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At least 19 recordsLinked to original sources
PubMed1998

Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients. International MELISSA Study Group. Meloxicam Large-scale International Study Safety Assessment.

Although widely used, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with a high incidence of gastrointestinal (GI) side-effects. Inhibition of the cyclooxygenase (COX) enzyme is the basis for both the efficacy and toxicity of NSAIDs. The discovery of two COX isoforms, constitutive COX-1 and inducible COX-2, has led to the hypothesis that selective inhibition of COX-2 will minimize the potential for GI toxicity without compromising efficacy. The Meloxicam Large-scale International Study Safety Assessment (MELISSA) trial reported here was therefore set up to investigate the tolerability of meloxicam, a preferential inhibitor of COX-2, compared to diclofenac. MELISSA was a large-scale, double-blind, randomized, international, prospective trial, conducted over 28 days in patients with symptomatic osteoarthritis. Patients received either meloxicam 7.5 mg or diclofenac 100 mg slow release, the recommended doses for the treatment of osteoarthritis. Evaluation of the profile of adverse events was the main aim of the trial, together with assessment of efficacy. A total of 9323 patients received treatment (4635 and 4688 in the meloxicam and diclofenac groups, respectively). Significantly fewer adverse events were reported by patients receiving meloxicam. This was attributable to fewer GI adverse events (13%) compared to diclofenac (19%; P < 0.001). Of the most common GI adverse events, there was significantly less dyspepsia (P < 0.001), nausea and vomiting (P < 0.05), abdominal pain (P < 0.001) and diarrhoea (P < 0.001) with meloxicam compared to diclofenac. Five patients on meloxicam experienced a perforation, ulcer or bleed vs seven on diclofenac (not significant). No endoscopically verified ulcer complication was detected in the meloxicam group compared to four with diclofenac. There were five patient days of hospitalization in patients on meloxicam compared to 121 with diclofenac. Adverse events caused withdrawal from the study in 254 patients receiving meloxicam (5.48%) compared to 373 (7.96%) on diclofenac (P < 0.001). These differences were attributable to differences in reported GI adverse events (3.02% on meloxicam vs 6.14% on diclofenac; P < 0.001). Differences in efficacy, as assessed by visual analogue scales, consistently favoured diclofenac. In all instances, 95% confidence intervals did not cross zero, suggesting a statistically significant effect. However, differences were small (4.5-9.01% difference) and did not reach pre-determined levels of clinical significance. Nevertheless, significantly more patients discontinued meloxicam because of lack of efficacy (80 out of 4635 vs 49 out of 4688; P < 0.01). The MELISSA trial confirms earlier studies suggesting that meloxicam has a significantly improved GI tolerability profile in comparison with other NSAIDs, including diclofenac. These results may in part reflect the preferential COX-2 selectivity of meloxicam, although the dose and other aspects of tolerability may be important. These results may provide support for the hypothesis that selective inhibition of COX-2 relative to COX-1 might be an effective approach towards improved NSAID therapy.

Aged↗
PubMed1996

A 4-week, double-blind, parallel-group study to compare the gastrointestinal effects of meloxicam 7.5 mg, meloxicam 15 mg, piroxicam 20 mg and placebo by means of faecal blood loss, endoscopy and symptom evaluation in healthy volunteers.

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which preferentially inhibits cyclooxygenase-2 (COX-2) over cyclooxygenase-1 (COX-1). Gastrointestinal (GI) tolerability of meloxicam 7.5 and 15 mg vs piroxicam 20 mg was evaluated in a 4-week, double-blind, parallel group, placebo-controlled study in 51 healthy male volunteers, using a combination of oesphago-gastro-duodenal endoscopy, faecal blood loss measurement and symptom evaluation. Analysis of covariance found no significant difference in faecal blood loss between the groups. However, significantly higher bleeding was found with piroxicam 20 mg compared with placebo using a Student's t-test on the weighted means. Endoscopy score were significantly higher with piroxicam than with meloxicam 7.5 mg or placebo (P < 0.01). A significant difference from baseline was observed in the meloxicam 15 mg and piroxicam groups (P < 0.05), but not in the meloxicam 7.5 mg and placebo groups. Six piroxicam-treated volunteers were withdrawn following a poor endoscopic score, but no such withdrawals occurred in the meloxicam and placebo groups (P < 0.01). Meloxicam 7.5 mg caused less GI damage compared with piroxicam 20 when administered to healthy young volunteers for 28 days; a possible dose dependency effect in GI tolerability was also suggested for meloxicam 7.5 and 15 mg, in relation to endoscopic findings.

