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Marco Duz - One of the best experts on this subject based on the ideXlab platform.
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Proportion of nonsteroidal anti-inflammatory drug prescription in equine practice
'Wiley', 2018Co-Authors: Marco Duz, John Marshall, Tim ParkinAbstract:BACKGROUND: There is little knowledge of the prescription of nonsteroidal anti-inflammatory drugs (NSAIDs) and whether their prescription varies between countries. OBJECTIVE: To describe prescription practices of NSAIDs in equids in the United Kingdom (UK), United States of America (USA) and Canada. STUDY DESIGN: Descriptive observational study. METHODS: Free-text electronic medical records from 141,543 equids from 10 equine practices in the UK, 255,777 equids from 7 equine practices with 20 branches from the USA and 2 practices with 7 branches from Canada were evaluated. A validated text-mining technique was used to describe the proportion of equids prescribed NSAIDs at least once in these countries. The choice of NSAIDs in orthopaedic and colic cases was evaluated. RESULTS: The prescription of NSAIDs is more common in the USA (42.4%) and Canada (34.2%) than in the UK (28.6%). Phenylbutazone and flunixin meglumine were the drugs mostly prescribed in all countries. While flunixi meglumine was most prescribed with colic cases in all countries, a proportion received Phenylbutazone despite this drug being licensed for use only with musculoskeletal disease. Phenylbutazone was the most commonly prescribed drug in cases with orthopaedic disease followed by flunixin meglumine in all countries. Only a small proportion of cases received meloxicam, ketoprofen or firocoxib. MAIN LIMITATIONS: The retrospective design might have resulted in an unknown number of incomplete records, particularly in the reporting of colic and orthopaedic disease. Although the data set is large, the relatively small number of practices recruited from each country may introduce bias. CONCLUSIONS: Clinical practice can differ between countries although the influence of individual practitioners and practice-specific policy on apparent intercountry differences requires further research. Despite several other NSAIDs being available and a substantial effort being made to evaluate their efficacy, the prescription of NSAIDs other than Phenylbutazone and flunixin meglumine remains rather limited
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effect of Phenylbutazone flunixin meglumine and firocoxib on ex vivo cyclo oxygenase activity in horses undergoing elective surgery
Equine Veterinary Journal, 2013Co-Authors: Marco Duz, T D H Parkin, John F MarshallAbstract:Aims Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the production of prostaglandins and other inflammatory mediators by inhibiting the activity of the cyclo-oxygenase enzymes (COX). Two major isoforms of COX enzymes exist: COX-2, which is expressed during the inflammatory response, and COX-1, which is responsible for the physiological production of prostaglandin that regulates tissue homeostasis. The study aims to evaluate the effect of firocoxib ex vivo in the horse as, to the authors' knowledge, published studies assess its effect only in vitro. Methods Horses (n = 18) undergoing elective surgery were recruited and allocated to treatment groups depending on clinician preference (1) Phenylbutazone (4.4 mg/kg bwt i.v. b.i.d.), (2) flunixin meglumine (FM, 1.1 mg/kg bwt i.v. b.i.d.) and (3) firocoxib (FIR, 0.1 mg/kg bwt i.v. s.i.d.). Residual blood samples were collected prior to NSAIDs (T0), 2 h after NSAIDs (T2), and 24 h following surgery (T24). The COX activity was measured using validated immune-enzymatic assays. A Kruskall–Wallis test was used to determine the effect of time and treatment on COX-1 and COX-2 activity. Bonferroni corrections were used to identify the level of significance accounting for multiple comparisons (P<0.017). Results At T2 and T24, the relative COX-1 activity was significantly greater in horses receiving firocoxib compared with horses receiving either Phenylbutazone (P<0.008) or flunixin meglumine (P<0.005). At T2 and T24, COX-1 activity was reduced (compared with baseline) in horses receiving Phenylbutazone or flunixin meglumine. The effect on COX-2 activity was not significantly different between drugs (P = 0.471). Conclusions and practical significance Cyclo-oxygenase selectivity of firocoxib is demonstrated ex vivo. Firocoxib is as effective as Phenylbutazone or flunixin meglumine in modulating the production of prostaglandins by COX-2 isoenzyme, whilst the physiological action of COX-1 isoenzyme is preserved with firocoxib, but not with Phenylbutazone and flunixin ex vivo. Ethical animal research Study approved by Ethics and Welfare Committee - School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow. Sources of funding: Funding provided by John Crawford Endowment Fund, and Mrs I.J. Gates Charity Fund, University of Glasgow. Competing interests: None.
