Movalis scientific update |
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2010 Jun 1;33(3):277-86.
Lehr T, Narbe R, Jöns O, Kloft C, Staab A.
Department of Clinical Pharmacy, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany.
Population pharmacokinetic modelling and simulation of single and multiple dose administration of meloxicam in cats.
The objectives of these investigations were: first, to describe the pharmacokinetic properties of meloxicam in cats following single and multiple oral administration and secondly, to simulate different oral dosage regimes for meloxicam in cats after multiple dose administration to illustrate and evaluate those dosage regimes for the alleviation of inflammation and pain in cats. Six healthy domestic short hair cats were treated orally with various dosage regimes (0.05-0.2 mg/kg/day). Plasma samples were collected at predefined times and quantitatively analysed using liquid/liquid extraction followed by reverse phase HPLC with UV-detection. Meloxicam plasma concentration data were analysed using the population pharmacokinetic approach (software: NONMEM). The final model was used to simulate different dosage regimes. The plasma concentration-time profiles of meloxicam in cats after oral single and multiple dose administration were best described by an open one-compartment model with first-order absorption and first-order elimination. Pharmacokinetic parameters were estimated to be 0.00656 L/h/kg for the total apparent body clearance (CL/F), 0.245 L/kg for the apparent volume of distribution (V/F), 1.26 1/h for the absorption constant (K(A)) and 25.7 h for the mean plasma terminal half-life. Simulations showed that the median trough steady-state concentrations of 228 ng/mL were reached after five, one or 6 days following a single initial dose of 0.05, 0.1 and 0.2 mg/kg each followed by 0.05 mg/kg/day.
2010 Jun 2. [Epub ahead of print]
Buduneli N, Buduneli E, Cetin EO, Kırılmaz L, Kütükçüler N.
Ege University, School of Dentistry, Department of Periodontology, 35100 Bornova, Izmir, Turkey +90 323 388 1105 ; +90 232 388 0325 ; nurcan.buduneli@ege.edu.tr.
Clinical findings and gingival crevicular fluid prostaglandin E2 and interleukin-1-beta levels following initial periodontal treatment and short-term meloxicam administration.
Objective: To evaluate the effects of adjunctive meloxicam administration on clinical periodontal measurements and gingival crevicular fluid (GCF) prostaglandin E(2) (PGE(2)) and interleukin-1-beta (IL-1beta) levels in chronic periodontitis. Methods: Forty chronic periodontitis patients were randomized to receive either meloxicam 7.5 mg or placebo tablets for 10 days with scaling and root planing (SRP). GCF levels of PGE(2) and IL-1beta at baseline, day 10 of drug intake and 4 weeks after SRP were determined by enzyme-linked immunosorbent assay. Demographic, clinical periodontal data were analyzed using a repeated measures ANOVA and Bonferroni analysis. GCF PGE(2) and IL-1beta levels were compared between different evaluation times using the Friedman test. The Mann-Whitney test was used to compare biochemical data between the study groups. Pearson correlation analysis was used to relate clinical and biochemical data. Results: Study groups showed significant reductions in all clinical periodontal measurements and GCF volume (p < 0.05). In both groups, IL-1beta was reduced significantly on day 10 and at week 4 compared with baseline (p < 0.01) without significant changes in PGE(2) levels (p > 0.05). No significant differences were found between study groups in GCF IL-1beta or PGE(2) levels (p > 0.05). Conclusion: Adjunctive meloxicam does not seem to provide additional improvement in clinical parameters or GCF PGE(2) and IL-1beta levels. Larger-scale studies may better clarify potential usage of anti-inflammatory agents in periodontal therapy.
2010 Apr;33(2):118-31.
Schmid VB, Spreng DE, Seewald W, Jung M, Lees P, King JN.
Novartis Centre de Recherche Santé Animale SA, St-Aubin, Switzerland. vincent.schmid@novartis.com
Analgesic and anti-inflammatory actions of robenacoxib in acute joint inflammation in dog.