Adult↗
PubMed1996

The efficacy and tolerability of an 8-day administration of intravenous and oral meloxicam: a comparison with intramuscular and oral diclofenac in patients with acute lumbago. German Meloxicam Ampoule Study Group.

In this controlled, randomized, parallel and open multicentre study, the efficacy and tolerability of a regimen comprising intravenous (i.v.) meloxicam followed by oral therapy was compared with a standard regimen of intramuscular (i.m.) diclofenac followed by oral dosing in patients with acute lumbago. Of a total of 183 patients, 92 were randomized to receive meloxicam 15 mg i.v. on day 1 followed by 7 days oral treatment with one 15 mg tablet daily, and 91 patients received diclofenac 75 mg i.m. on day 1 followed by 7 days treatment with one 100 mg slow release tablet daily. Pain on movement and limitation of activities were assessed by patients and physicians using questionnaires. Meloxicam i.v. demonstrated a significantly faster median time of onset of analgesic action (30 minutes), compared with diclofenac i.m. (60 minutes). The reduction in pain during movement 30 minutes after injection was also significantly in favour of meloxicam. Assessments of global efficacy indicated that meloxicam was significantly better than diclofenac as rated by investigators (p = 0.02) and patients (p = 0.01). Moreover, the rating of investigators and patients for local and global tolerance was significantly in favour of meloxicam (p < 0.05) and improvements in the quality of life were almost significant (p = 0.053). Fewer adverse events, particularly of a gastrointestinal (GI) nature, occurred in the meloxicam group compared with the diclofenac group. This study therefore demonstrates that meloxicam 15 mg i.v. followed by oral therapy is both efficacious and well tolerated in the treatment of acute lumbago, and compares favourably with the standard NSAID, diclofenac, in this indication.

Administration, Oral↗
PubMed1996

A double-blind, three-week study to compare the efficacy and safety of meloxicam 7.5 mg and meloxicam 15 mg in patients with rheumatoid arthritis.

A multicentre, double-blind, randomized study was conducted in patients with rheumatoid arthritis (RA) in order to compare the efficacy and safety of two different doses of meloxicam, a new preferential cyclooxygenase-2 (COX-2) inhibitor. Four hundred and twenty-three patients were randomized to receive once-daily oral meloxicam 7.5 mg (n = 216) or meloxicam 15 mg (n = 207) for 3 weeks. The Ritchie joint index and pain in the morning were significantly improved versus baseline (P < 0.001) in both groups. There were no significant differences between the effects of each dose with respect to these measures nor with respect to final assessment of global efficacy by the patients. However, the 15 mg dose was associated with a significantly (P < 0.05) better effect on morning stiffness and grip strength. No differences between the doses were observed with regard to the other secondary efficacy parameter (pain at night, body weight and erythrocyte sedimentation rate). Both doses of meloxicam were well tolerated. There were no differences between the doses with respect to global tolerance as assessed by the patient and the patients, 'general condition'. In conclusion, meloxicam at a once-daily dose of either 7.5 or 15 mg is well tolerated and effective in the treatment of patients with RA.

Adult↗
PubMedDate not supplied

Comparison of the onset and intensity of action of intramuscular meloxicam and oral meloxicam in patients with acute sciatica.

