Movalis scientific update |
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Clin Exp Pharmacol Physiol. 2006 Oct;33(10):917-24.
Harirforoosh S, Aghazadeh-Habashi A, Jamali F.
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
Extent of renal effect of cyclo-oxygenase-2-selective inhibitors is pharmacokinetic dependent.
1. Non-steroidal anti-inflammatory drugs (NSAIDs) cause renal side-effects. In the present study, we tested the hypothesis that the extent of the renal effects of cyclo-oxygenase (COX)-2-selective NSAIDs is linked to their pharmacokinetics. 2. A single oral dose of rofecoxib (10 mg/kg), celecoxib (40 mg/kg), meloxicam (3 mg/kg) or placebo was administered to rats. Urinary excretion of electrolytes, a marker of renal effects, and plasma and kidney concentrations of NSAIDs were measured. Rofecoxib and celecoxib, but not meloxicam, significantly decreased urinary sodium and potassium excretion. There was a significant correlation between the area under the 24 h plasma concentration-time curve (AUC(0-24)) of rofecoxib and the change in sodium (r = -0.65; P < 0.02) and potassium (r = -0.82; P < 0.0006) excretion. The AUC(0-24) of celecoxib was correlated with sodium (r = -0.80; P < 0.05) but not potassium excretion. The ratios of kidney to plasma drug concentrations were 1.72, 3.16 and 0.17 for rofecoxib, celecoxib and meloxicam, respectively. 3. The renal effect of the COX-2-selective NSAIDs examined, marked by their ability to reduce the excretion of electrolytes, is influenced by systemic exposure to the drugs. The relatively higher distribution into the kidneys of rofecoxib and celecoxib compared with meloxicam suggests involvement of direct drug exposure in the kidneys in the adverse renal effect.
Clin Gastroenterol Hepatol. 2005 May;3(5):489-98.
Rostom A, Goldkind L, Laine L.
University of Ottawa, Ontario, Canada.
Nonsteroidal anti-inflammatory drugs and hepatic toxicity: a systematic review of randomized controlled trials in arthritis patients.
BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) might cause hepatic side effects, but the frequency of these laboratory and clinical side effects is uncertain. METHODS: Searches of bibliographic databases MEDLINE and EMBASE and of public archives of the Food and Drug Administration were conducted to identify randomized controlled trials of diclofenac, naproxen, ibuprofen, celecoxib, rofecoxib, valdecoxib, or meloxicam in adults with osteoarthritis or rheumatoid arthritis that provided information on aminotransferase elevations >3 x upper limit of normal, liver-related discontinuations, hepatic serious adverse events, liver-related hospitalizations, or liver-related deaths. The proportion of patients with each of the hepatic toxicity outcomes was calculated separately by using sample size weighted pooling for each NSAID. RESULTS: Sixty-seven articles from the bibliographic database and 65 studies from the Food and Drug Administration archives met inclusion criteria. Diclofenac (3.55%; 95% confidence interval [CI], 3.12%-4.03%) and rofecoxib (1.80%; 95% CI, 1.52%-2.13%) had higher rates of aminotransferase >3 x upper limit of normal than placebo (0.29; 95% CI, 0.17-0.51) and the other NSAIDs (all < or = 0.43%). The 95% CIs for liver-related discontinuations of all NSAIDs except diclofenac (2.17%; 95% CI, 1.78%-2.64%) overlapped with placebo. Only 1 liver-related hospitalization (among 37,671 patients) and 1 liver-related death (among 51,942 patients) occurred, with naproxen. CONCLUSIONS: Diclofenac and rofecoxib had higher rates of aminotransferase elevations than placebo and other NSAIDs studied. No NSAID studied had increased rates of liver-related serious adverse events, hospitalizations, or deaths.
Expert Opin Pharmacother. 2005 Oct;6(12):2117-40.
Gates BJ, Nguyen TT, Setter SM, Davies NM.
College of Pharmacy, Department of Pharmaceutical Sciences, Washington State University, Pullman, Washington 99164-6534, USA.
Meloxicam: a reappraisal of pharmacokinetics, efficacy and safety.
The discovery of two distinct isoenzymes of COX has led to the development and clinical introduction of COX-2 inhibitors with increased selectivity onto the market. Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class, and is a preferential inhibitor of COX-2, demonstrating effectiveness with anti-inflammatory, analgesic and antipyretic activity. Meloxicam is therapeutically utilised in the management of osteoarthritis and rheumatoid arthritis. Trials have examined the risk of gastrointestinal ulceration of meloxicam when compared with traditional non-specific COX-inhibiting NSAIDs with mixed results; meloxicam seems to have a greater gastrointestinal risk than the highly specific COX-2 NSAIDs. Meloxicam has a plasma half-life of approximately 20 h and is convenient for once daily administration. Neither moderate renal nor hepatic insufficiency significantly alters the pharmacokinetics of meloxicam in short-term studies. Furthermore, dose adjustment is not required in the elderly. Recent drug-drug interaction studies have demonstrated that meloxicam interacts with some medications, including cholestyramine, lithium and some inhibitors of cytochrome P450 -2C9 and -3A4. Consequently, increased clinical vigilance should be maintained when coprescribing some medications with meloxicam. Concentration-dependent therapeutic and toxicological effects have yet to be extensively elucidated for meloxicam. Long-term safety in various organ systems, especially in the heart and vascular system and with concomitant drug administration, remains to be proven. The pharmacokinetics of meloxicam enables once daily application, which increases compliance compared with some shorter acting NSAIDs; however, long-term clinical data clearly demonstrating safety and efficacy advantages are lacking.
Zh Nevrol Psikhiatr Im S S Korsakova. 2005;105(7):33-7
[No authors listed]
[Article in Russian]
[Efficacy of movalis in the treatment of acute low back pains]
The main aim of the study was a search for factors influencing efficacy of movalis used in combined form, injection and tablets, for the treatment of patients with acute back pain syndrome (BPS) and evaluation of the drug safety. Thirty patients, 18 female, 12 male, mean age 43.1 years, with primary BPS have been studied. In 83% of patients, BPS was caused by muscle tonic syndrome and in 17% the latter was combined with radiculopathy. Meloxicam therapy was conducted using intramuscular injections of 15 mg daily during 5 days with following oral drug intake (1 tablet daily). Treatment duration was 2 weeks. This treatment regime proved to be highly effective. The subjective meloxicam efficacy was the following: moderate--7%; good--30%; very good--33%; excellent--30%. Side effects, such as transient stomach pain, was observed only in 6.6% of patients. The main factors reducing meloxicam efficacy were affective disorders, namely, a level of depression and anxiety, and radiculopathy.
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Drug category:Antirheumatic
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