The objectives of this study were to establish dose-response and blood concentration-response relationships for robenacoxib, a novel nonsteroidal anti-inflammatory drug with selectivity for inhibition of the cyclooxygenase (COX)-2 isoenzyme, in a canine model of synovitis. Acute synovitis of the stifle joint was induced by intra-articular injection of sodium urate crystals. Robenacoxib (0.25, 0.5, 1.0, 2.0 and 4.0 mg/kg), placebo and meloxicam (0.2 mg/kg) were administered subcutaneously (s.c.) 3 h after the urate crystals. Pharmacodynamic endpoints included data from forceplate analyses, clinical orthopaedic examinations and time course of inhibition of COX-1 and COX-2 in ex vivo whole blood assays. Blood was collected for pharmacokinetics. Robenacoxib produced dose-related improvement in weight-bearing, pain and swelling as assessed objectively by forceplate analysis (estimated ED(50) was 1.23 mg/kg for z peak force) and subjectively by clinical orthopaedic assessments. The analgesic and anti-inflammatory effects of robenacoxib were significantly superior to placebo (0.25-4 mg/kg robenacoxib) and were non-inferior to meloxicam (0.5-4 mg/kg robenacoxib). All dosages of robenacoxib produced significant dose-related inhibition of COX-2 (estimated ED(50) was 0.52 mg/kg) but no inhibition of COX-1. At a dosage of 1-2 mg/kg administered s.c., robenacoxib should be at least as effective as 0.2 mg/kg of meloxicam in suppressing acute joint pain and inflammation in dogs.
2010 May;12(5):412-7.
Tan C, Allan GS, Barfield D, Krockenberger MB, Howlett R, Malik R.
Double Bay Veterinary Clinic, 125 Manning Road, Woollahra, NSW 2025, Australia.
Synovial osteochondroma involving the elbow of a cat.
CLINICAL PRESENTATION: A 12-year-old spayed domestic crossbred cat presented because she would not walk down stairs. A firm swelling on the medial aspect of the elbow was detected during physical examination. The lesion was not hot or painful on palpation and the lameness was mild, but the elbow had a reduced range of motion compared with the contralateral limb. DIAGNOSIS AND TREATMENT: Plain radiographs, physical findings, the appearance of the lesion at surgery and histopathological examination of biopsy specimens suggested the mass was a synovial osteochondroma arising from synovial membrane near the medial portion of the elbow joint. Resection of the lesion improved the cat's mobility and overall clinical status. At the time of writing, the cat continued to do well 18 months following surgery and was receiving standard doses of meloxicam for the concurrent elbow osteoarthritis. PRACTICAL RELEVANCE: Practitioners should be alert to the possibility of this benign entity. Misdiagnosis as a chondrosarcoma, for example, might conceivably lead to radical and unnecessary amputation. Copyright 2010 Elsevier Ltd. All rights reserved
2010 Jun 1;77(2):496-501. Epub 2010 Mar 28.
Crook J, Patil N, Wallace K, Borg J, Zhou D, Ma C, Pond G.
Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
A phase III randomized trial of the timing of meloxicam with iodine-125 prostate brachytherapy.
PURPOSE: Nonsteroidal anti-inflammatory medication is used to reduce prostate edema and urinary symptoms following prostate brachytherapy. We hypothesized that a cyclooxygenase-2 (COX-2) inhibitor regimen started 1 week prior to seed implant might diminish the inflammatory response, thus reducing edema, retention rates, and symptom severity. METHODS AND MATERIALS: From March 2004 to February 2008, 316 men consented to an institutional review board-approved randomized study of a 4-week course of meloxicam, 7.5 mg orally twice per day, starting either on the day of implant or 1 week prior to implant. Brachytherapy was performed using iodine-125 seeds and was preplanned and performed under transrectal ultrasound (TRUS) and fluoroscopic guidance. Prostate volume obtained by MR imaging at 1 month was compared to baseline prostate volume obtained by TRUS planimetry and expressed as an edema factor. The trial endpoints were prostate edema at 1 month, International Prostate Symptom Score (IPSS) questionnaire results at 1 and 3 months, and any need for catheterization. RESULTS: Results for 300 men were analyzed. Median age was 61 (range, 45-79 years), and median TRUS prostate volume was 35.7 cc (range, 18.1-69.5 cc). Median IPSS at baseline was 5 (range, 0-24) and was 15 at 1 month, 16 at 3 months, and 10 at 6 months. Catheterization was required for 7% of patients (6.2% day 0 arm vs. 7.9% day -7 arm; p = 0.65). The median edema factor at 1 month was 1.02 (range, 0.73-1.7). 1.01 day 0 arm vs. 1.05 day -7 arm. Baseline prostate volume remained the primary predictor of postimplant urinary retention. CONCLUSIONS: Starting meloxicam 1 week prior to brachytherapy compared to starting immediately after the procedure did not reduce 1-month edema, improve IPSSs at 1 or 3 months, or reduce the need for catheterization. Copyright 2010 Elsevier Inc. All rights reserved.
2009 Oct 7;(4):CD007552.
Moore RA, Derry S, McQuay HJ.
Pain Research and Nuffield Department of Anaesthetics, University of Oxford, West Wing (Level 6), John Radcliffe Hospital, Oxford, Oxfordshire, UK, OX3 9DU.