In this randomized, double-blind, double-dummy trial, 113 patients with acute sciatica were treated with a single 15-mg dose of meloxicam given intramuscularly (n = 54) or orally (n = 59). There was a significant improvement in induced pain (as measured by using the straight-leg-raising test) in both treatment groups at 60 minutes (P < 0.005), and there was a significant difference in favor of the intramuscular formulation in terms of the time to maximum improvement of induced pain (P = 0.01). Changes in spontaneous pain were similar in both treatment groups and were significant versus baseline (P < 0.01) at 30 minutes after study drug administration. Global efficacy evaluations by both the patients and investigators confirmed that meloxicam 15 mg in an intramuscular or oral formulation was effective in relieving pain in patients with acute sciatica. Meloxicam was generally well tolerated, and the local tolerability of the intramuscular injection was found to be excellent on the basis of both clinical evaluation and assessment of creatine phosphokinase levels.

Acute Disease↗
PubMed1995

Anti-inflammatory, analgesic, antipyretic and related properties of meloxicam, a new non-steroidal anti-inflammatory agent with favourable gastrointestinal tolerance.

The anti-inflammatory, analgesic and antipyretic properties of the new non-steroidal anti-inflammatory agent, meloxicam, were investigated in a variety of animal models and compared with the properties of piroxicam, diclofenac, indomethacin and several other NSAIDs. With respect to the total effect of a single oral dose, the anti-exudative effect of meloxicam on carrageenan-induced oedema in the rat exceeded that of all the NSAIDs included in the comparison. Additionally, meloxicam showed the greatest potency of all the compounds examined with respect to adjuvant-induced arthritis in the rat, the granuloma pouch model and the cotton pellet test in the rat. Unlike indomethacin, in the carrageenan pleurisy model in the rat, meloxicam caused both a dose-dependent reduction in exudate volume and also inhibition of leucocyte migration. Meloxicam showed a strong and lasting effect on inflammatory pain in the rat. Like other NSAIDs, but unlike dipyrone, meloxicam had no effect in the hot plate and tail clamp tests, which are used to identify weak central analgesic effects. Unlike dipyrone and like indomethacin, meloxicam had no effect in a model of visceral distention pain. In common with other NSAIDs, meloxicam had no influence on the body temperature of normothermic rats in the anti-inflammatory dose range, but did reduce yeast-induced fever in the rat in a dose-dependent manner. Like piroxicam, meloxicam had a uricosuric effect on rats treated with oxonic acid. Low-dose meloxicam inhibited both bradykinin-induced and PAF-induced bronchospasm in the guinea-pig, but had no effect on acetylcholine-induced bronchospasm. Piroxicam had greater ulcerogenic effects in the rat stomach than meloxicam. The therapeutic range of meloxicam in the rat, with regard to inhibition of adjuvant arthritis, was several times greater than that of piroxicam, indomethacin, diclofenac and naproxen.

Animals↗
PubMed1999

Comparison of inhibitory effects of meloxicam and diclofenac on human thromboxane biosynthesis after single doses and at steady state.

OBJECTIVE: To evaluate the extent of human cyclooxygenase-1 (COX-1) inhibition by meloxicam, which has been reported to preferentially inhibit cyclooxygenase-2 (COX-2). The effects of meloxicam were compared with those of diclofenac, a nonselective COX inhibitor. METHODS: COX-1 inhibition was determined by measuring thromboxane B2 (TXB2)-generation from clotting whole blood ex vivo after single oral doses of 7.5 and 15 mg meloxicam and 75 mg diclofenac and at steady state (15 mg meloxicam daily and 150 mg diclofenac daily). The effect was expressed as percentage inhibition of serum TXB2 generation and was directly related to the serum drug concentration with use of a standard sigmoidal E(max) model. RESULTS: In terms of inhibition of TXB2 generation, diclofenac was about 1 order of magnitude more potent than meloxicam, indicated by a diclofenac EC50 (concentration of drug required to cause 50% of maximum effect) that was about 10 times lower than that of meloxicam (EC50 diclofenac single doses: 37.50+/-29.64; EC50 meloxicam single doses: 677.50+/-189.08). However, serum concentrations of meloxicam after administration of 15 mg were approximately 10-fold higher than those of diclofenac. Therefore there was no statistically significant difference in the area under the effect time curve (P = .115) and the mean effect (P = .424) between meloxicam and diclofenac. The EC50 of both drugs was significantly higher at steady state (diclofenac steady state: 87.07+/-55.24 ng/mL; meloxicam steady state: 1850.12+/-829.93 ng/mL) than after a single dose (P < .001). CONCLUSION: These data show that meloxicam inhibits TXB2 generation at clinically relevant doses, although less potently than diclofenac. Thus our data suggest that the COX-2 preference of meloxicam observed in vitro may not result in clinical advantages when the higher dose of 15 mg is needed. Because of the increase in EC50 at steady state, COX-1 is relatively spared when the lower dose of 7.5 mg is administered.

