betadex and Arthritis--Rheumatoid

The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in rheumatic diseases depends on their concentrations within the joint. We determined piroxicam concentrations in plasma and synovial fluid (SF) after a single oral dose of 20 mg in the form of one tablet of piroxicam-beta-cyclodextrin.. 45 patients, aged 21 to 84 years, presenting with an effusion of the knee, related to degenerative or inflammatory joint disease, were included in this study after having given their written consent. One blood and one SF sample were drawn concomitantly in each patient from 0.5 to 48 h after NSAID administration. Piroxicam assays were performed by high performance liquid chromatography. Pharmacokinetic parameters were obtained from the mean plasma and synovial concentrations measured at various sampling times.. The peak concentration was higher in plasma (2.51+/-0.25 microg/ml) than in SF (1.31+/-0.76 microg/ml), but the elimination half-life was much longer in SF (90.7 h) than in plasma (32.5 h). The SF/plasma area under the concentration-time curve ratio (evaluating the quantity of NSAID transferred from the blood to the joint) was equal to 0.39.. Piroxicam contained in piroxicam-beta-cyclodextrin diffused well into the SF where its pharmacokinetic profile corresponded to that of a long half-life NSAID.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Arthritis, Rheumatoid; beta-Cyclodextrins; Cyclodextrins; Drug Combinations; Female; Half-Life; Humans; Joint Diseases; Knee Joint; Male; Middle Aged; Piroxicam; Synovial Fluid

The clinical relevance of piroxicam-beta-cyclodextrin (PBC) in the long-term treatment of osteoarthritis and rheumatoid arthritis is reviewed. Two hundred and twenty-five patients--one hundred with rheumatoid arthritis and one hundred and twenty five with osteoarthritis--were enrolled in a double-blind, randomised, controlled study versus piroxicam. Drugs were administered once-daily, for twelve weeks. The indices of efficacy (pain intensity, severity of inflammation, functional impairment evaluated at 0,2,4,8 and 12 weeks showed the good analgesic effect of piroxicam without significant differences between its two formulations. Tolerance appeared to be better in the group of patients treated with PBC than in the one treated with piroxicam. Both the incidence and severity of side effects were lower for patients treated with PBC. The majority of side effects were related to the gastrointestinal tract. The study suggests that PBC, used in the long term treatment of rheumatic diseases, improves the safety of piroxicam without affecting its efficacy. In another study, thirty patients with chronic osteoarthritis were randomly assigned to receive PBC or tenoxicam daily for eight weeks. Both drugs effectively reduced pain, inflammation, and functional limitation of the affected joints. Endoscopy revealed minor post-treatment mucosal lesions; these tended to be less severe with PBC than with tenoxicam. The clinical experience in the long-term treatment of rheumatic conditions indicates that the microencapsulation of piroxicam as piroxicam-beta-cyclodextrin has provided a new drug with a superior tolerability compared to the parent compound without affecting its high efficacy on the symptoms of the primary disease.

Topics: Adult; Aged; Aged, 80 and over; Antirheumatic Agents; Arthritis, Rheumatoid; beta-Cyclodextrins; Cyclodextrins; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Osteoarthritis; Pain; Piroxicam

Tranilast (TL), an antiallergic agent, has been clinically used in the treatment of bronchial asthma, although its clinical use has been limited by its poor solubility in water, photodegradation and systemic side effects. In this study, we prepared a gel ointment containing TL nanoparticles (TLnano gel ointment), and investigated its usefulness. In addition, we demonstrated the preventive effects of the TLnano gel ointment on inflammation in adjuvant-induced arthritis (AA) rats. The TLnano gel ointment was prepared using Bead Smash 12 (a bead mill) and additives including sodium docusate, 2-hydroxypropyl-β-cyclodextrin, methylcellulose and Carbopol 934; the mean particle diameter of the TL nanoparticles was 71.0±25.4 nm. In in vitro skin penetration experiments, the amount of penetrated TL, the penetration rate (Jc) and the penetration coefficient through the skin (Kp) of the TLnano gel ointment were significantly higher than those of a gel ointment containing TL microparticles (TLmicro gel ointment; particle diameter 50.5±26.3 µm). The TL concentrations in the skin tissue and plasma of rats receiving the TLnano gel ointment were also higher than in rats receiving the TLmicro gel ointment. In addition, the application of the TLnano gel ointment attenuated the increase in paw edema of the hind feet of AA rats in comparison with AA rats treated with the TLmicro gel ointment. These results suggest that TL nanoparticles can be applied to the formulation of a transdermal system, and that a transdermal formulation using TL nanoparticles might be a delivery option for the clinical treatment of RA.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acrylates; Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Arthritis, Rheumatoid; beta-Cyclodextrins; Edema; Gels; Inflammation; Male; Methylcellulose; Nanoparticles; Ointments; ortho-Aminobenzoates; Particle Size; Rats; Rats, Wistar; Skin; Skin Absorption; Solubility