Single dose oral meloxicam for acute postoperative pain in adults.
BACKGROUND: Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) used mainly in treating pain associated with arthritis. The usual oral dose for osteoarthritis is 15 mg daily, but lower doses of 7.5 mg are advised in older patients. This review sought to evaluate the efficacy and safety of oral meloxicam in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties. OBJECTIVES: To assess the efficacy of single dose oral meloxicam in acute postoperative pain, and any associated adverse events. SEARCH STRATEGY: We searched Cochrane CENTRAL (Issue 2, 2009), MEDLINE (June 2009); EMBASE (June 2009); the Oxford Pain Relief Database. SELECTION CRITERIA: Randomised, double-blind, placebo-controlled clinical trials of oral meloxicam for relief of acute postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We planned to use area under the "pain relief versus time" curve to derive the proportion of participants with meloxicam experiencing least 50% pain relief over 4 to 6 hours, using validated equations; to use number needed to treat to benefit (NNT); the proportion of participants using rescue analgesia over a specified time period; time to use of rescue analgesia; information on adverse events and withdrawals. MAIN RESULTS: No studies were identified by the searches that examined oral meloxicam in patients with established postoperative pain. AUTHORS' CONCLUSIONS: In the absence of evidence of efficacy, at present, for oral meloxicam in acute postoperative pain, its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes, there is no urgent research agenda.
2009 Dec;40(4):601-6.
Carpenter JW, Pollock CG, Koch DE, Hunter RP.
Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506, USA.
Single and multiple-dose pharmacokinetics of meloxicam after oral administration to the rabbit (Oryctolagus cuniculus).
The nonsteroidal anti-inflammatory drug (NSAID) meloxicam is a very popular anti-inflammatory, analgesic, and antipyretic agent used in veterinary medicine. To determine the pharmacokinetics of this NSAID in rabbits following a single dose and 10-day period of dosing, eight clinically normal, 8-mo-old New Zealand white rabbits (Oryctolagus cuniculus) were administered 0.2 mg/kg meloxicam p.o. daily. Pharmacokinetic analysis of the meloxicam was determined via noncompartmental analysis. After oral administration, mean +/- standard deviation values for area under the curve were 1.8 +/- 0.50 and 2.1 +/- 0.55 microg x h/ml, and maximum plasma concentrations were 0.17 +/- 0.06 and 0.24 +/- 0.07 microg/ml for Day 1 and Day 10, respectively. The half-life was approximately 8 hr. Administration of meloxicam at a dosage of 0.2 to 0.3 mg/kg p.o. every 24 hr is suggested. Although a higher dose may be required for optimum effects, this would require efficacy and safety studies in this species. Meloxicam administered at 0.2 mg/kg p.o. daily for 10 day was well tolerated by the rabbits
2009 Sep;41(7):693-9.
de Grauw JC, van de Lest CH, Brama PA, Rambags BP, van Weeren PR.
Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
In vivo effects of meloxicam on inflammatory mediators, MMP activity and cartilage biomarkers in equine joints with acute synovitis.
REASONS FOR PERFORMING STUDY: Meloxicam is a commonly used nonsteroidal anti-inflammatory drug in equine practice, but little is known about its in vivo effects on joint inflammation and cartilage turnover. OBJECTIVES: To study the effects of meloxicam on biomarkers of inflammation, matrix metalloproteinase (MMP) activity, and cartilage biomarkers in joints with experimental synovitis. METHODS: In a 2-period cross-over study, synovitis was induced at T = 0 h in the L or R intercarpal joint of 6 horses by intraarticular injection of 0.5 ng lipopolysaccharide (LPS). Horses received once daily meloxicam (0.6 mg/kg bwt per os) or placebo starting at post injection hour (PIH) 2, and clinical evaluations as well as blood and synovial fluid (SF) sampling were performed at PIH 0, 8, 24 and 168. Synovial fluid was analysed for prostaglandin E2, bradykinin, substance P, general MMP activity, glycosaminoglycans (GAG), CS846 epitope, type II collagen cleavage fragments (C2C) and type II collagen carboxypropeptide (CPII). Concentrations in meloxicam- vs. placebo-treated joints over time were compared using a linear mixed model. RESULTS: Lipopolysaccharide injection caused marked transient synovitis without systemic effects. Meloxicam caused a significant reduction in lameness at PIH 8 and 24 and tended to reduce effusion. In addition, meloxicam significantly suppressed SF prostaglandin E2 and substance P release at PIH 8 and bradykinin at PIH 24 compared to placebo treatment. General MMP activity at PIH 8 and 24 was significantly lower in meloxicam- vs. placebo-treated joints, as were GAG, C2C and CPII concentrations at PIH 24. CONCLUSIONS: Acute transient synovitis leads to substantial increases in SF biomarkers of inflammation, MMP activity and cartilage turnover, which can be significantly suppressed by meloxicam. POTENTIAL RELEVANCE: Early oral treatment with meloxicam ameliorates not only clinical signs and joint inflammation in acute synovitis, but may also limit inflammation-induced cartilage catabolism.