Administration, Oral↗
PubMed1997

Efficacy and safety of meloxicam in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the efficacy and safety of meloxicam, a new acidic enolic nonsteroidal anti-inflammatory drug, at doses of 7.5 and 15 mg once daily in patients with rheumatoid arthritis (RA). METHODS: Meloxicam 15 and 7.5 mg daily was administered for 21 days in this double blind, randomized, placebo controlled study. 159 patients received meloxicam 7.5 mg, 162 received meloxicam 15 mg, and 147 received placebo. RESULTS: Meloxicam 15 mg once daily was significantly superior (p < 0.05) to placebo in 3 of the 4 primary endpoints (disease activity assessed by the investigator, disease activity assessed by the patient, and reduction of the number of tender/painful joints). No difference was observed regarding number of swollen joints. The difference between meloxicam 7.5 mg once daily and placebo reached statistical significance in 2 of the 4 primary endpoints, disease activity assessed by the patient and number of tender/painful joints. A statistically significant difference between meloxicam 1.5 mg and 7.5 mg was not observed for any primary endpoint. The rating of global tolerance by investigators and patients at the end of the study was similar in the 3 treatment groups, indicating that meloxicam and placebo were generally similarly well tolerated. However, there was a slightly higher incidence of gastrointestinal (GI) disturbances reported by patients receiving meloxicam 15 mg. GI adverse events were reported by 11, 11, and 16% of patients in the placebo, meloxicam 7.5 mg, and meloxicam 15 mg groups, respectively. None were serious. CONCLUSION: Meloxicam in daily doses of 7.5 and 15 mg is effective in treating the signs and symptoms of RA.

Aged↗
PubMed1996

Meloxicam: influence on arachidonic acid metabolism. Part II. In vivo findings.

Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) derived from enolic acid. Preclinical studies have indicated that meloxicam has potent anti-inflammatory activity, together with a good gastrointestinal and renal tolerability profile. This report summarizes studies undertaken to compare meloxicam to other NSAIDs in the inhibition of the inducible cyclooxygenase (COX-2) in inflamed areas (pleurisy of the rat, peritonitis of mice) and their influence on the activity of the constitutive cyclooxygenase (COX-1) in stomach, kidney, brain, and blood. In pleurisy of the rat, meloxicam was twice as potent as tenoxicam, 3 times as potent as flurbiprofen, 8 times as potent as diclofenac, and 20 times as potent as tenidap at inhibiting prostaglandin E2 (PGE2) biosynthesis. In the peritonitis model in mice, meloxicam was approximately twice as active as piroxicam, and more than 10 times as active as diclofenac in the suppression of PGE biosynthesis. Doses of meloxicam sufficient to inhibit PGE2 biosynthesis in the pleural exudate and peritoneal exudate had no influence on leukotriene-B4 (LTB4) or leukotriene-C4 (LTC4) content. The effect of meloxicam on the PGE2 content of rat gastric juice and rat urine was weaker than that of piroxicam or diclofenac. Meloxicam was a weaker inhibitor of the increased PGE2 concentration in brain of rats and mice (induced by convulsant doses of pentetrazole) than piroxicam, diclofenac, or indomethacin. Meloxicam had a weaker effect on serum thromboxane-B2 (TXB2) concentration in rats than piroxicam or tenoxicam. The in vivo findings confirm the results of in vitro tests, conducted separately, showing that meloxicam preferentially inhibits COX-2 over COX-1. COX-2 is the inducible isoenzyme implicated in the inflammatory response, whereas COX-1 has cytoprotective effects in the gastric mucosa. Therefore, a preferential selectivity for one isoenzyme over another, as displayed by meloxicam, may have implications in the clinical setting in terms of a more favorable risk: benefit profile.

