into the knee. Rats received PX or HA alone or in combination intra-articularly once a week for 4 weeks at an each dose of 4 mg/kg, a maximum feasible dose. There were transient and reversible changes in food consumption, hematology and serum chemistry, and minimal hypertrophy and hyperplasia of synovial cells on histopathological observation. However, no increase in toxicity was observed with the combination of PX and HA with no dose-dependent manner. Systemic exposure of HA and PX was similar throughout the experimental period when administered alone or concurrently, indicating that there were no pharmacokinetic drug-drug interactions, affecting exposure of either therapeutic agent. This study will support future studies of the IA combination of PX and HA in osteoarthritis-induced animal models and even patients.

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References

  1. Moreland, L. W. Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action. Arthritis Res Ther 5:54–67 (2003).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Balazs, E. A., Watson, D., Huff, I. F., & Roseman, S. Hyaluronic acid in synovial fluid. I. Molecular parameters of hyaluronic acid in normal and arthritis human fluids. Arthritis Rheum 10:357–376 (1967).

    Article  PubMed  CAS  Google Scholar 

  3. Dahl, L. B., Dahl, I. M., Engstrom-Laurent, A., & Granath, K. Concentration and molecular weight of sodium hyaluronate in synovial fluid from patients with rheumatoid arthritis and other arthropathies. Ann Rheum Dis 44:817–822 (1985).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Lo, G. H., LaValley, M., McAlindon, T., & Felson, D. T. Intra-articular hyaluronic acid in treatment of knee osteoarthritis: a meta-analysis. JAMA 290:3115–3121 (2003).

    Article  PubMed  CAS  Google Scholar 

  5. Sun, S. F. et al. Efficacy of intra-articular hyaluronic acid in patients with osteoarthritis of the ankle: a prospective study. Osteoarthr Cartil 14:867–874 (2006).

    Article  PubMed  Google Scholar 

  6. Dixon, A. S., Jacoby, R. K., Berry, H., & Hamilton, E. B. Clinical trial of intra-articular injection of sodium hyaluronate in patients with osteoarthritis of the knee. Curr Med Res Opin 11:205–213 (1988).

    Article  PubMed  CAS  Google Scholar 

  7. Desai, A., Ramankutty, S., Board, T., & Raut, V. Does intraarticular steroid infiltration increase the rate of infection in subsequent total knee replacements? Knee 16:262–264 (2009).

    Article  PubMed  Google Scholar 

  8. Jones, A. C., Pattrick, M., Doherty, S., & Doherty, M. Intra-articular hyaluronic acid compared to intra-articular triamcinolone hexacetonide in inflammatory knee osteoarthritis. Osteoarthr Cartil 3:269–273 (1995).

    Article  PubMed  CAS  Google Scholar 

  9. Lee, S. C., Rha, D. W., & Chang, W. H. Rapid analgesic onset of intra-articular hyaluronic acid with ketorolac in osteoarthritis of the knee. J Back Musculoskelet Rehabil 24:31–38 (2011).

    PubMed  Google Scholar 

  10. Mihara, M., Higo, S., Uchiyama, Y., Tanabe, K., & Saito, K. Different effects of high molecular weight sodium hyaluronate and NSAID on the progression of the cartilage degeneration in rabbit OA model. Osteoarthr Cartil 15:543–549 (2007).

    Article  PubMed  CAS  Google Scholar 

  11. Oztuna, V., Eskandari, M., Bugdayci, R., & Kuyurtar, F. Intra-articular injection of tenoxicam in osteoarthritic knee joints with effusion. Orthopedics 30:1039–1042 (2007).

    PubMed  Google Scholar 

  12. Unlu, Z., Ay, K., & Tuzun, C. Comparison of intra-articular tenoxicam and oral tenoxicam for pain and physical functioning in osteoarthritis of the knee. Clin Rheumatol 25:54–61 (2006).

    Article  PubMed  Google Scholar 

  13. Colbert, S. T., Curran, E., O’Hanlon, D. M., Moran, R., & McCarroll, M. Intra-articular tenoxicam improves postoperative analgesia in knee arthroscopy. Can J Anaesth 46:653–657 (1999).

    Article  PubMed  CAS  Google Scholar 

  14. Elhakim, M., Fathy, A., Elkott, M., & Said, M. M. Intraarticular tenoxicam relieves post-arthroscopy pain. Acta Anaesthesiol Scand 40:1223–1226 (1996).

    Article  PubMed  CAS  Google Scholar 

  15. Saricaoglu, F. et al. Effect of intraarticular injection of lornoxicam on the articular cartilage & synovium in rat. Indian J Med Res 127:362–365 (2008).

    PubMed  CAS  Google Scholar 

  16. Irwin, M. G., Cheung, K. M., Nicholls, J. M., & Thompson, N. Intra-articular injection of ketorolac in the rat knee joint: effect on articular cartilage and synovium. Br J Anaesth 80:837–839 (1998).

    Article  PubMed  CAS  Google Scholar 

  17. Ozyuvaci, H. et al. Intra-articular injection of tenoxicam in rats: assessment of the local effects on the articular cartilage and synovium. J Int Med Res 32:312–316 (2004).

    Article  PubMed  CAS  Google Scholar 

  18. Hobbs, D. C., & Twomey, T. M. Metabolism of piroxicam by laboratory animals. Drug Metab Dispos 9:114–118 (1981).

    PubMed  CAS  Google Scholar 

  19. Perini, J. A., Vianna-Jorge, R., Brogliato, A. R., & Suarez- Kurtz, G. Influence of CYP2C9 genotypes on the pharmacokinetics and pharmacodynamics of piroxicam. Clin Pharmacol Ther 78:362–369 (2005).

    Article  PubMed  CAS  Google Scholar 

  20. Leach, J. B., & Schmidt, C. E. Hyaluronan. Encyclopedia of Biomaterials and Biomedical Engineering Marcel Dekker 779–789 (2004).

    Google Scholar 

  21. Lindqvist, U. et al. Elimination of stabilised hyaluronan from the knee joint in healthy men. Clin Pharmacokinet 41:603–613 (2002).

    Article  PubMed  CAS  Google Scholar 

  22. Necas, J., Bartosikova, L., Brauner, P., & Kolar, J. Hyaluronic acid (hyaluronan): a review. Veterinarni Medicina 53:397–411 (2008).

    CAS  Google Scholar 

  23. Roskos, L. K., & Boudinot, F. D. Effects of dose and sex on the pharmacokinetics of piroxicam in the rat. Biopharm Drug Dispos 11:215–225 (1990).

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Dong-A Pharmaceutical Co. Ltd., Giheung-gu, Yongin, Gyeonggi, 446-905, Korea

    Chan Woong Park, Kyung Wan Ma, Sun Woo Jang & Miwon Son

  2. College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnamgu, Cheonan, Chungnam, 330-714, Korea

    Myung Joo Kang

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  1. Chan Woong Park
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Correspondence to Myung Joo Kang.

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Park, C.W., Ma, K.W., Jang, S.W. et al. Four-week toxicity and toxicokinetics of piroxicam and hyaluronic acid combination following intra-articular injection in normal rats. Mol. Cell. Toxicol. 10, 319–328 (2014). https://doi.org/10.1007/s13273-014-0036-5

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  • DOI: https://doi.org/10.1007/s13273-014-0036-5

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