2009 Dec;11(12):997-1004. Epub 2009 Nov 11.
Bennett D, Morton C.
Institute of Comparative Medicine, Division of Companion Animal Studies, University of Glasgow Veterinary Faculty, Bearsden Road, Bearsden, Glasgow G61 1 QH, United Kingdom. D.Bennett@vet.gla.ac.uk
A study of owner observed behavioural and lifestyle changes in cats with musculoskeletal disease before and after analgesic therapy.
This study describes the use of a simple questionnaire-based tool to identify behavioural/lifestyle changes that are associated with chronic pain in the cat. These changes were grouped into four behavioural domains (mobility, activity, grooming and temperament). Twenty-three cats with chronic musculoskeletal pain as determined by clinical examination were included. The owners of these cats were asked to complete a questionnaire before and 28 days after the start of analgesic treatment (meloxicam). This included a global assessment of changes in behaviour and assessment of the degree of behavioural change observed within each of the defined domains. The attending veterinary surgeon was independently asked to provide a global score before and after treatment. Both owners and veterinary surgeons reported significant changes in behaviour/lifestyle after analgesic therapy. There was no difference between the owners and veterinary surgeons global assessments at baseline but there was at day 28 (P=0.02). The owners' scores decreased from a median of 5 at baseline to 3 at 28 days (P=0.0004) while the median veterinary surgeon scores decreased from 5 to 2 at 28 days (P<0.0001). There was a statistically significant reduction in the owners' scores for each of the four domains with the greatest reduction occurring in the activity category (P=0.0001). This study shows that owner assessment of changes in their cat's behaviour/lifestyle is an important method of identifying chronic pain in their pets.
2009 Oct 7;(4):CD007540.
Moore RA, Derry S, McQuay HJ.
Pain Research and Nuffield Department of Anaesthetics, University of Oxford, West Wing (Level 6), John Radcliffe Hospital, Oxford, Oxfordshire, UK, OX3 9DU.
Single dose oral sulindac for acute postoperative pain in adults.
BACKGROUND: Sulindac is a non-steroidal anti-inflammatory drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK, and widely available in other countries worldwide. This review sought to evaluate the efficacy and safety of oral sulindac in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties. OBJECTIVES: To assess the efficacy of single dose oral sulindac in acute postoperative pain, and any associated adverse events. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies up to June 2009. SELECTION CRITERIA: Randomised, double-blind, placebo-controlled clinical trials of oral sulindac for relief of acute postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We planned to use area under the "pain relief versus time" curve to derive the proportion of participants with meloxicam experiencing least 50% pain relief over 4 to 6 hours, using validated equations; to use number needed to treat to benefit (NNT); the proportion of participants using rescue analgesia over a specified time period; time to use of rescue analgesia; information on adverse events and withdrawals. MAIN RESULTS: No studies were identified by the searches that examined oral sulindac in patients with established postoperative pain. AUTHORS' CONCLUSIONS: In the absence of evidence of efficacy, at present, for oral sulindac in acute postoperative pain, its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes, there is no urgent research agenda.
2008 Dec;22(4):336-43.
Briscoe JA, Morris DO, Rankin SC, Hendrick MJ, Rosenthal KL.
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey Street, Philadelphia, PA 19104, USA.
Methicillin-resistant Staphylococcus aureus-associated dermatitis in a Congo African grey parrot (Psittacus erithacus erithacus).
A 2-year-old DNA-sexed female Congo African grey parrot (Psittacus erithacus erithacus) was evaluated for self-trauma of the feathers and skin of the tail base for a duration of more than 1 year. All rectrices and tail coverts were missing, the skin of the tail base was thickened and ulcerated, and the uropygial gland was swollen. Results of a complete blood cell count revealed relative monocytosis and basophilia. Survey radiographs showed truncation and lysis of the caudal vertebrae and pygostyle. Results of biopsy and bacterial culture of the tail base lesions revealed an ulcerative bacterial dermatitis positive for staphylococcal cassette chromosome mec (SCCmec) type IV (community-acquired) methicillin-resistant Staphylococcus aureus (MRSA). The bird was treated with oral trimethoprim-sulfamethoxazole, meloxicam, fluoxetine, topical lidocaine gel, and hydrotherapy. One month later, tail feather regrowth was evident; however, follow-up over 2 years found continued self-trauma to the rectrices in spite of repeated skin biopsies negative for MRSA or other bacteria. It is unknown if the MRSA cultured from this bird was commensal or acquired from either the environment or humans to which the bird was exposed.