Administration, Oral↗
PubMed1998

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.

SELECT is a large-scale, prospective, international, multicentre, double-blind, double-dummy, randomized, parallel-group trial. Patients with exacerbation of osteoarthritis were treated with the recommended dose of meloxicam (7.5 mg) or piroxicam (20 mg) once daily for 28 days; 4320 patients were administered meloxicam and 4336 piroxicam. The incidence of adverse events was significantly lower in the meloxicam group (22.5%) compared with the piroxicam group (27.9%; P < 0.001), mainly due to the significantly lower incidence of gastrointestinal (GI) adverse events in the meloxicam than in the piroxicam group (10.3% vs 15.4%,; P < 0.001), while the efficacy of both drugs was equivalent. Individual GI events occurred significantly less often with meloxicam than piroxicam: dyspepsia (3.4% vs 5.8%; P < 0.001), nausea/vomiting (2.5% vs 3.4%; P < 0.05) and abdominal pain (2.1% vs 3.6%; P < 0.001). There were 16 patients with perforations, ulcerations or bleeding (PUBs) of the upper GI tract in the piroxicam group compared with seven in the meloxicam group (relative risk piroxicam:meloxicam = 1.4). Four PUBs were complicated (perforations or bleedings); none of these occurred in the meloxicam group (relative risk piroxicam:meloxicam = 1.9). The outcome of SELECT is consistent with that of the large-scale clinical trial of similar design and size which compared 7.5 mg meloxicam with 100 mg diclofenac in patients with osteoarthritis, and with a previous global analysis of the safety of meloxicam. It adds further data to the proposed relationship between selective inhibition of cyclooxygenase-2 and improved GI tolerability of non-steroidal anti-inflammatory drugs.

Aged↗
PubMed1998

Antinociceptive effect of meloxicam, in neurogenic and inflammatory nociceptive models in mice.

OBJECTIVE: The antinociceptive effect of the new cyclooxygenase (COX)-2 inhibitor, meloxicam, given intraperitoneally (i.p.), was assessed in different models of chemical and thermal nociception in mice. MATERIAL AND METHODS: The analgesic effect was analysed using acetic acid-induced abdominal constriction (AA), formalin and capsaicin-induced licking, and hot-plate tests. RESULTS: The treatment of animals with meloxicam or diclofenac (2.8-94.3 micromol/kg, i.p. 30 min prior) caused graded and significant inhibition of AA, with mean ID50 values of 7.4 and 38.0 micromol/kg, respectively. At the ID50 level, meloxicam was about 5-fold more potent than diclofenac. In the formalin test, meloxicam or diclofenac (0.8-94.3 micromol/kg, i.p. 30 min prior) also caused significant inhibition of both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking. The calculated mean ID50 values for the early phase were: 7.1 and > 94.3 micromol/kg, while for the late phase they were 2.8 and 34.5 micromol/kg, respectively, for meloxicam and diclofenac. Meloxicam also caused significant inhibition of formalin-induced oedema (p < 0.05). Meloxicam and diclofenac (0.8-314.4 micromol/kg, i.p. 30min prior) produced significant and dose-related inhibition of neurogenic nociception caused by topical injection of capsaicin, with mean ID50 values of 4.0 and 47.4 micromol/kg, respectively, but were ineffective in the hot-plate model of nociception. CONCLUSIONS: The present study shows that meloxicam dose-dependently exhibited systemic antinociceptive action when assessed against neurogenic and inflammatory pain caused by acetic acid, formalin and capsaicin models. In contrast, when assessed in the hot-plate test, meloxicam had no significant effect. Thus, meloxicam and other COX-2 inhibitors might be useful for therapeutic intervention in the management of neurogenic and inflammatory pain.