Heidi E. Banse - One of the best experts on this subject based on the ideXlab platform.
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impact of concurrent treatment with omeprazole on Phenylbutazone induced equine gastric ulcer syndrome egus
Equine Veterinary Journal, 2020Co-Authors: Megan Ricord, M. L. Keowen, Frank M. Andrews, Francisco J. Morales Yñiguez, F. Garza, Linda Paul, Ann Chapman, Heidi E. BanseAbstract:BACKGROUND Phenylbutazone is commonly prescribed for treatment of various painful or inflammatory disorders in horses, but is associated with gastrointestinal (GI) adverse effects. Anecdotally, many practitioners prescribe omeprazole concurrently with Phenylbutazone to reduce development of equine gastric ulcer syndrome (EGUS), but the efficacy and safety of this practice remains unknown. OBJECTIVES To evaluate the effect of omeprazole on Phenylbutazone-induced equine glandular gastric disease (EGGD) and equine squamous gastric disease (ESGD). STUDY DESIGN Randomised block experimental design. METHODS Twenty-two horses with EGGD and ESGD scores ≤2 were included. Horses were assigned to treatment groups: Phenylbutazone (4.4 mg/kg PO q 12 h; PBZ), Phenylbutazone plus omeprazole (4 mg/kg PO q. 24 h; PBZ/OME) or placebo (CON) in a randomised block design based upon initial EGGD score. Horses were treated for up to 14 days. Gastroscopy was performed weekly; CBC and biochemistry were performed at Day 0 and study end. Horses were monitored for signs of colic and/or diarrhoea. RESULTS EGGD score increased in PBZ (median change 1, inter-quartile range, [IQR], 0-2) compared to PBZ/OME (median change 0, IQR -1 to 0; P = .05). PBZ/OME (6/8) had more intestinal complications than CON (0/6; difference between proportions = 75%; 95% CI, 23%-93%; P = .03). Plasma protein concentrations decreased in PBZ, compared to CON (mean difference between groups, 14 g/L; 95% CI, 1.04-27; P = .03). Five horses were withdrawn from the study due to intestinal complications (n = 3 PBZ/OME and n = 2 PBZ); one horse (PBZ) was withdrawn due to severe grade 4 EGGD. MAIN LIMITATIONS Small sample size and changes in management for the 2-3 days prior to study initiation; variable treatment duration among groups due to development of complications. CONCLUSIONS Administration of omeprazole ameliorated PBZ-induced EGGD, but was associated with an increase in intestinal complications. Caution should be exercised when co-prescribing NSAIDs and omeprazole in horses, particularly in association with change in management.
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Phenylbutazone induces equine glandular gastric disease without decreasing prostaglandin e2 concentrations
Journal of Veterinary Pharmacology and Therapeutics, 2018Co-Authors: S K Pedersen, Alastair E Cribb, E K Read, D French, Heidi E. BanseAbstract:In equids, Phenylbutazone at high doses induces gastric disease, primarily in the glandular portion of the stomach. However, the mechanism of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric disease in horses has yet to be determined. While Phenylbutazone-associated ulceration is often attributed to a decrease in basal gastric prostaglandins, this has not been demonstrated in the horse. Twelve horses were randomly assigned to treatment (n = 6; 4.4 mg/kg Phenylbutazone PO in 20 ml molasses q 12 hr for 7 days) or placebo (n = 6; 20 ml molasses PO q 12 hr for 7 days) groups. Before treatment and 3 and 7 days after initiation of treatment, gastroscopy was performed and glandular gastric biopsies were collected and frozen at -80°C. Glandular disease was assessed on a scale of 0-4. Prostaglandin E2 concentrations in biopsies were measured using a commercially available enzyme-linked immunosorbent assay. All Phenylbutazone-treated horses developed grade ≥2 glandular disease. Prostaglandin concentrations increased over time (p = .0017), but there was no effect of treatment (p = .49). These findings indicate that despite induction of glandular disease grade ≥2, Phenylbutazone did not decrease basal glandular gastric prostaglandin E2 concentration.