2008 Dec 15;233(12):1883-8.
Olesen MG, Bertelsen MF, Perry SF, Wang T.
Department of Biological Sciences, University of Aarhus, Denmark.
Effects of preoperative administration of butorphanol or meloxicam on physiologic responses to surgery in ball pythons.
OBJECTIVE: To characterize physiologic responses of ball pythons (Python regius) following a minor surgical procedure and investigate the effects of 2 commonly used analgesics on this response. ANIMALS: 15 healthy ball pythons. PROCEDURES: Snakes were randomly assigned to receive 1 of 3 treatments: meloxicam (0.3 mg/kg [0.14 mg/lb]; n = 5), butorphanol (5 mg/kg [2.3 mg/lb]; 5), or saline (0.9% NaCl) solution (5) before catheterization of the vertebral artery. Plasma concentrations of catecholamines and cortisol, blood pressure, heart rate, and blood gas values were measured at various times for 72.5 hours after catheterization. The 72.5-hour point was defined as baseline. RESULTS: Heart rate of ball pythons increased significantly during the first hour following surgery. Mean plasma epinephrine concentration increased slightly at 2.5 hours after surgery, whereas mean plasma cortisol concentration increased beginning at 1.5 hours, reaching a maximum at 6.5 hours. Mean blood pressure increased within the first hour but returned to the baseline value at 2.5 hours after surgery. After 24.5 hours, blood pressure, heart rate, and plasma hormone concentrations remained stable at baseline values. There were no significant differences in values for physiologic variables between snakes that received saline solution and those that received meloxicam or butorphanol. CONCLUSIONS AND CLINICAL RELEVANCE: Measurement of physiologic variables provides a means of assessing postoperative pain in snakes. Meloxicam and butorphanol at the dosages used did not decrease the physiologic stress response and did not appear to provide analgesic effects in ball pythons.
2008 Oct;31(5):456-65.
Carroll GL, Narbe R, Peterson K, Kerwin SC, Taylor L, DeBoer M.
Department of Small Animal Clinical Sciences, Texas A&M University, College Station, TX 77843-4474, USA.
A pilot study: sodium urate synovitis as an acute model of inflammatory response using objective and subjective criteria to evaluate arthritic pain in cats.
Sodium urate (SU) synovitis was evaluated as a model for feline arthritic pain using a placebo- and positive-controlled (meloxicam) randomized blinded controlled single crossover design. Monosodium urate crystals [20 mg (1 mL) rod-shaped] were injected into alternate stifles of trained anesthetized cats (n = 3) with a 28 day washout. During the first trial phase, two cats received meloxicam (0.1 mg/kg, PO), a nonsteroidal anti-inflammatory drug (NSAID), for three days before and on the day of SU injection; the third cat received placebo. Treatments and stifles were switched for the second trial. Total force, contact pressure and area of the fore and hind limbs were measured using a pressure mat one day and 0.5 h before, and 2, 4, 6, 8, 10, 24, and 30 h post-SU injection. Skin temperature, joint circumference, analgesia, lameness, and visual analogue scale (VAS) pain scores, were measured at the same times. Comparisons were made for each time and for areas under the curve (AUC) using original and change from baseline; P < 0.05 was significant. Significant differences in force mat data and subjective data were found for the hind limb data (total force and total contact pressure at 6, 10, and 30 h; analgesia and VAS for pain at 4 h; lameness at 10, 24, and 30 h) and for AUC(0)-->(24h) and AUC(0)-->(30 h) (total force, total contact pressure, and mean lameness score) and for differences from BL AUC(0)-->(10h) (total contact area) and AUC(0)-->(24h) (total contact area and mean lameness score) and AUC(0)-->(30 h) (total force, total contact area, and mean lameness). No cats required rescue analgesia. Injection of 1 mL of monosodium urate into the stifle of a cat causes moderate transitory pain and was suitable for assessing analgesic efficacy of an NSAID with a pressure mat and subjective criteria.
2008 Jun;33(3):197-200.
Liu XD, Zhang JL, Zheng HG, Liu FY, Chen Y.
