Dissolution rate enhancement of piroxicam by ordered mixing.

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Saharan, Vikas Anand; Choudhury, Pratim Kumar

2012-07-01

Micronized piroxicam was mixed with lactose, mannitol, sorbitol, maltitol and sodium chloride to produce ordered mixture in a glass vial by manual hand shaking method. The effect of excipients, surfactant, superdisintegrant, drug concentration and carrier particle size on dissolution rate was investigated. Dissolution rate studies of the prepared ordered mixtures revealed that all water soluble excipients increased the dissolution rate of piroxicam when compared to the dissolution rate of piroxicam or its suspension. Ordered mixture formulation PLF4, consisting of lactose as water soluble excipient, SSG (8% w/s) and SLS (1% w/w), released piroxcam at a very fast rate so much so that about 90% of the composition had passed into solution within 2 min. The order of the dissolution rate enhancement for ordered mixtures of various water soluble excipients was: lactose > mannitol > maltitol > sorbitol > sodium chloride. Carrier granules of size 355-710 µm were most effective in increasing the dissolution rate of drug from ordered mixtures. Decreasing the carrier particle size reduced drug dissolution from ordered mixtures. The dissolution rate of ordered mixtures consisting of 1-5% w/w piroxicam was superior to dissolution rate of piroxicam suspension. The dissolution data fitting and the resulting regression parameters indicated Hixson Crowell, cube root law, as the best fit to drug release data of ordered mixtures.

Ulcerogenicity of piroxicam: an analysis of spontaneously reported data.

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Rossi, A C; Hsu, J P; Faich, G A

1987-01-01

Previous reports have suggested that piroxicam may be more ulcerogenic than other non-steroidal anti-inflammatory drugs (NSAIDs) in use. Critics have attributed this putative relation to flawed comparisons of spontaneously reported data. In this study cases of upper gastrointestinal bleeding, perforation, and ulcer reported to the Food and Drug Administration's spontaneous reporting system over 12 years were examined. Reporting rates for eight NSAIDs were compared over identical periods of their marketing life cycles. After adjustments were made for the heterogeneity in the underlying reporting rates the difference in rates between piroxicam and the other drugs was considerably reduced but piroxicam retained its top ranking among the drugs; however, large and clinically important differences in the frequency of cases of upper gastrointestinal bleeding, perforation, and ulcer between piroxicam and the rest of the NSAIDs compared probably do not exist. PMID:3109543

The pharmacokinetics of piroxicam in elderly persons with and without renal impairment.

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Rudy, A C; Figueroa, N L; Hall, S D; Brater, D C

1994-01-01

1. Piroxicam pharmacokinetics were assessed in three groups of subjects: (1) young healthy volunteers, (2) healthy elderly subjects (mean +/- s.d. creatinine clearance 88 +/- 13 ml min-1), and (3) elderly patients with renal insufficiency (creatinine clearance 60 +/- 10 ml min-1) following the administration of piroxicam 20 mg as a single dose and after chronic dosing of 20 mg once daily for 4 weeks. 2. Piroxicam and 5'-hydroxypiroxicam concentrations were measured by h.p.l.c. in serum and urine samples collected for 96 h after the single dose and for 144 h after chronic dosing. Unbound concentrations of piroxicam were determined by ultrafiltration. 3. Elimination half-lives, steady state concentrations of piroxicam and 5'-hydroxypiroxicam, clearances of total and unbound piroxicam, volumes of distribution normalized for body weight, and urinary recovery of 5'-hydroxypiroxicam were not influenced by age or renal function. Volumes of distribution after the single dose were significantly lower in women compared with men (mean +/- s.d. 10.0 +/- 2.9 l vs 12.9 +/- 5.0 l; 95% confidence interval of the difference 0.1 to 5.6). 4. Percent unbound piroxicam values were 1.46 +/- 0.3% after the single dose and 1.45 +/- 0.2% at steady state. There were significant reductions in clearance and clearance of unbound piroxicam between single and chronic doses. The half-lives of 5'-hydroxypiroxicam (80.9 +/- 44 h) were significantly longer than those of piroxicam (54.9 +/- 26 h) after chronic dosing. PMID:8148211

A comparative study of flurbiprofen and piroxicam in osteoarthritis.

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Misra N

1992-10-01

Full Text Available In this single-blind, multiple-dose study the efficacy and tolerability of flurbiprofen was compared with that of piroxicam in 60 adult patients suffering from osteoarthritis of the knee. The patients were randomly allocated to receive either flurbiprofen 100 mg twice daily or piroxicam 20 mg once daily for a period of four weeks. Clinical assessments w.r.t. pain, tenderness, stiffness, swelling and general activity of patient were carried out prior to initiation of trial therapy and thereafter at weekly intervals for four weeks. The findings were graded. Though significant improvements as compared to baseline data occurred in both the treatment groups, flurbiprofen was found to be superior to piroxicam in improving pain on movement and at rest (p < 0.05. The incidence of side effects was less in the group receiving flurbiprofen (6% compared to 47% observed with piroxicam.

Solid-state dependent dissolution and oral bioavailability of piroxicam in rats.

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Lust, Andres; Laidmäe, Ivo; Palo, Mirja; Meos, Andres; Aaltonen, Jaakko; Veski, Peep; Heinämäki, Jyrki; Kogermann, Karin

2013-01-23

The aim of this study was to gain understanding about the effects of different solid-state forms of a poorly water-soluble piroxicam on drug dissolution and oral bioavailability in rats. Three different solid-state forms of piroxicam were studied: anhydrate I (AH), monohydrate (MH), and amorphous form in solid dispersion (SD). In addition, the effect of a new polymeric excipient Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) on oral bioavailability of piroxicam was investigated. Significant differences in the dissolution and oral bioavailability were found between the solid-state forms of piroxicam. Amorphous piroxicam in SD showed the fastest dissolution in vitro and a solid-state transformation to MH in the dissolution medium. Despite the presence of solid-state transformation, SD exhibited the highest rate and extent of oral absorption in rats. Oral bioavailability of other two solid-state forms decreased in the order AH and MH. The use of Soluplus® was found to enhance the dissolution and oral bioavailability of piroxicam in rats. The present study shows the importance of solid-state form selection for oral bioavailability of a poorly water-soluble drug. Copyright © 2012 Elsevier B.V. All rights reserved.

X-ray studies on piroxicam modifications

International Nuclear Information System (INIS)

Reck, G.; Bannier, G.; Hoehne, E.

1988-01-01

The anti-inflammatory drug piroxicam, 4-hydroxy-2-methyl-N-(2-pyridyl)2H-1,2-benzothiazine-3-car-boxamide-1,1-dioxide, crystallizes in three different forms, two anhydrates and one monohydrate. Crystal structure analyses of the monohydrate and one of the anhydrate were carried out by Bordner et al. and Kojic-Prodic et al., respectively. The results of the analysis of the third piroxicam modification and of an independently performed structure determination of the monohydrate are reported. Molecular structures and hydrogen bonding of all modifications are discussed. (author)

Biowaiver monographs for immediate release solid oral dosage forms: piroxicam.

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Shohin, Igor E; Kulinich, Julia I; Ramenskaya, Galina V; Abrahamsson, Bertil; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Groot, D W; Barends, Dirk M; Dressman, Jennifer B

2014-02-01

Literature and experimental data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing piroxicam in the free acid form are reviewed. Piroxicam solubility and permeability, its therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA), and corresponding dissolution data are taken into consideration. The available data suggest that according to the current biopharmaceutics classification system (BCS) and all current guidances, piroxicam would be assigned to BCS Class II. The extent of piroxicam absorption seems not to depend on manufacturing conditions or excipients, so the risk of bioinequivalence in terms of area under the curve (AUC) is very low, but the rate of absorption (i.e., BE in terms of Cmax ) can be affected by the formulation. Current in vitro dissolution methods may not always reflect differences in terms of Cmax for BCS Class II weak acids; however, minor differences in absorption rate of piroxicam would not subject the patient to unacceptable risks: as piroxicam products may be taken before or after meals, the rate of absorption cannot be considered crucial to drug action. Therefore, a biowaiver for IR piroxicam solid oral dosage form is considered feasible, provided that (a) the test product contains only excipients, which are also present in IR solid oral drug products containing piroxicam, which have been approved in ICH or associated countries, for instance, those presented in Table 3 of this paper; (b) both the test and comparator drug products dissolve 85% in 30 min or less at pH 1.2, 4.5, and 6.8; and (c) the test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. When not all of these conditions can be fulfilled, BE of the products should be established in vivo. © 2013 Wiley Periodicals, Inc. and the

Solid state transformations in consequence of electrospraying--a novel polymorphic form of piroxicam.

