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DOI: 10.1055/s-0031-1296294
Influence on analgesic activity and serum levels after meloxicam complexation with beta-cyclodextrin in mice and rats
Publication History
Publication Date:
02 December 2011 (online)

Abstract
The aim of the present study was to evaluate and compare the analgesic activity and serum levels of meloxicam (CAS 71125-38-7) after administration of meloxicam associated with beta-cyclodextrin (BCD, CAS 7585-39-9) and unmodified meloxicam. The analgesic activity was measured using the plantar test (rats) and the writhing test (mice). In the plantar test, BCD-meloxicam (3 mg/kg and 10 mg/kg orally) showed higher analgesic activity than corresponding doses of meloxicam alone; in the writhing test BCD-meloxicam (7 mg/kg and 15 mg/kg orally) showed stronger analgesic activity than unmodified meloxicam. Serum levels of meloxicam were significantly higher, at 0.5 h and 1 h after administration of BCD-meloxicam orally than those of unmodified meloxicam (both dosed at 10 mg/kg). The present results suggest that association with beta-cyclodextrin increases the analgesic activity of meloxicam. This may be due to an icreased systemic bioavailability of meloxicam after oral administration of its complex with beta-cyclodextrin.
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References
- 1 Engelhardt G, Bogel R, Schnitzler C, Utzmann R. Meloxicam: influence on arachidonic acid metabolism. Part II. In vivo findings. Biochem Pharmacol. 1996; 51: 29-38
- 2 Engelhardt G, Bogel R, Schnitzer C, Utzmann R. Meloxicam: influence on arachidonic acid metabolism. Part I. In vitro findings. Biochem Pharmacol. 1996; 51: 21-28
- 3 Engelhardt G, Homma D, Schlegel K, Schnitzler C, Utzmann R. General pharmacology of meloxicam. Part II: Effects on blood pressure, blood flow, heart rate, ECG, respiratory minute volume and interactions with paracetamol, pirenzepine, chlorthalidone, phenprocoumon and tolbutamide. Gen Pharmacol. 1996; 27: 679-88
- 4 Engelhardt G, Homma D, Schlegel K, Schnitzler C, Utzmann R. General pharmacology of meloxicam. Part I: Effects on CNS, gastric emptying, intestinal transport, water, electrolyte and creatinine excretion. Gen Pharmacol. 1996; 27: 673-7
- 5 Strickley RG. Solubilizing excipients in oral and injectable formulations. Pharm Res. 2004; 21: 201-30
- 6 Banerjee R, Chakraborty H, Sarkar M. Host-guest complexation of oxicam NSAIDs with beta-cyclodextrin. Biopolymers. 2004; 75: 355-65
- 7 Naidu NB, Chowdary KP, Murthy KV, Satyanarayana V, Hayman AR, Becket G. Physicochemical characterization and dissolution properties of meloxicam-cyclodextrin binary systems. J Pharm Biomed Anal. 2004; 35: 75-86
- 8 VijayaKumar SG, Mishra DN. Analgesic, antiinflammatory, and ulcerogenic studies of meloxicam solid dispersion prepared with polyethylene glycol 6000. Methods Find Exp Clin Pharmacol. 2006; 28: 419-22
- 9 Amado CA, Taniguchi SF, Sudo LS, Kimura E, Oga S. Effect of piroxicam beta-cyclodextrin complex on experimental inflammation. Gen Pharmacol. 1995; 26: 809-13
- 10 Warrington S. Effects of piroxicam-beta-cyclodextrin on the gastrointestinal tract. Eur J Rheumatol Inflamm. 1993; 12: 29-37
- 11 Deroubaix X, Stockis A, Allemon AM, Lebacq E, Acerbi D, Ventura P. Oral bioavailability of CHF1194, an inclusion complex of piroxicam and beta-cyclodextrin, in healthy subjects under single dose and steady-state conditions. Eur J Clin Pharmacol. 1995; 47: 531-6
- 12 Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain. 1983; 16: 109-10
- 13 Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1988; 32: 77-88
- 14 Collier HO, Dinneen LC, Johnson CA, Schneider C. The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br J Pharmacol Chemother. 1968; 32: 295-310
- 15 Ghorab MM, Abdel-Salam HM, ElSayad MA, Mekhel MM. Tablet formulation containing meloxicam and beta-cyclodextrin: mechanical characterization and bioavailability evaluation. AAPS Pharm Sci Tech. 2004; 5: e59
- 16 Nalluri BN, Chowdary KP, Murthy KV, Becket G, Crooks PA. Tablet formulation studies on nimesulide and meloxicam-cyclodextrin binary systems. AAPS Pharm Sci Tech. 2007; 8 article 36.
- 17 Reginster JY, Franchimont P. Piroxicam-beta-cyclodextrin in the treatment of acute pain of rheumatic disease. Eur J Rheumatol Inflamm. 1993; 12: 38-46
- 18 Dequeker J, Hawkey C, Kahan A, Steinbruck K, Alegre C, Baumelou E et al Improvement in gastrointestinal tolerability of the selective cyclooxygenase (COX)-2 inhibitor, meloxicam, compared with piroxicam: results of the Safety and Efficacy Large-scale Evaluation of COX-inhibiting Therapies (SELECT) trial in osteoarthritis. Br J Rheumatol. 1998; 37: 946-51