Abdominal Muscles↗
PubMed2000

Steady-state pharmacokinetics of lithium in healthy volunteers receiving concomitant meloxicam.

AIMS: This open, controlled study investigated the effect of concomitant 15 mg oral meloxicam on the pharmacokinetics of lithium in healthy male volunteers. METHODS: On days 1-14 lithium was coadministered with meloxicam to 16 volunteers; on days 10-14 lithium was administered in individualized dosage regimes to achieve stable lithium plasma concentrations in the lower therapeutic range of 0.3-0.7 mmol l(-1). A 12 h steady-state concentration profile for lithium was obtained at day 14, after which meloxicam was withdrawn. The lithium dose remained unchanged from day 15 to day 22, at which time a second lithium concentration profile was determined. RESULTS: Lithium and meloxicam were well tolerated throughout the study and all 16 volunteers completed the study. Lithium predose concentrations (Cpre,ss) and area under the curve (AUCss) values both increased by 21% (paired t-test P = 0.0002; 90% confidence intervals for test/reference ratios: 113-130% and 115-128%, respectively) when lithium was coadministered with meloxicam compared with values obtained for lithium alone. The geometric mean lithium Cpre,ss was 0.65 mmol l(-1) when coadministered with meloxicam and 0.54 mmol l(-1) for lithium alone. Lithium Cmax,ss values were increased by 16% by coadministration of meloxicam, from 0.97 mmol l(-1) to 1.12 mmol l(-1). The total plasma clearance of lithium was lower with concomitant meloxicam administration (82.5% of value for lithium alone). CONCLUSIONS: Meloxicam (15 mg) moderately increased the plasma concentration of lithium in healthy volunteers, but by a magnitude thought to be of low clinical relevance. Nevertheless, lithium plasma concentrations should be closely monitored in patients receiving concomitant meloxicam and lithium therapy.

Adult↗
PubMed1997

Meloxicam pharmacokinetics in renal impairment.

AIMS: The aim of the present study was to determine how the pharmacokinetics of meloxicam are affected by kidney dysfunction and consequently to define the appropriate dose for the use of meloxicam in patients with mild or moderate renal impairment. METHODS: Meloxicam was administered to subjects with mild (creatinine clearance 41-60 ml min-1) to moderate (20-40 ml min-1) renal impairment compared with normal renal function (> 60 ml min-1). Thirty-eight subjects received meloxicam 15 mg once daily over 9 days. Meloxicam plasma concentrations were determined from blood samples taken during the study and pharmacokinetic parameters calculated according to noncompartmental methods. RESULTS: Subjects with no or mild renal impairment showed similar pharmacokinetic profiles (geometric mean AUCSS (%gCV) 55 (33%) vs 55 (38%) micrograms ml-1 h). Subjects with moderate renal impairment demonstrated lower total plasma meloxicam concentrations (AUCSS 35 (50%) micrograms ml-1 h, with corresponding higher plasma clearance (P = 0.013) compared with subjects with no renal impairment. However, this was combined with higher meloxicam free fractions in moderately impaired subjects such that free meloxicam concentrations were similar in all three groups. Meloxicam was well tolerated with few adverse events occurring and no difference in incidence observable between groups. CONCLUSIONS: On the basis of these results there is no necessity for a dosage adjustment when administering meloxicam to patients with mild to moderate renal impairment.

Administration, Oral↗
PubMed1999

Activation of human cytochrome P-450 3A4-catalyzed meloxicam 5'-methylhydroxylation by quinidine and hydroquinidine in vitro.