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Nyström, Maija; Roine, Jorma; Murtomaa, Matti; Mohan Sankaran, R; Santos, Hélder A; Salonen, Jarno

2015-01-01

The aim of the research was to verify that electrospraying of piroxicam yielded a new polymorphic form of this drug. In the experiments, piroxicam was dissolved in chloroform and the solution was atomised electrostatically. Subsequently, the charged droplets were neutralised and dried. The solid drug particles were collected and analysed by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, high performance liquid chromatography, and infrared and Raman spectroscopy. The X-ray diffractogram measured for the electrosprayed piroxicam particles did not match with any of the known piroxicam crystal structures (Cambridge Crystallographic Data Centre). The variable temperature X-ray diffraction showed that the structure recrystallised completely into piroxicam polymorphic formI during heating. No degradation products or solvate removal was detected by high performance liquid chromatography and thermal analysis. The infrared and Raman spectra of the electrosprayed piroxicam were compared to those of formI, and some notable differences in the peak positions, shapes and intensities were detected. The results indicate that electrospraying leads to piroxicam crystallisation in a currently unknown polymorphic form. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of aceclofenac with piroxicam in the treatment of osteoarthritis.

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Peréz Busquier, M; Calero, E; Rodríguez, M; Castellon Arce, P; Bermudez, A; Linares, L F; Mesa, J; Ffernandez Crisostomos, C; Garcia, C; Garcia Lopez, A; Valenzuela, A; Povedano, A; Garcia Perez, S; Lopez, M A; Caliz, R; Garcia Villalba, F; Cano, M; Gines Martinez, F; Gonzalez, J; Caracuel, M A; Roldan, R; Guzman Ubeda, M; Gonzalez, A; Marenco de la Fuente, I L; Alepuz Pou, M

1997-03-01

A multicentre, double-blind, randomised, parallel group study was undertaken to investigate the efficacy and safety of aceclofenac (123 patients, 100 mg twice daily) in comparison to piroxicam (117 patients, 20 mg once daily and placebo once daily) in patients with osteoarthritis of the knee. The treatment period of two months was preceded by a washout period of one week duration. On completion of the study, patients in both aceclofenac and piroxicam-treated groups exhibited significant improvement in pain intensity and functional capacity of the affected knee, as represented by the Osteoarthritis Severity Index (OSI) (p < 0.0001 and p < 0.001 respectively). This was further substantiated following the patient's assessment of pain intensity using the Visual Analogue Scale (VAS), in which significant improvements were demonstrated at all time points for each treatment group (p < 0.001). Although both treatment groups showed a significant improvement in all investigator's clinical assessments (functional exploration of the knee, knee flexion and extension (EXT)), there were no significant differences between the groups. There was, however, a more rapid improvement in knee flexion in the aceclofenac group after 15 days of treatment. Both aceclofenac and piroxicam were well tolerated by patients, the most commonly reported adverse events being gastrointestinal, although their incidence was low. Only 24 patients on aceclofenac, as opposed to 33 on piroxicam complained of dyspepsia, epigastralgia and pyrosis. While 7 patients in each group were withdrawn because of adverse events, only one patient with piroxicam was withdrawn because of severe upper gastrointestinal bleeding. Twice as many reports of fecal blood loss were made in the piroxicam group in comparison to the aceclofenac group. In summary, this study confirms the therapeutic efficacy of aceclofenac and suggests that it is a well-tolerated alternative NSAID to piroxicam in the treatment of osteoarthritis.

Enhanced Dissolution and Oral Bioavailability of Piroxicam Formulations: Modulating Effect of Phospholipids

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Muhammad D. Hussain

2010-10-01

Full Text Available Several biologically relevant phospholipids were assessed as potential carriers/additives for rapidly dissolving solid formulations of piroxicam (Biopharmaceutics Classification System Class II drug. On the basis of in vitro dissolution studies, dimyristoylphosphatidylglycerol (DMPG was ranked as the first potent dissolution rate enhancer for the model drug. Subsequently, the solid dispersions of varying piroxicam/DMPG ratios were prepared and further investigated. Within the concentration range studied (6.4-16.7 wt %, the dissolution rate of piroxicam from the solid dispersions appeared to increase as a function of the carrier weight fraction, whereas the cumulative drug concentration was not significantly affected by piroxicam/DMPG ratio, presumably due to a unique phase behavior of the aqueous dispersions of this carrier phospholipid. Solid state analysis of DMPG-based formulations reveled that they are two-component systems, with a less thermodynamically stable form of piroxicam (Form II being dispersed within the carrier. Finally, oral bioavailability of piroxicam from the DMPG-based formulations in rats was found to be superior to that of the control, as indicated by the bioavailability parameters, cmax and especially Tmax (53 µg/mL within 2 h vs. 39 µg/mL within 5.5 h, respectively. Hence, DMPG was regarded as the most promising carrier phospholipid for enhancing oral bioavailability of piroxicam and potentially other Class II drugs.

Effect of piroxicam on lipid membranes: Drug encapsulation and gastric toxicity aspects.

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Wilkosz, Natalia; Rissanen, Sami; Cyza, Małgorzata; Szybka, Renata; Nowakowska, Maria; Bunker, Alex; Róg, Tomasz; Kepczynski, Mariusz

2017-03-30

Uptake of piroxicam, a non-steroidal anti-inflammatory drug, from the intestines after oral intake is limited due to its low solubility and its wide use is associated with several side effects related to the gastrointestinal tract. In this study, all-atom molecular dynamics (MD) simulations and fluorescent spectroscopy were employed to investigate the interaction of piroxicam in neutral, zwitterionic, and cationic forms with lipid bilayers composed of phosphatidylcholine, cholesterol, and PEGylated lipids. Our study was aimed to assess the potential for encapsulation of piroxicam in liposomal carriers and to shed more light on the process of gastrointestinal tract injury by the drug. Through both the MD simulations and laser scanning confocal microscopy, we have demonstrated that all forms of piroxicam can associate with the lipid bilayers and locate close to the water-membrane interface. Conventional liposomes used in drug delivery are usually stabilized by the addition of cholesterol and have their bloodstream lifetime extended through the inclusion of PEGylated lipids in the formulation to create a protective polymer corona. For this reason, we tested the effect of these two modifications on the behavior of piroxicam in the membrane. When the bilayer was PEGylated, piroxicam localize to the PEG layer and within the lipid headgroup region. This suggests that PEGylated liposomes are capable of carrying a larger quantity of piroxicam than the conventional ones. Copyright © 2017 Elsevier B.V. All rights reserved.

Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement

International Nuclear Information System (INIS)

Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant

2013-01-01

Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide-co-glycolide) (PLGA) microparticles (size 1–4 μm, encapsulation efficiency 80–85 %) and nanoparticles (size 151.6 ± 28.6 nm, encapsulation efficiency 92.17 ± 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.

Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement

Energy Technology Data Exchange (ETDEWEB)

Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant, E-mail: pmishra@dbeb.iitd.ac.in [Indian Institute of Technology Delhi, Department of Biochemical Engineering and Biotechnology (India)

2013-03-15

Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide-co-glycolide) (PLGA) microparticles (size 1-4 {mu}m, encapsulation efficiency 80-85 %) and nanoparticles (size 151.6 {+-} 28.6 nm, encapsulation efficiency 92.17 {+-} 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.

Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement

Science.gov (United States)

Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant

2013-03-01

Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide- co-glycolide) (PLGA) microparticles (size 1-4 μm, encapsulation efficiency 80-85 %) and nanoparticles (size 151.6 ± 28.6 nm, encapsulation efficiency 92.17 ± 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.

Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages.