Department of Arthropathy, Zhejiang Provincial Hospital of Integrated Chinese and Western Medicine, Hangzhou 310003, China. liuxide2001@sohu.com
[Clinical randomized study of bee-sting therapy for rheumatoid arthritis] [Article in Chinese]
OBJECTIVE: To observe the clinical effect of bee-sting (venom) therapy in the treatment of rheumatoid arthritis (RA). METHODS: One hundred RA patients were randomly divided into medication (control) group and bee-venom group, with 50 cases in each. Patients of control group were treated with oral administration of Methotrexate (MTX, 7.5 mg/w), Sulfasalazine (0.5 g,t. i.d.), Meloxicam (Mobic,7. 5 mg, b. i. d.); and those of bee-venom group treated with Bee-sting of Ashi-points and the above-mentioned Western medicines. Ashi-points were selected according to the position of RA and used as the main acupoints, supplemented with other acupoints according to syndrome differentiation. The treatment was given once every other day and all the treatments lasted for 3 months. RESULTS: Compared with pre-treatment, scores of joint swelling degree, joint activity, pain, and pressing pain, joint-swelling number, grasp force, 15 m-walking duration, morning stiff duration in bee-venom group and medication group were improved significantly (P<0.05, 0.01). Comparison between two groups showed that after the therapy, scores of joint swelling, pain and pressing pain, joint-swelling number and morning stiff duration, and the doses of the administered MTX and Mobic in bee-venom group were all significantly lower than those in medication group (P<0.05, 0.01); whereas the grasp force in been-venom group was markedly higher than that in medication group (P<0.05). In addition, the relapse rate of bee-venom group was obviously lower than that of medication group (P<0.05; 12% vs 32%). CONCLUSION: Combined application of bee-venom therapy and medication is superior to simple use of medication in relieving RA, and when bee-sting therapy used, the commonly-taken doses of western medicines may be reduced, and the relapse rate gets lower.
2008 Aug;79(4):548-54.
van der Heide HJ, Hannink G, Buma P, Schreurs BW.
Department of Orthopedics, Orthopedic Research Laboratory, Nijmegen Medical Center, Radboud University, Nijmegen, the Netherlands.
No effect of ketoprofen and meloxicam on bone graft ingrowth: a bone chamber study in goats.
BACKGROUND AND PURPOSE: There is increasing awareness that non-steroidal anti-inflammatory drugs (NSAIDs), and especially the cyclooxygenase-2 (COX-2) selective ones, may retard bone healing. We have used NSAIDs (indomethacin for at least 7 days) to prevent heterotopic ossification after acetabular reconstructions using impacted bone grafts. The long-term clinical results have been satisfying, making it difficult to believe that there is an important negative effect of NSAIDs on graft incorporation. We studied the effect of two different NSAIDs on bone and tissue ingrowth in a bone chamber model in goats, using autograft, rinsed allograft, and allograft that had been rinsed and subsequently irradiated. METHODS: 9 goats received no NSAIDs, 9 received ketoprofen, and 9 received meloxicam--all for 6 weeks. In each goat 6 bone chambers were implanted: 2 filled with autograft, 2 with rinsed allograft, and 2 with allograft that had been rinsed and irradiated. The amount of bone ingrowth and total tissue ingrowth was compared between the groups. RESULTS: There were no statistically significant differences in bone ingrowth between the different groups. Also, no differences in bone ingrowth were found with respect to the type of graft used. Furthermore, there was no statistically significant difference in the total amount of ingrowth of fibrous tissue between the treatment groups. INTERPRETATION: No differences in bone ingrowth in titanium bone chambers could be detected with both ketoprofen and meloxicam compared to untreated control animals. This confirms our hypothesis that the effect of NSAIDs on the incorporation and ingrowth of bone graft is limited.
2007 Dec;37(12):798-805.
Pearson SA, Ringland C, Kelman C, Mant A, Lowinger J, Stark H, Nichol G, Day R, Henry D.
St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia. sallie.pearson@unsw.edu.au
Patterns of analgesic and anti-inflammatory medicine use by Australian veterans.
BACKGROUND: We examined analgesic and anti-inflammatory medicine use by Australian veterans before and after the introduction of selective Cox-2 inhibitors. METHODS: We studied cohorts of Gold Card-holding veterans using prescription data held by the Department of Veterans' Affairs for the period 1 July 1998 to 30 June 2004. Outcomes were volume dispensed, average daily quantity and cumulative incidence of use of paracetamol-containing and aspirin-containing medicines, non-selective and Cox-2-selective non-steroidal anti-inflammatory drugs (NSAIDs), tramadol and dextropropoxyphene. RESULTS: Overall, we found high levels of use of analgesic and anti-inflammatory medicines, which increased by 43% over the study period. Use of paracetamol-containing medicines was overtaken by NSAIDs in 1999/2000, corresponding to the introduction of the Cox-2-selective agents. Between 12 and 17% of Cox-2-selective medicine recipients were supplied amounts indicative of continuous use in relatively high doses and 51% of veterans received at least one relatively Cox-2-selective medicine (celecoxib, rofecoxib, meloxicam, diclofenac) by the end of the study period. Dextropropoxyphene use declined during the study and tramadol use increased 10-fold. CONCLUSION: This study shows very high levels of Cox-2 inhibitor use during the 6-year period. Cox-2-selective agents were more likely to be taken continuously and at higher doses than non-selective NSAIDs. This is relevant in view of the cardiovascular toxicity of this group of medicines. The study shows the value of using unit record dispensing data to assess drug use patterns. Linking dispensing records to hospital separation and mortality data will further enhance our ability to monitor drug safety.