In humans, meloxicam is metabolized mainly by cytochrome P-450 (CYP)-dependent hydroxylation of the 5'-methyl group. The predominant P-450 enzyme involved in meloxicam metabolism is CYP 2C9, with a minor contribution of CYP 3A4. Quinidine, a CYP 3A4 substrate commonly used as a selective in vitro inhibitor of CYP 2D6, was found to markedly increase the rate of meloxicam hydroxylation during in vitro experiments with human liver microsomes. A similar activation was observed with other compounds that are structurally related to quinidine. Besides quinidine, quinine and hydroquinidine were the most potent activators of meloxicam hydroxylation. Using expressed cytochrome P-450 enzymes and selective chemical inhibitors of CYP 2C9 and CYP 3A4, it was found that quinidine markedly increased the rate of CYP 3A4-mediated meloxicam hydroxylation but was virtually without effect on CYP 2C9. Kinetic analysis was performed to obtain insight into the possible mechanism of activation of CYP 3A4 and into the mutual interaction of quinidine/hydroquinidine and meloxicam. Quinidine and hydroquinidine decreased Km and increased Vmax of meloxicam hydroxylation, which was consistent with a mixed-type nonessential activation. Meloxicam, in turn, decreased both Km and Vmax of quinidine metabolism by CYP 3A4, indicating an uncompetitive inhibition mechanism. These results support the assumption that CYP 3A4 possesses at least two different substrate-binding sites. A clinically relevant effect on meloxicam drug therapy is not expected, because the most likely outcome in practice is moderately decreased meloxicam plasma concentrations.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1996

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.

The pharmacodynamic properties of meloxicam, a new nonsteroidal antiinflammatory drug (NSAID), that go beyond those typical of an NSAID were examined. The extent to which meloxican shows NSAID-like interactions with paracetamol, pirenzepine, chlorthalidone, phenprocoumon and tolbutamide was also investigated. In the dose range studied, meloxicam had no influence on the blood pressure of the unanaesthetized rat, blood flow, heart rate, ECG and respiratory minute volume of the anaesthetized cat or on the blood pressure, heart rate and respiratory minute volume of the anaesthetized dog. The acute toxicity level of meloxicam after oral and parenteral administration to the rat and mouse proved considerably lower than that of indomethacin. Meloxicam showed excellent tissue tolerability following parenteral administration. The effects against inflammatory pain and acute antiexudative effects of meloxicam were enhanced by simultaneous low doses of paracetamol. Pirenzepine showed an antagonistic effect on the ulcerogenicity of meloxicam in the rat stomach. The diuretic effect of chlorthalidone in the rat was not influenced by high doses of meloxicam. The effect of phenprocoumon in the rat was enhanced by high doses of meloxicam. However, the hypoglycaemic effect of tolbutamide in the rabbit was not influenced by meloxicam.

Acetaminophen↗
PubMed1997

Meloxicam: selective COX-2 inhibition in clinical practice.

Nonsteroidal antiinflammatory drugs (NSAIDs) exert their actions by inhibiting cyclooxygenase (COX). It has recently been postulated that NSAIDs' antiinflammatory efficacy arises from inhibition of the COX-2 isoform of cyclooxygenase, whereas inhibition of the COX-1 isoform produces the troublesome and sometimes serious gastric and renal side effects of NSAIDs. A relatively selective COX-2 inhibitor, such as meloxicam, may combine antiinflammatory efficacy with improved tolerability. In volunteers, indomethacin 75 mg, but not meloxicam 7.5 mg, inhibited renal prostaglandin E2 excretion and platelet aggregation (COX-1 mediated effects). Double-blind, randomized trials in osteoarthritis and rheumatoid arthritis patients have shown equivalent antiinflammatory efficacy among meloxicam 7.5 mg or 15 mg and diclofenac 100 mg, naproxen 750 mg, and piroxicam 20 mg. In a double-blind, placebo-controlled trial, meloxicam (7.5 or 15 mg) caused less endoscopically detected gastrointestinal (GI) damage (Lanza scale) than piroxicam 20 mg. The MELISSA study, a double-blind, randomized, 28-day trial in over 9,000 patients showed that meloxicam 7.5 mg caused statistically less total GI toxicity, dyspepsia, abdominal pain, nausea and vomiting, and diarrhea than diclofenac 100 mg, despite equivalent reductions in pain on movement for each treatment. A global safety analysis of clinical trials, representing over 5,600 patients and comprising 170 and 1,100 patient-years of exposure for meloxicam 7.5 mg and 15 mg, respectively, showed that meloxicam caused less GI toxicity and fewer peptic ulcers and GI bleeds than naproxen, diclofenac, or piroxicam. The renal safety profile and incidence of liver function abnormalities with meloxicam is equivalent to other NSAIDs available for clinical use. In conclusion, relatively selective COX-2 inhibition exemplified by meloxicam may offer effective symptom relief with an improved GI tolerability profile.

