lornoxicam and Osteoarthritis

Lornoxicam (chlortenoxicam), a new nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class with analgesic, anti-inflammatory and antipyretic properties, is available in oral and parenteral formulations. It is distinguished from established oxicams by a relatively short elimination half-life (3 to 5 hours), which may be advantageous from a tolerability standpoint. Data from preliminary clinical trials suggest that lornoxicam is as effective as the opioid analgesics morphine, pethidine (meperidine) and tramadol in relieving postoperative pain following gynaecological or orthopaedic surgery, and as effective as other NSAIDs after oral surgery. Lornoxicam was also as effective as other NSAIDs in relieving symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute sciatica and low back pain. Lornoxicam has a tolerability profile characteristic of an NSAID, with gastrointestinal disturbances being the most common adverse events. Limited clinical experience to date suggests that, as with a number of other NSAIDs, lornoxicam may provide a better-tolerated alternative or adjuvant to opioid analgesics for the management of moderate to severe pain. It has also demonstrated potential as an alternative to other NSAIDs for the management of arthritis and other painful and inflammatory conditions. These preliminary findings require confirmation in further comparative and long term studies.

Topics: Absorption; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Dosage Forms; Drug Interactions; Humans; Low Back Pain; Migraine Disorders; Osteoarthritis; Pain; Pain, Postoperative; Piroxicam; Spondylitis, Ankylosing; Tissue Distribution

To compare the efficacy and tolerability of lornoxicam and diclofenac in the treatment of patients with osteoarthritis (OA) over 12 weeks and to assess the efficacy and tolerability of lornoxicam over a followup period of 40 weeks.. In a double blind, parallel group study, 135 patients (mean age 63 years) with OA of the hip and/or knee were randomized to receive lornoxicam 4 mg 3 times daily (tid), lornoxicam 8 mg twice daily (bid), or diclofenac 50 mg tid for 12 weeks. 85 patients who completed this 12 week treatment period subsequently received lornoxicam 4 mg tid or 8 mg bid for up to 40 weeks.. Over the initial 12 week treatment period, intention-to-treat analysis revealed improvements in the functional index of severity for OA in all 3 groups by -1.5 to -1.9 points and pairwise testing demonstrated significant intergroup equivalence (p < 0.033). Confirmatory analysis demonstrated the expected efficacy as outlined in the sample size calculation. The percentage of patients showing improvements in disease activity (about 46%) and pain intensity (42 to 48%) was also similar and a clear majority of patients also reported "some" or "excellent" pain relief (80 to 89%). A per protocol analysis produced similar results. During the 40 week lornoxicam followup treatment period there was slight deterioration in the functional index of severity of OA (0.3 to 1.1 points). This minor change may reflect the natural course of the disease rather than a loss of efficacy in lornoxicam. Disease activity and pain intensity continued to improve but in a lesser proportion of patients (< 23%) compared to the previous phase. Nevertheless, a similar high percentage of patients (78 to 89%) reported "some" or "excellent" pain relief. Adverse events in both phases of this study were consistent with those commonly reported during treatment with nonsteroidal antiinflammatory drugs and included headache and gastrointestinal events. There was no difference in the frequency or severity of adverse events between any of the treatment groups. Lornoxicam was well tolerated in the long term.. Lornoxicam 4 mg tid and 8 mg bid were as effective as diclofenac 50 mg tid for the treatment of OA. There was no significant difference in tolerability of these regimens. Thus, lornoxicam appears to be a useful therapeutic alternative to diclofenac in patients with OA.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Osteoarthritis; Piroxicam; Treatment Outcome

Lornoxicam is a new non-steroidal anti-inflammatory agent (NSAID) with a similar pharmacological profile to other oxicams and a potency 10 times greater than piroxicam. A multicentre, randomised, double blind, parallel group study was undertaken to compare the efficacy and tolerance of four weeks' treatment with lornoxicam (6 mg once daily, 4 mg twice daily, and 6 mg twice daily) and placebo in patients with osteoarthritis of the hip or knee. A dose related efficacy of lornoxicam was shown by the numbers of patients in each treatment group who withdrew from the trial owing to inadequate symptom relief (12/40 (30%) receiving placebo, 6/40 (15) receiving lornoxicam 6 mg daily, 4/40 (10%) receiving lornoxicam 8 mg daily, and none receiving lornoxicam 12 mg daily). This effect was confirmed by pain relief scores, which were significantly better than placebo during treatment with lornoxicam 8 mg and 12 mg daily, the effect of 12 mg daily being significantly superior to that of 8 mg daily. Similar results were obtained from functional status scores. Mean functional index (Lequesne) scores were significantly greater than placebo only at a daily dose of 12 mg lornoxicam. Lornoxicam was generally well tolerated, though some gastrointestinal side effects were seen as has been reported with other NSAIDs. Laboratory investigations showed no evidence of drug toxicity.

Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Drug Administration Schedule; Dyspepsia; Female; Hip Joint; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Pain; Piroxicam

Three studies reported here have confirmed that lornoxicam is effective in osteoarthritis and the ideal dose appears to be 12 mg daily. Overall, lornoxicam appears to be a useful drug in the treatment of both osteo- and rheumatoid arthritis, from the data presently available.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Female; Humans; Male; Middle Aged; Osteoarthritis; Piroxicam

Osteoarthritis is a chronic joint disease characterized by chronic inflammation, progressive destruction of articular cartilage, and subchondral bone sclerosis. When compared to individual treatment, the combined administration of genes and small-molecule drugs for osteoarthritis may not only provide superior inflammation control and pain relief, but may also repair cartilage damage. Here, cationic liposomes (CL) were used to deliver small hydrophobic drugs and microRNA into chondrocytes to treat osteoarthritis. Lornoxicam cationic liposomes (Lnxc-CL) were prepared by film dispersion, and loaded with microRNA-140 (miR-140) by electrostatic interaction to obtain cationic liposomes co-loaded with lornoxicam and miR-140 (Lnxc-CL/miR-140). The prepared Lnxc-CL/miR-140 had a particle size of 286.6 ± 7.3 nm, polydispersity index (PDI) of 0.261 ± 0.029 and zeta potential of 26.5 ± 0.5 mV and protected miR-140 from RNase degradation for 24 h. Lnxc-CL/miR-140 was evaluated for its ability to regulate gene expression in chondrocytes in vitro and to provide in vivo therapeutic effects for knee osteoarthritis in rats. The results of in vitro uptake experiments and polymerase chain reaction (PCR) analysis showed that Lnxc-CL/miR-140 efficiently delivered miR-140 into chondrocytes and up-regulated the expression of miR-140 and COL2A1 mRNA. Pharmacodynamics studies demonstrated that Lnxc-CL/miR-140 effectively treated osteoarthritis by eliminating joint inflammation and repairing damaged cartilage cells, with superior therapeutic effects compared to Lnxc or miR-140 alone. Overall, the findings of this study support the co-delivery of Lnxc and miR-140 with cationic liposomes as a potential new therapeutic strategy for the treatment of osteoarthritis.

Topics: Animals; Injections, Intra-Articular; Liposomes; MicroRNAs; Osteoarthritis; Piroxicam; Rats