Science.gov (United States)

Chiong, Hoe Siong; Yong, Yoke Keong; Ahmad, Zuraini; Sulaiman, Mohd Roslan; Zakaria, Zainul Amiruddin; Yuen, Kah Hay; Hakim, Muhammad Nazrul

2013-01-01

Liposomal drug delivery systems, a promising lipid-based nanoparticle technology, have been known to play significant roles in improving the safety and efficacy of an encapsulated drug. Liposomes, prepared using an optimized proliposome method, were used in the present work to encapsulate piroxicam, a widely prescribed nonsteroidal anti-inflammatory drug. The cytotoxic effects as well as the in vitro efficacy in regulation of inflammatory responses by free-form piroxicam and liposome-encapsulated piroxicam were evaluated using a lipopolysaccharide-sensitive macrophage cell line, RAW 264.7. Cells treated with liposome-encapsulated piroxicam demonstrated higher cell viabilities than those treated with free-form piroxicam. In addition, the liposomal piroxicam formulation resulted in statistically stronger inhibition of pro-inflammatory mediators (ie, nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2) than piroxicam at an equivalent dose. The liposome-encapsulated piroxicam also caused statistically significant production of interleukin-10, an anti-inflammatory cytokine. This study affirms the potential of a liposomal piroxicam formulation in reducing cytotoxicity and enhancing anti-inflammatory responses in vitro.

Piroxicam and laser phototherapy in the treatment of TMJ arthralgia: a double-blind randomised controlled trial.

Science.gov (United States)

de Carli, M L; Guerra, M B; Nunes, T B; di Matteo, R C; de Luca, C E P; Aranha, A C C; Bolzan, M C; Witzel, A L

2013-03-01

This study aimed to evaluate the efficacy of piroxicam associated with low-level laser therapy compared with single therapies in 32 patients presenting temporomandibular joint arthralgia in a random and double-blind research design. The sample, divided into laser + piroxicam, laser + placebo piroxicam and placebo laser + piroxicam groups, was submitted to the treatment with infrared laser (830 nm, 100 mW, 28 s, 100 J cm(-2) ) at 10 temporomandibular joint and muscle points on each side during four sessions concomitant to take one capsule a day of piroxicam 20 mg during 10 days. The treatment was evaluated throughout four sessions and 30 days follow-up through visual analogue scale (VAS), maximum mouth opening and joint and muscle (temporal and masseter) pain on palpation. The results showed that all the study groups had a significant improvement in the VAS scores (P Piroxicam was effective in the reduction of joint and muscle pain on palpation (P piroxicam was not more effective than single therapies in the treatment of temporomandibular joint arthralgia. The use of piroxicam was more effective in the following 30 days. © 2012 Blackwell Publishing Ltd.

In vitro and In vivo Characterisation of Piroxicam-Loaded Dika Wax ...

African Journals Online (AJOL)

Purpose: To formulate piroxicam-loaded lipospheres and evaluate their in vitro and in vivo properties. Method: Piroxicam-loaded lipospheres were prepared by hot homogenization technique using dika wax and Phospholipon® 90G (1:1, 1:2 and 2:1) as the lipid matrix. Characterisation, based on particle size

Radiochemical and biological characteristics of 99mTc-piroxicam for scintigraphy of inflammatory lesions

International Nuclear Information System (INIS)

El-Ghany, E.A.; Amine, A.M.; El-Kolaly, M.T.; El-Sayed, A.S.; Abdel-Gelil, F.

2005-01-01

Piroxicam was labeled effectively with 99m Tc due to the presence of electron donating atoms such as sulfur, nitrogen, and oxygen in its structure. The labeling yield was found to be influenced by different factors such as the amount of piroxicam, stannous chloride dihydrate, pH of the reaction mixture, reaction time and reaction temperature. The suitable amount of stannous chloride dihydrate required to produce high labeling yield of 99m Tc-piroxicam was 50 μg, above this quantity (200 μg) a colloidal solution was formed. Another factor which plays a significant role in this labeling reaction is the pH of the reaction medium. The labeling reaction was done only at alkaline pH range from 9-11, because piroxicam was not soluble at acidic or neutral pH. The labeling reaction proceeded well at room temperature and the complex was decomposed by heat. The labeled piroxicam ( 99m Tc-piroxicam ) showed good localization in inflamed foci and good imaging must be taken at 24-hour post injection, as the ratio of both types of inflammation (sterile and septic) to the background are 10.6 and 8.7, respectively. (author)

Piroxicam and Doxepin—An Alternative to Narcotic Analgesics in Managing Advanced Cancer Pain

Science.gov (United States)

Cohn, L.; Machado, Antonio F.; Bier, Robert; Cohn, Marthe

1988-01-01

To provide an effective continuum of the relief of severe carcinomatous pain with minimal side reactions, we initiated treatment with piroxicam (60 to 120 mg per day) and doxepin hydrochloride (25 to 225 mg per day). Of 30 patients presenting with severe pain of cancer of various origins, 7 continued to death with piroxicam and doxepin therapy. An additional 17 were successfully treated for 6 to 66 weeks with therapy reported here but, as disease progressed, required supplemental narcotics. The remaining six abandoned the use of piroxicam due to complications of therapy, which ranged from diarrhea to gastric perforation; serious complications were associated with patients' failure to adhere to a prescribed regimen of sucralfate. Therapy with piroxicam and doxepin proved to be safe and efficacious. PMID:3363962

Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages

Directory of Open Access Journals (Sweden)

Chiong HS

2013-03-01

Full Text Available Hoe Siong Chiong,1 Yoke Keong Yong,1 Zuraini Ahmad,1 Mohd Roslan Sulaiman,1 Zainul Amiruddin Zakaria,1 Kah Hay Yuen,2 Muhammad Nazrul Hakim1,31Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 2School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, Malaysia; 3Sports Academy, Universiti Putra Malaysia, Serdang, MalaysiaBackground: Liposomal drug delivery systems, a promising lipid-based nanoparticle technology, have been known to play significant roles in improving the safety and efficacy of an encapsulated drug.Methods: Liposomes, prepared using an optimized proliposome method, were used in the present work to encapsulate piroxicam, a widely prescribed nonsteroidal anti-inflammatory drug. The cytotoxic effects as well as the in vitro efficacy in regulation of inflammatory responses by free-form piroxicam and liposome-encapsulated piroxicam were evaluated using a lipopolysaccharide-sensitive macrophage cell line, RAW 264.7.Results: Cells treated with liposome-encapsulated piroxicam demonstrated higher cell viabilities than those treated with free-form piroxicam. In addition, the liposomal piroxicam formulation resulted in statistically stronger inhibition of pro-inflammatory mediators (ie, nitric oxide, tumor necrosis factor-α, interleukin-1β, and prostaglandin E2 than piroxicam at an equivalent dose. The liposome-encapsulated piroxicam also caused statistically significant production of interleukin-10, an anti-inflammatory cytokine.Conclusion: This study affirms the potential of a liposomal piroxicam formulation in reducing cytotoxicity and enhancing anti-inflammatory responses in vitro.Keywords: liposomes, nitric oxide, cytokines, prostaglandin E2, interleukin-1β, piroxicam

Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma.

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Alfonso Baldi

Full Text Available BACKGROUND: Malignant mesothelioma (MM is a rare, highly aggressive tumor, associated to asbestos exposure. To date no chemotherapy regimen for MM has proven to be definitively curative, and new therapies for MM treatment need to be developed. We have previously shown in vivo that piroxicam/cisplatin combined treatment in MM, specifically acts on cell cycle regulation triggering apoptosis, with survival increase. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed, at molecular level, the apoptotic increase caused by piroxicam/cisplatin treatment in MM cell lines. By means of genome wide analyses, we analyzed transcriptional gene deregulation both after the single piroxicam or cisplatin and the combined treatment. Here we show that apoptotic increase following combined treatment is mediated by p21, since apoptotic increase in piroxicam/cisplatin combined treatment is abolished upon p21 silencing. CONCLUSIONS/SIGNIFICANCE: Piroxicam/cisplatin combined treatment determines an apoptosis increase in MM cells, which is dependent on the p21 expression. The results provided suggest that piroxicam/cisplatin combination might be tested in clinical settings in tumor specimens that express p21.