Animals↗
PubMed1997

An evaluation of the interaction of meloxicam with frusemide in patients with compensated chronic cardiac failure.

AIMS: To evaluate the interaction of meloxicam with frusemide in patients with compensated cardiac failure. METHODS: Nineteen patients with Grade II or III compensated chronic cardiac failure completed this randomized, double-blind, cross-over study. The patients received 40 mg frusemide day(-1) for 7 days. Thereafter, patients received either 15 mg meloxicam plus 40 mg frusemide day(-1), or one placebo tablet plus 40 mg frusemide day(-1) for 7 days. After a washout period of 7 days during which patients received 40 mg frusemide day(-1) for 7 days, the patients were crossed over to the alternate treatment. The effect of concomitant ingestion of meloxicam and frusemide on frusemide-induced diuresis, urine and serum electrolytes, urinary frusemide excretion, and plasma frusemide pharmacokinetics was also determined. RESULTS: The estimate (90% confidence interval) of the '(frusemide + meloxicam)/(frusemide alone)' mean ratio of the variables Cmax, AUC(SS) and Cmax/AUC(SS) for plasma frusemide were 121% (101% to 145%), 106% (96.4% to 117%), and 114% (98.3% to 132%), respectively. Similarly, the estimate (90% confidence interval) of the '(frusemide + meloxicam)/(frusemide alone)' of the mean ratio of the variable cumulative urinary frusemide excretion after multiple doses of frusemide were 123% (101% to 150%) for the period 0-8 h, and 122% (105% to 142%) for the period 0-24 h after drug administration on day 7. The estimate (90% confidence interval) of the '(frusemide + meloxicam)/(frusemide alone)' mean ratio of the pharmacodynamic variables cumulative sodium excretion was 105% (95.2% to 116%) for the period 0-8 h and 108% (96.5% to 121%) for the period 0-24 h after drug administration on day 7. CONCLUSIONS: Meloxicam may lead to slightly increased maximum concentrations of frusemide in plasma, as well as to slightly increased urinary excretion of frusemide, without affecting the pharmacodynamics of frusemide. Thus there is no clinically significant pharmacokinetic or pharmacodynamic interaction of meloxicam with frusemide following repeated co-administration of meloxicam and frusemide to patients with compensated chronic cardiac failure.

Aged↗
PubMed1996

A six-month double-blind trial to compare the efficacy and safety of meloxicam 7.5 mg daily and naproxen 750 mg daily in patients with rheumatoid arthritis.

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which preferentially inhibits cyclooxygenase-2 over cyclooxygenase-1. A double-blind parallel-group trial compared meloxicam 7.5 mg once daily (n = 199) with naproxen 750 mg (n = 180) in rheumatoid arthritis. There was no significant difference between the groups regarding the primary efficacy variables (global efficacy assessment by patient and investigator, number of painful/tender and swollen joints) and eight of the ten secondary efficacy endpoints. Only the swollen joint severity index and the number of discontinuations due to lack of efficacy favoured naproxen 750 mg significantly over meloxicam 7.5 mg. Meloxicam was better tolerated in the gastrointestinal (GI) tract, with fewer GI adverse events in the meloxicam-treated group (30.3%) than in the naproxen-treated group (44.7%), where two patients developed ulcers. No ulcers were seen in meloxicam patients. Significantly more patients discontinued due to GI adverse events in the naproxen group. Additionally, there was a significant decrease in haemoglobin and a significant increase in serum creatinine and urea in the naproxen group compared with the meloxicam group. In conclusion, meloxicam 7.5 mg once daily is a promising treatment in rheumatoid arthritis, with efficacy comparable to naproxen 750 mg. Meloxicam has the advantage of a significantly lower incidence of GI and renal side effects.

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