M. L. Keowen - One of the best experts on this subject based on the ideXlab platform.
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impact of concurrent treatment with omeprazole on Phenylbutazone induced equine gastric ulcer syndrome egus
Equine Veterinary Journal, 2020Co-Authors: Megan Ricord, M. L. Keowen, Frank M. Andrews, Francisco J. Morales Yñiguez, F. Garza, Linda Paul, Ann Chapman, Heidi E. BanseAbstract:BACKGROUND Phenylbutazone is commonly prescribed for treatment of various painful or inflammatory disorders in horses, but is associated with gastrointestinal (GI) adverse effects. Anecdotally, many practitioners prescribe omeprazole concurrently with Phenylbutazone to reduce development of equine gastric ulcer syndrome (EGUS), but the efficacy and safety of this practice remains unknown. OBJECTIVES To evaluate the effect of omeprazole on Phenylbutazone-induced equine glandular gastric disease (EGGD) and equine squamous gastric disease (ESGD). STUDY DESIGN Randomised block experimental design. METHODS Twenty-two horses with EGGD and ESGD scores ≤2 were included. Horses were assigned to treatment groups: Phenylbutazone (4.4 mg/kg PO q 12 h; PBZ), Phenylbutazone plus omeprazole (4 mg/kg PO q. 24 h; PBZ/OME) or placebo (CON) in a randomised block design based upon initial EGGD score. Horses were treated for up to 14 days. Gastroscopy was performed weekly; CBC and biochemistry were performed at Day 0 and study end. Horses were monitored for signs of colic and/or diarrhoea. RESULTS EGGD score increased in PBZ (median change 1, inter-quartile range, [IQR], 0-2) compared to PBZ/OME (median change 0, IQR -1 to 0; P = .05). PBZ/OME (6/8) had more intestinal complications than CON (0/6; difference between proportions = 75%; 95% CI, 23%-93%; P = .03). Plasma protein concentrations decreased in PBZ, compared to CON (mean difference between groups, 14 g/L; 95% CI, 1.04-27; P = .03). Five horses were withdrawn from the study due to intestinal complications (n = 3 PBZ/OME and n = 2 PBZ); one horse (PBZ) was withdrawn due to severe grade 4 EGGD. MAIN LIMITATIONS Small sample size and changes in management for the 2-3 days prior to study initiation; variable treatment duration among groups due to development of complications. CONCLUSIONS Administration of omeprazole ameliorated PBZ-induced EGGD, but was associated with an increase in intestinal complications. Caution should be exercised when co-prescribing NSAIDs and omeprazole in horses, particularly in association with change in management.
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effects of pretreatment with ketoprofen and Phenylbutazone on experimentally induced synovitis in horses
American Journal of Veterinary Research, 1996Co-Authors: J G Owens, S R Stanton, M. L. Keowen, S G Kamerling, J S PrescottmathewsAbstract:Objective To compare the analgesic and anti-inflammatory effects of the nonsteroidal anti-inflammatory drugs (NSAID), ketoprofen (2.20 and 3.63 mg/kg of body weight) and Phenylbutazone (4.40 mg/kg), in an acute equine synovitis model. Design 4 groups of 6 horses received NSAID or saline solution in a randomized design. Animals 24 clinically normal mares and geldings. Procedure Left intercarpal joints were injected with sterile carrageenan to induce synovitis at the same time as IV administration of NSAID or saline solution. Clinical assessments were made and synovial fluid was withdrawn at 0, 1, 3, 6, 9, 12, 24, and 48 hours. Results The eicosanoids, prostaglandin E2 (PGE2) and leukotriene B4, increased in synovial fluid after synovitis induction in all horses then returned to near baseline by 48 hours. All NSAID-treated horses had decreased PGE2, compared with saline-treated horses. This effect lasted longer in Phenylbutazone-treated horses than in ketoprofen-treated horses. There were no treatment effects on leukotriene B4. In saline-treated animals, lameness, joint temperature, and synovial fluid volume, protein concentration, and nucleated cells increased 3 to 12 hours after induction, with marked reduction by 48 hours. Only Phenylbutazone treatment reduced lameness, joint temperature, and synovial fluid volume. Conclusion Phenylbutazone was more effective than ketoprofen in reducing lameness, joint temperature, synovial fluid volume, and synovial fluid PGE2. Results do not support lipoxygenase inhibition by either NSAID. Clinical relevance This reversible model induced synovial fluid alterations similar to those observed in horses with septic arthritis. Results indicate that Phenylbutazone may be more useful than ketoprofen in treating acute joint inflammation.