2007 Sep-Oct;21(5):917-23.
Craven M, Chandler ML, Steiner JM, Farhadi A, Welsh E, Pratschke K, Shaw DJ, Williams DA.
Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK. mdc57@cornell.edu
Acute effects of carprofen and meloxicam on canine gastrointestinal permeability and mucosal absorptive capacity.
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed to dogs for their analgesic, antipyretic, and anti-inflammatory properties. Their beneficial actions can be offset by gastrointestinal (GI) toxicosis. Endoscopy has traditionally been employed to detect GI lesions, but alterations in GI permeability precede the development of mucosal damage. HYPOTHESIS: Carprofen and meloxicam alter GI permeability and mucosal absorptive capacity of dogs. ANIMALS: Twenty adult dogs treated with an NSAID for >7 days were evaluated by permeability tests while receiving either carprofen (10 dogs) or meloxicam (10 dogs). METHODS: Prospective, longitudinal observational study. A 6-sugar permeability test (sucrose, lactulose, rhamnose, 3-O-methyl-D-glucose, D-xylose, and sucralose) was performed on the day before NSAID treatment, and after 3 and 8 days of treatment. RESULTS: There were no significant differences in the urinary recovery ratios of lactulose: rhamnose, D-xylose: 3-O-methyl-D-glucose, or sucralose recovery within either group at any time during the study. Sucrose permeability in the meloxicam group did not alter significantly over time. However, sucrose permeability in the carprofen group decreased significantly by day 3 (P = .049) and increased again by day 8 (P = .049), to a level that was not significantly different to permeability before treatment (P = .695). CONCLUSIONS AND CLINICAL IMPORTANCE: The absence of increased GI permeability and diminished mucosal absorptive capacity in this group of dogs does not support the development of acute GI toxicosis during treatment with either meloxicam or carprofen.
2007 Aug;23(8):1859-66.
Sun SX, Lee KY, Bertram CT, Goldstein JL.
Walgreens Health Services, Deerfield, IL 60015, USA.
Withdrawal of COX-2 selective inhibitors rofecoxib and valdecoxib: impact on NSAID and gastroprotective drug prescribing and utilization.
OBJECTIVE: Cyclo-oxygenase-2 (COX-2) inhibitors rofecoxib and valdecoxib were withdrawn from the market because of their association with cardiovascular problems. There is a lack of information on the impact of the COX-2 inhibitors withdrawal on the prescribing and utilization of related drugs. The main objective of this study was to evaluate to what extent prescriptions of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and gastroprotective drugs changed after the removal of the two COX-2 inhibitors. RESEARCH DESIGN AND METHODS: A segmented regression of interrupted time series approach was used to analyze prescription data from July 1, 2003 through December 31, 2005 from a pharmacy claims database maintained by a large pharmacy benefit manager (PBM). Patients continuously eligible for the pharmacy benefit but not enrolled in COX-2 or proton pump inhibitor (PPI) Step Care programs during the study period were included. The number of prescriptions per thousand patients per month for targeted drugs were analyzed and compared. RESULTS: A total of 175 193 patients were included in the analysis. After the withdrawal of the COX-2 inhibitor, the average monthly non-selective NSAID and PPI prescriptions per thousand patients increased from 13.96 to 19.63 (a change of 40.62%, p < 0.0001) and from 38.67 to 43.33 (a change of 12.05%, p < 0.0001) respectively, whereas COX-2 prescriptions decreased by 54.51% (from 23.61 to 10.74, p < 0.0001). Among non-selective NSAIDs, the five drugs with highest percentage increase were meloxicam (167.12%, from 1.46 to 3.90, p < 0.0001), etodolac (72.06%, from 0.68 to 1.17, p < 0.0001), piroxicam (58.33%, from 0.36 to 0.57, p < 0.0001), nabumetone (52.38%, from 1.26 to 1.92, p < 0.0001), and diclofenac (37.89%, from 1.61 to 2.22, p < 0.0001). LIMITATIONS: This study was restricted to patients with employer-sponsored drug coverage which might not be representative of the national population. Since over-the-counter (OTC) PPI, non-selective NSAID and H2RA were not captured in our claims data, we were unable to examine whether and to what extent the utilization of these drugs has changed. Additionally, the direct impact of these changes on population based outcomes is unknown. CONCLUSIONS: After the withdrawal of COX-2 inhibitors rofecoxib and valdecoxib, there were significant increases in non-selective NSAID and PPI prescriptions but not H2RA and misoprostol. Given the safety concerns with the NSAIDs, further studies are warranted regarding the clinical outcomes associated with the increased use of non-selective NSAIDs with or without gastroprotective agents.