Apoptosis Induced by Piroxicam plus Cisplatin Combined Treatment Is Triggered by p21 in Mesothelioma

Science.gov (United States)

Baldi, Alfonso; Piccolo, Maria Teresa; Boccellino, Maria Rosaria; Donizetti, Aldo; Cardillo, Irene; La Porta, Raffaele; Quagliuolo, Lucio; Spugnini, Enrico P.; Cordero, Francesca; Citro, Gennaro; Menegozzo, Massimo; Calogero, Raffaele A.; Crispi, Stefania

2011-01-01

Background Malignant mesothelioma (MM) is a rare, highly aggressive tumor, associated to asbestos exposure. To date no chemotherapy regimen for MM has proven to be definitively curative, and new therapies for MM treatment need to be developed. We have previously shown in vivo that piroxicam/cisplatin combined treatment in MM, specifically acts on cell cycle regulation triggering apoptosis, with survival increase. Methodology/Principal Findings We analyzed, at molecular level, the apoptotic increase caused by piroxicam/cisplatin treatment in MM cell lines. By means of genome wide analyses, we analyzed transcriptional gene deregulation both after the single piroxicam or cisplatin and the combined treatment. Here we show that apoptotic increase following combined treatment is mediated by p21, since apoptotic increase in piroxicam/cisplatin combined treatment is abolished upon p21 silencing. Conclusions/Significance Piroxicam/cisplatin combined treatment determines an apoptosis increase in MM cells, which is dependent on the p21 expression. The results provided suggest that piroxicam/cisplatin combination might be tested in clinical settings in tumor specimens that express p21. PMID:21858171

FT-Raman and FT-IR studies of 1:2.5 piroxicam: β-cyclodextrin inclusion compound

Science.gov (United States)

Bertoluzza, A.; Rossi, M.; Taddei, P.; Redenti, E.; Zanol, M.; Ventura, P.

1999-05-01

The FT-Raman and FT-IR spectra of amorphous 1:2.5 piroxicam (P): β-cyclodextrin (βCD) inclusion compound (PβCD) are presented and discussed in comparison with the spectra of the three main modifications of piroxicam (α,β and monohydrate). In the 1700-1200 cm -1 FT-Raman spectrum of 1:2.5 PβCD inclusion compound the bands of βCD are weak and covered by those stronger of piroxicam, differently from the FT-IR spectrum where the bands of βCD are stronger, so covering a large part of the spectrum. Typical FT-Raman marker bands are assigned for the characterization of the three modifications of piroxicam. The FT-Raman spectrum of 1:2.5 PβCD inclusion compound predominantly shows the bands at about 1465 and 1400 cm -1 of the monohydrate, indicating that piroxicam assumes the zwitterionic structure stabilized by interaction with βCD via electrostatic and hydrogen bonds. The dipolar character of 1:2.5 PβCD inclusion compound improves the solubility and the dissolution rate of piroxicam and thus its rate of absorption.

Derivatization of enolic OH of piroxicam: a comparative study on esters and sulfonates

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Jayaselli, J.; Cheemala, J. Manila Sagar; Geetha Rani, D.P.; Pal, Sarbani [MNR Post Graduate College, Kukatpally, Hyderabad (India). Dept. of Chemistry]. E-mail: sarbani277@yahoo.com

2008-07-01

A number of ester and sulfonate derivatives of piroxicam were prepared via acylation/sulfonation of the enolic OH of piroxicam. All the compounds were evaluated for their chemical stability and cyclooxygenase inhibiting properties. Data suggested that esters could be useful for the development of potential prodrugs. The sulfonate derivatives prepared for the first time were found to be stable. One of them showed a moderately selective COX-2 inhibition over COX-1 and would have lower gastrointestinal side effects than piroxicam due to the masked enolic OH group. A plausible mechanism for the acylation/sulfonation process has been proposed that involves participation of the pyridine moiety of piroxicam. Molecular structure of one of the ester was established for the first time by the crystal structure analysis from X-ray powder data. (author)

Derivatization of enolic OH of piroxicam: a comparative study on esters and sulfonates

International Nuclear Information System (INIS)

Jayaselli, J.; Cheemala, J. Manila Sagar; Geetha Rani, D.P.; Pal, Sarbani

2008-01-01

A number of ester and sulfonate derivatives of piroxicam were prepared via acylation/sulfonation of the enolic OH of piroxicam. All the compounds were evaluated for their chemical stability and cyclooxygenase inhibiting properties. Data suggested that esters could be useful for the development of potential prodrugs. The sulfonate derivatives prepared for the first time were found to be stable. One of them showed a moderately selective COX-2 inhibition over COX-1 and would have lower gastrointestinal side effects than piroxicam due to the masked enolic OH group. A plausible mechanism for the acylation/sulfonation process has been proposed that involves participation of the pyridine moiety of piroxicam. Molecular structure of one of the ester was established for the first time by the crystal structure analysis from X-ray powder data. (author)

Piroxicam-mediated modulatory action of 5-hydroxytryptamine serves as a "brake" on neuronal excitability in ischemic stroke

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Pallab Bhattacharya

2015-01-01

Full Text Available Our previous studies indicated an increase in extracellular γ-aminobutyric acid (GABA in rodent′s ischemic brain after Piroxicam administration, leading to alleviation of glutamate mediated excitotoxicity through activation of type A GABA receptor (GABAA. This study was to investigate if GABAA activation by Piroxicam affects extracellular 5-hydroxytryptamine or not. High performance liquid chromatography revealed that there was a significant decrease in extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum in Piroxicam pre-treated rat brains. This suggests a probable role of Piroxicam in reducing extracellular 5-hydroxytryptamine release in ischemic cerebral cortex and striatum possibly due to the GABAA activation by Piroxicam.

Effective method for the detection of piroxicam in human plasma using HPLC

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Adriana Maria CALVO

2016-01-01

Full Text Available Abstract Non-steroidal anti-inflammatory drugs (NSAIDs are widely used by the general population to alleviate inflammation and pain after oral surgeries. Piroxicam is among the most commonly used NSAIDs and excels in controlling pain, swelling, trismus and other common symptoms of inflammation. This study aimed to evaluate different concentrations of piroxicam and its major metabolite, 5’-hydroxypiroxicam, in human plasma samples over time using high performance liquid chromatography (HPLC after liquid-liquid extraction. Briefly, 10 volunteers participated in this study after approval by the Ethics Committee of Bauru School of Dentistry, Universidade de São Paulo – USP, Brazil. Volunteers received a single dose oral of piroxicam (20 mg and had blood collected at various times following an established protocol. The methodology of liquid-liquid extraction was effective for determining concentrations of piroxicam in plasma using HPLC in 10 out of 10 volunteers while 5’-hydroxypiroxicam was only detected in 2 out of 10 volunteers.

Effective method for the detection of piroxicam in human plasma using HPLC.

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Calvo, Adriana Maria; Prado, Mariel Tavares de Oliveira; Dionísio, Thiago José; Marques, Maria Paula; Brozoski, Daniel Thomas; Lanchote, Vera Lúcia; Faria, Flávio Augusto Cardoso; Santos, Carlos Ferreira

2016-05-20

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used by the general population to alleviate inflammation and pain after oral surgeries. Piroxicam is among the most commonly used NSAIDs and excels in controlling pain, swelling, trismus and other common symptoms of inflammation. This study aimed to evaluate different concentrations of piroxicam and its major metabolite, 5'-hydroxypiroxicam, in human plasma samples over time using high performance liquid chromatography (HPLC) after liquid-liquid extraction. Briefly, 10 volunteers participated in this study after approval by the Ethics Committee of Bauru School of Dentistry, Universidade de São Paulo - USP, Brazil. Volunteers received a single dose oral of piroxicam (20 mg) and had blood collected at various times following an established protocol. The methodology of liquid-liquid extraction was effective for determining concentrations of piroxicam in plasma using HPLC in 10 out of 10 volunteers while 5'-hydroxypiroxicam was only detected in 2 out of 10 volunteers.

Effectiveness of piroxicam and ibuprofen premedication on orthodontic patients' pain experiences.

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Kohli, Sarvraj Singh; Kohli, Virinder Singh

2011-11-01

To compare the effectiveness of preoperative administration of ibuprofen and piroxicam on orthodontic pain experienced after separator placement. Ninety patients aged between 13 years 9 months and 18 years 2 months who were to undergo fixed appliance orthodontic treatment were enrolled in this double-blind, parallel-arm, prospective study. Patients were evenly and randomly distributed to any of three experimental groups, as follows: (1) administration of placebo, (2) administration of 400 mg ibuprofen, and (3) administration of 20 mg piroxicam; medications were administered 1 hour before separator placement. The pain perceived was recorded by the patients on a linear and graded Visual Analogue Scale at time intervals of 2 hours; 6 hours; nighttime on the day of appointment; 24 hours after the appointment; and 2 days, 3 days, and 7 days after separator placement during each of the four activities (viz, chewing, biting, fitting front teeth, and fitting back teeth). The results revealed that preoperative administration of 20 mg of piroxicam 1 hour prior to separator placement resulted in a significant decrease in pain levels at 2 hours, 6 hours, nighttime, and 24 hours and on the second and third days after separator placement, compared to patients on a placebo or ibuprofen. Premedication with 20 mg of piroxicam results in significantly decreased pain experienced, compared to premedication with 400 mg of ibuprofen or placebo. Usage of 20 mg of piroxicam 1 hour prior to separator placement is recommended.