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Effects of ketoprofen and Phenylbutazone on chronic hoof pain and lameness in the horse.
Equine Veterinary Journal, 1995Co-Authors: J G Owens, S. S. Kamerling, S R Stanton, M. L. KeowenAbstract:The analgesic effects of the nonsteroidal anti-inflammatory drugs, ketoprofen (2.2 and 3.63 mg/kg bwt) and Phenylbutazone (4.4 mg/kg bwt) were compared in 7 horses with chronic laminitis. Hoof pain was quantified objectively by means of an electronic hoof tester and lameness was subjectively graded on a modified Obel scale. Ketoprofen at a dose of 3.63 mg/kg bwt (Phenylbutazone equimolar dose) reduced hoof pain and lameness to a greater extent than the 2.2 mg/kg dose and Phenylbutazone. These effects were still present at 24 h in 3 of the 4 pain tests, including lameness grade. These data suggest that ketoprofen at the dosage rate of 1.65 times the recommended therapeutic dose was more potent than Phenylbutazone in alleviating chronic pain and lameness in horses.
Francisco Moragues - One of the best experts on this subject based on the ideXlab platform.
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determination of Phenylbutazone and oxyphenbutazone in animal urine by ion trap liquid chromatography mass spectrometry
Analytica Chimica Acta, 2005Co-Authors: Carmen Igualada, Francisco MoraguesAbstract:Abstract The purpose of this study was to develop and validate a method to determine oxyphenbutazone and Phenylbutazone residues in urine of several animal species. Extraction from urine was performed using liquid extraction with chloroform after chemical hydrolysis. Final extract was analysed by reversed phase liquid chromatography–electrospray ionisation–mass spectrometry using an ion trap selective detector and Phenylbutazone-D10 as internal standard. The method was validated according to the requirements of the 2002/657/EC European decision and the calculated decision limit (CCα) and detection capability (CCβ) were 2 and 3 ng ml −1 , respectively.
Hweeling Koh - One of the best experts on this subject based on the ideXlab platform.
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analysis of adulterants in a traditional herbal medicinal product using liquid chromatography mass spectrometry mass spectrometry
Journal of Pharmaceutical and Biomedical Analysis, 2003Co-Authors: Aik Jiang Lau, Michael J Holmes, Sooon Woo, Hweeling KohAbstract:Abstract Adulterations with synthetic drugs are common problems with herbal medicine and this can potentially cause serious adverse effects. It is therefore important to determine the presence of synthetic drugs in herbal medicine to ensure patients’ safety. The objective of this study was to develop sensitive and specific methods to analyse Phenylbutazone, caffeine and oxyphenbutazone present in a traditional Indonesian herbal product. Liquid chromatography–mass spectrometry–mass spectrometry (LC–MS–MS) methods in the selected reaction-monitoring (SRM) mode were developed. It was found that the sample contained 0.53% w/w ( n =3, RSD=7.56%) Phenylbutazone and 0.04% w/w ( n =3, RSD=8.39%) caffeine. This corresponded to 43.17 mg Phenylbutazone and 3.23 mg caffeine in each sachet of powder. The methods were validated for linearity, precision, accuracy, LOD and LOQ. LOD and LOQ were found to be 3.69 and 12.29 ng/ml, respectively for Phenylbutazone. For caffeine, the LOD and LOQ were 0.84 and 2.80 ng/ml, respectively. Oxyphenbutazone in the sample was found to be present at a level below the quantification level of 10.2 ng/ml. With better methods developed for analysis of adulterants in herbal medicine, the quality and safety of these medicines can be better controlled and regulated to ensure patients’ safety.