2007 May-Jun;21(3):410-6.
Lascelles BD, Hansen BD, Roe S, DePuy V, Thomson A, Pierce CC, Smith ES, Rowinski E.
Comparative Pain Research Laboratory, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA. Duncan_Lascelles@ncsu.edu
Evaluation of client-specific outcome measures and activity monitoring to measure pain relief in cats with osteoarthritis.
BACKGROUND: There are no validated systems for measuring pain from osteoarthritis in cats. HYPOTHESIS: Owner subjective assessments and an activity monitor (AM) can be used to detect pain in cats with osteoarthritis and to assess efficacy of treatments. ANIMALS: Thirteen cats older than 10 years old, with owner-assessed decreases in activity, painful arthritic joints, and clinically normal blood work were included and evaluated for 3 weeks. METHODS: A collar-mounted AM measured activity and a client-specific outcome measure (CSOM) questionnaire characterized the severity of impairment. Overall global quality of life was also evaluated for each treatment. In weeks 2 and 3, meloxicam (0.1 mg/kg, day 1; 0.05 mg/kg, days 2-5) or a placebo was administered in a blinded, randomized, cross-over manner to test the assessment systems. RESULTS: The cats had a median of 4 arthritic appendicular joints. Activity counts for the week when cats (complete data on activity; n=9) were administered meloxicam were significantly higher than at baseline (P = .02) but not after placebo (P = .06). Baseline activity counts were not significantly different from placebo (P = .6). The CSOM data (n=13) showed that owners considered their cats to be more active on meloxicam compared with baseline (P = .001) and placebo (P < .004), and more active on placebo than at baseline (P < .01). Global quality of life improved significantly with meloxicam (P < .042). CONCLUSIONS AND CLINICAL IMPORTANCE: Both an AM and a CSOM system can detect behavior associated with pain relief in cats that are arthritic. Objective activity data might allow subjective assessment systems to be validated for use in clinical studies.
2007 Jun;68(6):614-24.
Little D, Brown SA, Campbell NB, Moeser AJ, Davis JL, Blikslager AT.
Equine Health Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Effects of the cyclooxygenase inhibitor meloxicam on recovery of ischemia-injured equine jejunum.
OBJECTIVE: To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum. ANIMALS: 18 horses. PROCEDURES: Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial barrier function, histologic evaluation, and western blot analysis of ischemia-injured and control jejunal mucosa samples from the 3 groups were performed. RESULTS: Meloxicam- or flunixin-treated horses had improved postoperative pain scores and clinical variables, compared with SS-treated horses. Recovery of transepithelial barrier function in ischemia-injured jejunum was inhibited by flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue were higher in horses treated with meloxicam or flunixin than SS. Plasma meloxicam concentrations were similar to those reported previously, but clearance was slower. Changes in expression of proteins associated with inflammatory responses to ischemic injury and with different drug treatments occurred, suggesting cyclooxygenase-independent effects. CONCLUSIONS AND CLINICAL RELEVANCE: Although further assessment is needed, these data have suggested that IV administration of meloxicam may be a useful alternative to flunixin meglumine for postoperative treatment of horses with colic.
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.
A review to evaluate the degree of renal outcome of cyclo-oxygenase-2-selective inhibitors is pharmacokinetic dependent. Non-steroidal anti-inflammatory drugs may cause renal side effects.
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.
A study to evaluate the nonsteroidal anti-inflammatory drugs and hepatic toxicity. This systematic review was conducted in arthritis patients. Some times this nonsteroidal anti-inflammatory drugs may cause hepatic side effects.
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.
A review of pharmacokinetics, efficacy and safety of Meloxicam. It is a non-steroidal anti-inflammatory drug which belongs to oxicam class. This drug is usually used in the management of osteoarthritis and rheumatoid arthritis.
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]
A study to find out the effectiveness of movalis in treating patients with acute low back pain. Around 30 patients were participated in the study. The use of movalis in , injection and tablet forms were evaluated separately.
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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