Piroxicam loaded alginate beads obtained by prilling/microwave tandem technique: morphology and drug release.

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Aquino, Rita P; Auriemma, Giulia; d'Amore, Matteo; D'Ursi, Anna Maria; Mencherini, Teresa; Del Gaudio, Pasquale

2012-07-01

This paper presents a tandem technique, based on the combination of prilling and microwave (MW) assisted treatments, to produce biodegradable alginate carriers of piroxicam with different drug controlled release behaviours. Results showed that alginate/piroxicam beads demonstrated high encapsulation efficiency and very narrow dimensional distribution. Beads dried by MW retained shape and size distribution of the hydrated particles while drying rate was strongly increased compared to convective drying processes. Moreover, different MW irradiation regimes promoted interactions between the drug and alginate matrix, affected drug polymorphism as well as inner and surface matrix structure leading to different piroxicam release profiles. High level MW irradiation led to beads with highly porous and swellable matrix able to release piroxicam in few minutes in the intestine while convective drying produced gastro-resistant beads that exhibit sustained piroxicam release (total release in 5.5h) in intestinal environment. On these results the tandem technique prilling/MW irradiation appears to be promising to obtain alginate carrier with tailored NSAIDs release depending on drug characteristics and MW irradiation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Study of surface activity of piroxicam at the interface of palm oil esters and various aqueous phases.

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Abdulkarim, Muthanna Fawzy; Abdullah, Ghassan Zuhair; Chitneni, Mallikarjun; Yam, Mun Fei; Mahdi, Elrashid Saleh; Salman, Ibrahim Muhammad; Ameer, Omar Ziad; Sattar, Munavvar Abdul; Basri, Mahiran; Noor, Azmin Mohd

2012-04-01

The surface activity of some non-steroidal anti-inflammatory agents like ibuprofen was investigated extensively. This fact has attracted the researchers to extend this behavior to other agents like piroxicam. Piroxicam molecules are expected to orient at the interface of oil and aqueous phase. The aim of this study was, firstly, to assess the surface and interfacial tension behaviour of newly synthesised palm oil esters and various pH phosphate buffers. Furthermore, the surface and interfacial tension activity of piroxicam was studied. All the measurements of surface and interfacial tension were made using the tensiometer. The study revealed that piroxicam has no effect on surface tension values of all pH phosphate buffers and palm oil esters. Similarly, various concentrations of piroxicam did not affect the interfacial tensions between the oil phase and the buffer phases. Accordingly, the interfacial tension values of all mixtures of oil and phosphate buffers were considerably high which indicates the immiscibility. It could be concluded that piroxicam has no surface activity. Additionally, there is no surface pressure activity of piroxicam at the interface of plam oil esters and phosphate buffers in the presence of Tweens and Spans.

UV-vis Imaging of Piroxicam Supersaturation, Precipitation, and Dissolution in a Flow-Through Setup.

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Sun, Yu; Chapman, Alex; Larsen, Susan W; Jensen, Henrik; Petersen, Nickolaj J; Goodall, David M; Østergaard, Jesper

2018-06-05

Evaluation of drug precipitation is important in order to address challenges regarding low and variable bioavailability of poorly water-soluble drugs, to assess potential risk of patient safety with infusion therapy, and to explore injectable in situ suspension-forming drug delivery systems. Generally, drug precipitation is assessed in vitro through solution concentration analysis methods. Dual-wavelength UV-vis imaging is a novel imaging technique that may provide an opportunity for simultaneously monitoring changes in both solution and solid phases during precipitation. In the present study, a multimodal approach integrating UV-vis imaging, light microscopy, and Raman spectroscopy was developed for characterization of piroxicam supersaturation, precipitation, and dissolution in a flow-through setup. A solution of piroxicam dissolved in 1-methyl-2-pyrrolidinone was injected into a flowing aqueous environment (pH 7.4), causing piroxicam to precipitate. Imaging at 405 and 280 nm monitored piroxicam concentration distributions during precipitation and revealed different supersaturation levels dependent on the initial concentration of the piroxicam solution. The combination with imaging at 525 nm, light microscopy, and Raman spectroscopy measurements demonstrated concentration-dependent precipitation and the formation, growth, and dissolution of individual particles. Results emphasize the importance of the specific hydrodynamic conditions on the piroxicam precipitation. The approach used may facilitate comprehensive understanding of drug precipitation and dissolution processes and may be developed further into a basic tool for formulation screening and development.

Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice.

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C, Jadiswami; H M, Megha; Dhadde, Shivsharan B; Durg, Sharanbasappa; Potadar, Pandharinath P; B S, Thippeswamy; V P, Veerapur

2014-12-01

3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington's disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions.

Novel piroxicam-loaded nanospheres generated by the electrospraying technique: physicochemical characterisation and oral bioavailability evaluation.

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Mustapha, Omer; Din, Fakhar Ud; Kim, Dong Wuk; Park, Jong Hyuck; Woo, Kyu Bong; Lim, Soo-Jeong; Youn, Yu Seok; Cho, Kwan Hyung; Rashid, Rehmana; Yousaf, Abid Mehmood; Kim, Jong Oh; Yong, Chul Soon; Choi, Han-Gon

2016-06-01

To determine if a novel electrospraying technique could be applied to an oral drug delivery system for improving the solubility and oral bioavailability of poorly water-soluble piroxicam; the nanospheres were generated with drug and polyvinylpyrrolidone (PVP) using electrospraying technique; and their physicochemical properties, solubility, release and pharmacokinetics were evaluated in comparison with piroxicam powder. All nanospheres had significantly increased drug solubility and dissolution rates in comparison with the drug powder. In particular, the nanosphere composed of piroxicam and PVP at a weight ratio of 2:8 gave about 600-fold higher solubility, 15-fold higher release rate and 3-fold higher AUC in comparison to piroxicam powder, leading to significantly enhanced oral bioavailability in rats, due to the mingled effect of nanonisation along with transformation to the amorphous state. Thus, this electrospraying technique can be utilised to produce a novel oral nanosphere delivery system with enhanced solubility and oral bioavailability for poorly water-soluble piroxicam.

Piroxicam y cambios ováricos de cabras adultas

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Rafaela Segundo Pérez

2016-01-01

Full Text Available La función de los ovarios puede alterarse por inhibidores de la enzima ciclooxigenasa (COX. La aplicación de piroxicam, antiinflamatorio no esteroideo e inhibidor de COX es de amplio uso veterinario (AINE y puede alterar la función de los ovarios. El objetivo de esta investigación fue evaluar los cambios extra e intraováricos en cabras adultas en respuesta a piroxicam. En seis cabras adultas de entre 35 y 40 kg de peso vivo, se sincronizaron estros y ovulación, mediante la colocación de CIDR (dispositivo intravaginal de liberación controlada de P4 durante 11 días, al retirar el CIDR se aplicaron prostaglandinas F2α y 400 UI de eCG (inducción de la ovulación. Antes (24 h, de la inducción de ovulación al grupo testigo y tratado (n=3 se les hicieron cuatro aplicaciones intramusculares de un ml de solución salina o piroxicam (1.5 mg-1 kg de peso vivo con intervalo de 24 h. Posterior a la primera aplicación de piroxicam (144 h se extrajeron los ovarios. Se colectaron muestras sanguíneas cada 24 h; desde 48 h antes de la inducción de la ovulación y, hasta la ovariectomía. En ovario derecho e izquierdo se cuantificó el número y tamaño de folículos y cuerpos lúteos superficiales. En 16 cortes histológicos de cada ovario, se evaluaron las mismas estructuras con localización intraovárica. En suero sanguíneo se determinó la concentración sérica de progesterona (P4 y estradiol (E2. En los datos de folículos y CL se realizó la prueba de suma de rangos de Wilcoxon. Mientras que, P4 y E2 se analizaron utilizando modelos para datos con medidas repetidas (modelos mixtos lineales, los cuales fueron ajustados usando el programa estadísto R. La significancia en los resultados se consideró con α< 0.05. La aplicación de piroxicam disminuyó el número de folículos intraováricos (P< 0.0001 y el de CL intraováricos en desarrollo (P=0.04. Los niveles de P4 y E2 no se modificaron por aplicación de piroxicam (P=0.2, aunque, P4

Protective value of piroxicam on the enhanced inflammatory response after whole body irradiation

Energy Technology Data Exchange (ETDEWEB)

el-Ghazaly, M.; Saleh, S.; Kenawy, S.; Roushdy, H.M.; Khayyal, M.T.

1986-06-01

The anti-inflammatory activity of piroxicam was assessed after whole body irradiation in rats. Two models of inflammation, the carrageenan-induced edema and the adjuvant-induced arthritis in rats have been utilised. Piroxicam at doses of 1, 5 and 10 mg kg-1 i.p. was effective in inhibiting the paw edema produced in both models of inflammation. The inflammatory response in irradiated was significantly higher than that produced in normal animals and was dependent on the radiation dose level used (0.5-2 Gy). The effect of piroxicam on the late inflammatory response produced by exposure to 2 Gy was studied by measuring the carrageenan-induced edema 4 h after irradiation and on the third and seventh day thereafter. The increase in paw volume was significantly suppressed in animals receiving the drug. Administration of piroxicam (5 mg kg-1) one hour before irradiation of animals at 0.5 Gy, produced inhibition to the exaggerated inflammatory response in irradiated animals. This suggests that piroxicam possibly owes its protective value to prevention of the increase in cellular permeability induced by radiation. Alternatively, the drug may exert this effect by inhibiting PG synthesis, thereby reducing their potentiating influence on the other mediators of inflammation. Furthermore, the inhibition of lysosomal enzyme release possibly induced by the drug may contribute to the probable reduction in the release of inflammatory mediators.

Structural and dynamical characterization of piroxicam by 1H- and 13C-NMR relaxation studies

International Nuclear Information System (INIS)

Rossi, C.; Casini, A.; Picchi, M.P.; Laschi, F.; Calabria, A.; Marcolongo, R.

1987-01-01

Carbon spin-lattice relaxation rates of anti-inflammatory drug, piroxicam, have been measured. These results have been used in determining the reorientational rates of the proton carbon vectors. An analysis of internal motions within the pyridinyl moiety of piroxicam was carried out. Selective proton-carbon nuclear Overhauser effect (NOE) measurements were made in order to determine the solution structure of piroxicam. The effect of indirect NOE arising from exchangeable protons has been analyzed and considered. 20 refs.; 4 figs.; 3 tabs

(14) N nuclear quadrupole resonance study of piroxicam: confirmation of new polymorphic form V.

Science.gov (United States)

Lavrič, Zoran; Pirnat, Janez; Lužnik, Janko; Puc, Uroš; Trontelj, Zvonko; Srčič, Stane

2015-06-01

A new polymorphic crystal form of piroxicam was discovered while preparing crystalline samples of piroxicam for (14) N nuclear quadrupole resonance (NQR) analysis. The new crystal form, designated as V, was prepared by evaporative recrystallization from dichloromethane. Three known polymorphic forms (I, II, and III) were also prepared. Our aim was to apply (14) N NQR to characterize the new polymorphic form of piroxicam and compare the results with those of the other known polymorphic forms. Additional analytical methods used for characterization were X-ray powder diffraction (XRPD), thermal analysis, and vibrational spectroscopy. For the first time, a complete set of nine characteristic (14) N NQR frequencies was found for each prepared polymorph of piroxicam. The consistent set of measured frequencies and calculated characteristic quadrupole parameters found for the new polymorphic form V is a convincing evidence that we are dealing with a new form. The already known piroxicam polymorphic forms were characterized similarly. The XRPD results were in accordance with the conclusions of (14) N NQR analysis. The performed study clearly demonstrates a strong potential of (14) N NQR method to be applied as a highly discriminative spectroscopic analytical tool to characterize polymorphic forms. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Effects of piroxicam administration on pregnancy outcome in intrauterine insemination (IUI) cycles: a randomized clinical trial.

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Zarei, A; Mahboubi, M; Parsanezhad, M E; Alborzi, S; Younesi, M; Madadi, G

2016-01-01

Uterus contractibility is considered a powerful prognostic factor in predicting the embryo transfer outcome. Moreover, uterine contractions are known to be stimulated by prostaglandins which are produced by cyclooxygenase from arachidonic acid. As such, suppressing the inflammatory response and contractions using anti-inflammatory and relaxant agents is expected to result in increased success rate of embryo transfer and artificial insemination. To investigate the effect of piroxicam administration on the success rate in intrauterine insemination (IU) cycles in patients presenting with unexplained infertility. This randomized, placebo-controlled clinical trial included 260 women with unexplained infertility undergoing IUI cycles. Patients were randomly assigned to receive either piroxicam ten mg/day on days 4-6 after IUI or placebo (control group). The main outcome measures were number of IUI cycles, pregnancy, abortion, and multiple pregnancy rates. The pregnancy rate was found to be 25 (19.2%) and 16 (12.3%) in piroxicam and control groups, respectively (p = 0.039). Five patients (3.8%) in piroxicam group experienced twin pregnancy whereas only three patients (2.3%) in control group had twin pregnancy (p = 0.361). The pregnancy rate per cycle was also significantly higher in those who received piroxicam as compared to controls (11.16 vs. 6.66; p = 0.021). Administration of piroxicam after IUI is associated with decreased number of cycles, as well as increased pregnancy rate and pregnancy rate per cycle in IUI cycles. However, piroxicam did not have any effect on abortion, multiple pregnancy, and ongoing pregnancy rates.

Risk factors for treatment-related adverse events in cancer-bearing dogs receiving piroxicam.

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Eichstadt, L R; Moore, G E; Childress, M O

2017-12-01

Piroxicam has antitumour effects in dogs with cancer, although side effects may limit its use. The purpose of this study was to retrospectively identify factors predisposing cancer-bearing dogs to adverse events (AEs) following piroxicam therapy. Medical records of dogs presented to the Purdue Veterinary Teaching Hospital between 2005 and 2015 were reviewed, and 137 dogs met the criteria for study inclusion. Toxic effects of piroxicam in these dogs were graded according to an established system. Multivariate logistic regression was used to estimate the extent to which certain factors affected the risk for AEs. Age [odds ratio (OR) 1.250, P = 0.009; 95% confidence interval (CI) 1.057-1.479] and concurrent use of gastroprotectant medications (OR 2.612, P = 0.025; 95% CI 1.127-6.056) significantly increased the risk for gastrointestinal AEs. The results of this study may help inform the risk versus benefit calculation for clinicians considering the use of piroxicam to treat dogs with cancer. © 2016 John Wiley & Sons Ltd.

Double blind comparative study of piroxicam and indomethacin in acute locomotor affections linked with sports activity.

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Commandre, F

1983-01-01

181 patients suffering from acute locomotor affections linked with sports activities were included in a multi-center study. The indications most frequently seen were sprains and tendinitis. 92 patients received piroxicam in a daily dosage of 4 capsules (40 mg) during the first two days, then 20 mg during the following days. 89 patients received a daily dose of indomethacin in a daily dose of 6 capsules (150 mg) for the first two days, and then 100 mg daily thereafter. Treatment lasted from 5 to seven days. Efficacy was judged to be very good or good in 89% of the patients treated with piroxicam against 76% of those treated with indomethacin, a statistically significant difference. Tolerance was also judged better with piroxicam. 4 patients suffered side effects with piroxicam, of which one stopped treatment after the second administration due to allergic reaction. 18 patients treated with indomethacin suffered from side effects, of which 5 stopped the treatment. In total, the use of piroxicam seems particularly interesting in sports medicine in comparison with indomethacin.

Synthesis of new piroxicam derivatives and their influence on lipid bilayers.

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Szczęśniak-Sięga, Berenika; Maniewska, Jadwiga; Poła, Andrzej; Środa-Pomianek, Kamila; Malinka, Wiesław; Michalak, Krystyna

2014-01-01

A novel series of potentially biologically active 1,2-benzothiazine 1,1-dioxides--analogs of piroxicam (a recognized non-steroidal anti-inflammatory drug) were synthesized from commercially available saccharin. All of the synthesized compounds were subjected to preliminary evaluation for their ability to interact with lipid bilayers. The influence of the new derivatives of piroxicam on liposomes made of EYPC was investigated by fluorescence spectroscopy with two fluorescent probes--Laurdan and Prodan. All the studied compounds showed an interaction with model membranes.

Gastrointestinal tolerability of meloxicam and piroxicam: a double-blind placebo-controlled study

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Lipscomb, G R; Wallis, N; Armstrong, G; Rees, W D W

1998-01-01

Aims The aim of the study was to compare the effects of meloxicam and piroxicam on the gastroduodenal mucosa in healthy adults. Methods Forty-four healthy volunteers were given a 28 day course of either meloxicam 15 mg, piroxicam 20 mg or placebo. Damage to the oesophageal, gastric and duodenal mucosa was assessed, mucosal blood flow (MBF) measured at endoscopy and biopsies taken for prostaglandin content and microscopic assessment of damage before NSAID administration and during days 1, 7 and 28 of continued intake. Results Maximal macroscopic gastric mucosal damage (median grade+IQR) occurred within 24 h of piroxicam administration, the damage score increasing from 0 to 2.5 (0–3) (P=0.02) at day 1 before falling to 2.0 (0–2) at day 7 and 0 (0–1) at day 28 with resolution of damage observed in six out of the seven subjects who sustained acute injury. No significant macroscopic gastric damage occurred in either of the two other groups although some minor damage was observed in seven subjects taking placebo and five taking meloxicam. There was a trend towards piroxicam causing more acute gastric damage than meloxicam (P=0.06). Baseline antral, body and duodenal MBF were similar in all three groups. No significant changes occurred in any of the groups on any of the visits. There were also no changes in gastric mucosal prostaglandin content in any group. Conclusions These observations suggest that meloxicam causes little acute damage to the upper gastrointestinal tract and piroxicam causes some acute gastric injury but such damage resolves in most subjects by 28 days. PMID:9723821

The effects of piroxicam and deracoxib on canine mammary tumour cell line.

Science.gov (United States)

Ustün Alkan, Fulya; Ustüner, Oya; Bakırel, Tülay; Cınar, Suzan; Erten, Gaye; Deniz, Günnur

2012-01-01

Cyclooxygenase (COX) inhibitors, already widely used for the treatment of pain and inflammation, are considered as promising compounds for the prevention and treatment of neoplasia. The aim of our study was to determine the direct antiproliferative effects of nonsteroidal anti-inflammatory drugs (NSAIDs), piroxicam and deracoxib, at a variety of concentrations as both single and combined treatments on canine mammary carcinoma cell line CMT-U27 and to understand the mechanisms of cell death. MTT assay was performed to determine cell viability, and flow cytometric analyses were performed to evaluate apoptosis and cell cycle alterations. Significant decrease in cell viability was observed at high concentrations of piroxicam and deracoxib in both single and combined treatments after 72 h incubation. Combined treatment produced a significantly greater inhibition than that caused by either agent alone. Also apoptotic cell number was increased by both drugs at the cytotoxic concentrations. However, concomitant treatment of cells with piroxicam and deracoxib resulted in significant induction of apoptosis at lower concentrations and accumulation of cells in the G₀/G₁ phase. Significant cytotoxic effects exhibited by the combination of piroxicam and deracoxib against canine mammary carcinoma cells in vitro suggest an attractive approach for the treatment of canine mammary carcinoma.

The Effects of Piroxicam and Deracoxib on Canine Mammary Tumour Cell Line

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Fulya Üstün Alkan

2012-01-01

Full Text Available Cyclooxygenase (COX inhibitors, already widely used for the treatment of pain and inflammation, are considered as promising compounds for the prevention and treatment of neoplasia. The aim of our study was to determine the direct antiproliferative effects of nonsteroidal anti-inflammatory drugs (NSAIDs, piroxicam and deracoxib, at a variety of concentrations as both single and combined treatments on canine mammary carcinoma cell line CMT-U27 and to understand the mechanisms of cell death. MTT assay was performed to determine cell viability, and flow cytometric analyses were performed to evaluate apoptosis and cell cycle alterations. Significant decrease in cell viability was observed at high concentrations of piroxicam and deracoxib in both single and combined treatments after 72 h incubation. Combined treatment produced a significantly greater inhibition than that caused by either agent alone. Also apoptotic cell number was increased by both drugs at the cytotoxic concentrations. However, concomitant treatment of cells with piroxicam and deracoxib resulted in significant induction of apoptosis at lower concentrations and accumulation of cells in the G0/G1 phase. Significant cytotoxic effects exhibited by the combination of piroxicam and deracoxib against canine mammary carcinoma cells in vitro suggest an attractive approach for the treatment of canine mammary carcinoma.

Alleviation of glutamate mediated neuronal insult by piroxicam in rodent model of focal cerebral ischemia: a possible mechanism of GABA agonism.

Science.gov (United States)

Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana

2014-12-01

Neurotransmitter imbalance is an inevitable outcome in cerebral ischemia that leads to neuronal death. In the present study, we evaluated the effects of piroxicam, a nonsteroidal anti-inflammatory drug (NSAID), on extracellular brain glutamate and γ-aminobutyric acid (GABA) release, survival time, and neuronal cell death. Transient focal cerebral ischemia in male Charles Foster rat led to neuronal infarction and compromised intrinsic antioxidant status. Thirty-minute preadministration of piroxicam (10 mg/kg b.w.) showed a significant (P piroxicam administration in stroke rat significantly reduced (P piroxicam attenuates extracellular glutamate release and also reduces neuronal cell death due to reduction in oxidative stress in cerebral ischemia. Our results also indicate a consequent increase of extracellular GABA in brain regions administered with piroxicam, which hints that piroxicam alleviates glutamate excitotoxicity possibly by GABA agonism.

Formation of Piroxicam Polymorphism in Solution Crystallization

DEFF Research Database (Denmark)

Bruun Hansen, Thomas; Qu, Haiyan

2015-01-01

also explored, and new insights into polymorphic control are documented and discussed. The crystal landscape was mapped for cooling crystallization of piroxicam from acetone/water mixtures (0.5 K/min) and for antisolvent crystallization from acetone with water as the antisolvent. Varying cooling rates...

Impact of a health safety warning and prior authorisation on the use of piroxicam: a time-series study.

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Carracedo-Martínez, Eduardo; Pia-Morandeira, Agustin; Figueiras, Adolfo

2012-03-01

The aim of this study was to assess the quantitative changes in systemic use of piroxicam after the issue of a health safety warning about its risks and the subsequent implementation of prior authorisation. We determined the number of monthly daily defined doses/1000 inhabitants/day (DHDs) of piroxicam in the period 2005-2008 in a health area in Spain. The data were analysed graphically, and the impact of the safety warning and introduction of prior authorisation were estimated by using segmented regression analysis. The graph showed that the number of DHDs of piroxicam was stable both before and after the health safety warning but registered a very marked decrease after implementation of prior authorisation, after which DHDs of piroxicam remained stable at a 98% inferior level compared with previous to prior authorisation. Segmented regression analysis showed no statistically significant immediate jump in piroxicam utilisation after the safety warning nor a change in the slope afterwards, but it did show a significant immediate jump after prior authorisation. Population exposure to systemic piroxicam remained unaffected by a previous health safety warning but declined sharply after the introduction of prior authorisation. Copyright © 2012 John Wiley & Sons, Ltd.

Bovine lactoferrin and piroxicam as an adjunct treatment for lymphocytic-plasmacytic gingivitis stomatitis in cats.

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Hung, Yi-Ping; Yang, Yi-Ping; Wang, Hsien-Chi; Liao, Jiunn-Wang; Hsu, Wei-Li; Chang, Chao-Chin; Chang, Shih-Chieh

2014-10-01

Feline lymphocytic-plasmacytic gingivitis/stomatitis (LPGS) or caudal stomatitis is an inflammatory disease that causes painfully erosive lesions and proliferations of the oral mucosa. The disease is difficult to cure and can affect cats at an early age, resulting in lifetime therapy. In this study, a new treatment using a combination of bovine lactoferrin (bLf) oral spray and oral piroxicam was investigated using a randomized double-blinded clinical trial in 13 cats with caudal stomatitis. Oral lesion grading and scoring of clinical signs were conducted during and after the trial to assess treatment outcome. Oral mucosal biopsies were used to evaluate histological changes during and after treatment. Clinical signs were significantly improved in 77% of the cats. In a 4-week study, clinical signs were considerably ameliorated by oral piroxicam during the first 2 weeks. In a 12-week study, the combined bLf oral spray and piroxicam, when compared with piroxicam alone, exhibited an enhanced effect that reduced the severity of the oral lesions (P = 0.059), while also significantly improving clinical signs (P piroxicam was safe and might be used to decrease the clinical signs of caudal stomatitis in cats. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Protective effect of antioxidant rich aqueous curry leaf (Murraya koenigii extract against gastro-toxic effects of piroxicam in male Wistar rats

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Syed Benazir Firdaus

2014-01-01

Full Text Available Piroxicam (chemically 4-hydroxy-2-methyl-N-2-pyridinyl-2H-1,2-benzothiazine-3-carboxamide, a classical non-steroidal anti-inflammatory drug (NSAID is orally administered to arthritic patients. Inhibition of prostaglandin E2 (PGE2 synthesis and subsequent free hydroxyl radical generation in vivo exert gastro-toxic side effects on piroxicam treatment. Leaves of curry plant are rich in antioxidants with prolific free radical scavenging activities. This led us to investigate the efficiency of the use of curry leaves in ameliorating piroxicam induced gastric damage. Piroxicam was orally (30 mg per kg body weight administered in male albino Wistar rats to generate gastric ulcers. These rats were orally fed with graded doses of aqueous extract of curry or Murraya koenigii leaves (Cu LE prior to piroxicam administration. Oxidative stress biomarkers, activities of antioxidant and pro-oxidant enzymes, mucin content and nature, PGE2 level, activities of mitochondrial enzymes and histomorphology of gastric tissues were studied. Piroxicam treatment altered all the above mentioned parameters whereas, curry leaf extract pre-treated animals were protected against piroxicam induced alterations. Hence, the protective action of the antioxidant rich Cu LE was investigated to propose a new combination therapy or dietary management to arthritic patients using piroxicam.

Solubility and crystallization of piroxicam from different solvents in evaporative and cooling crystallizations

DEFF Research Database (Denmark)

Qu, Haiyan; Ostergaard, Iben

2018-01-01

polarities; It has been found that the solubility of piroxicam in the solvents is in the following order: chloroform > dichloromethane > acetone > ethyl acetate > acetonitrile > acetic acid > methanol > hexane. Crystallization of piroxicam from different solvents has been performed with evaporative.......Results obtained in the present work showed the stochastic nature of nucleation of different polymorphs as well as the complexity of the crystallization of a polymorphic system....

Sustained release of piroxicam from solid lipid nanoparticle as an effective anti-inflammatory therapeutics in vivo.

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Peng, Li-Hua; Wei, Wei; Shan, Ying-Hui; Chong, Yee-Song; Yu, Lian; Gao, Jian-Qing

2017-01-01

This study aims to investigate the solid lipid nanoparticle (SLN) as a novel vehicle for the sustained release and transdermal delivery of piroxicam, as well as to determine the anti-inflammation effect of piroxicam-loaded SLN. SLN formulation was optimized and the particle size, polydispersity index, zeta potential (ZP), encapsulation efficiency, drug release, and morphological properties were characterized. The transdermal efficiency and mechanism of the piroxicam-loaded SLNs were investigated in vitro. With the inflammation induced edema model in rat, the anti-inflammatory efficiency of piroxicam-enriched SLNs (Pir-SLNs) was evaluated. The SLN formulation was optimized as: lecithin 100 mg, glycerin monostearate 200 mg, and Tween (1%, w/w). The particle size is around 102 ± 5.2 nm with a PDI of 0.262. The ZP is 30.21 ± 2.05 mV. The prepared SLNs showed high entrapment efficiency of 87.5% for piroxicam. There is no interaction between piroxicam and the vehicle components. The presence of polymorphic form of lipid with higher drug content in the optimized Pir-SLNs enables the Pir-SLNs to release the drug with a sustained manner. Pir-SLNs with oleic acid as enhancer can radically diffuse into both the stratum corneum and dermal layer, as well as penetrate through the hair follicles and sebaceous glands with significantly higher density than the other control groups. Pir-SLNs promptly inhibited the inflammation since the 3rd hour after the treatment by decreasing the PGE 2 level. SLN was demonstrated to be a promising carrier for encapsulation and sustained release of piroxicam. Pir-SLN is a novel topical preparation with great potential for anti-inflammation application.

The Effects of Piroxicam in the Attenuation of MPP+/MPTP Toxicity In Vitro and In Vivo

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Soliman, Y.; Jackson, T.; Mazzio, E.

2010-01-01

Several lines of evidence support the neuroprotective action of cyclooxygenase-2 (COX-2) inhibitors in various models of Parkinson's disease (PD). In the current study, we investigated the neuroprotective properties of several COX inhibitors against 1-methyl-4-phenylpyridinium (MPP+) in neuroblastoma Neuro 2A (N-2A) cells in vitro and the protection against degeneration of substantia nigra pars compacta (SNc) dopaminergic (DA) neurons after the administration of 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) in C57/BL6 male mice. The data obtained demonstrate a lack of protective effects observed by COX 1-2 inhibitors ibuprofen and acetylsalicylic acid against MPP+ toxicity in N-2A, where piroxicam was protective in a dose dependent manner (MPP+ control: 15 ± 2% MPP+ piroxicam: 5 mM 89 ± 4%). The data also indicate a drop in mitochondrial oxygen (O2) consumption and ATP during MPP+ toxicity with no restoration of mitochondrial function concurrent to a heightened concentration of somatic ATP during piroxicam rescue. These findings indicate that the neuroprotective effects of COX inhibitors against MPP+ are not consistent, but that piroxicam may work through an unique mechanism to propel anaerobic energy metabolism. On the other hand, using mice, piroxicam (20 mg/kg) was effective against MPTP-induced dopaminergic degeneration in the (SNc) and loss of locomotive function in mice. Administering a 3 day pre-treatment of piroxicam (20 mg/kg) was effective in antagonizing the losses in SNc tyrosine hydroxylase protein expression, SNc DA concentration and associated anomaly in ambulatory locomotor activity. It was concluded from these findings that piroxicam is unique among COX inhibitors in providing very significant neuroprotection against MPP+ in vitro and in vivo. PMID:18612814

Effect of piroxicam, metamizol, and S-adenosylmethionine in a murine model of experimental trichomoniasis

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Nogal-Ruiz J.J.

2005-03-01

Full Text Available Biological effects of piroxicam, metamizol, and S-adenosylmethionine (S-AMET have been tested in NMRI mice infected intraperitoneally with Trichomonas vaginalis. An intraperitoneal treatment during ten preinfection days with piroxicam (10 mg/Kg/day, or metamizol (275 mg/Kg/day, but not with S-AMET (17 mg/Kg/day induced a significant decrease of abdominal lesions and mortality, assessed by means of a pathogenicity index. The trichomonicidal activity of piroxicam, metamizol, and S-AMET was tested in vitro at the concentration of 300 μM, but found ineffective. These assays have shown the usefulness of the experimental trichomoniasis model for the study of the immunomodulating activity of synthetic drugs.

Stability indicating RP-HPLC method for simultaneous determination of piroxicam and ofloxacin in binary combination.

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John, Peter; Azeem, Waqar; Ashfaq, Muhammad; Khan, Islam Ullah; Razzaq, Syed Naeem

2015-09-01

A simple and precise RP-HPLC method was developed for simultaneous determination of piroxicam and ofloxacin in pharmaceutical formulations and human serum. Optimum separations of piroxicam, ofloxacin and stress-induced degradation products were achieved by use of Hypersil BDS C8 column (250 x 4.6mm, 5 μm). The mobile phase was a mixture of acetonitrile: 0.012M K2HPO4: 0.008M sodium citrate (both buffers mixed and pH adjusted to 2.8) (50:25:25 v/v/v) delivered at flow rate of 1.5 mL min⁻¹ using DAD at 254 nm. Response was linear function of concentration over the ranges of 70-130 mg mL⁻¹ for piroxicam and ofloxacin (r² ≥ 0.999). The method efficiently separated the analytical peaks from degradation products with acceptable tailing and resolution. The developed method was successfully used for concurrent analysis of piroxicam and ofloxacin in pharmaceutical formulations, human serum and in vitro drug interaction studies.

Tabletted guar gum microspheres of piroxicam for targeted adjuvant therapy for colonic adenocarcinomas.

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Vats, Anima; Pathak, Kamla

2012-11-01

In recent years, nonsteroidal anti-inflammatory drugs have been found to be cogent as an adjuvant therapeutic agent in mitigating colorectal cancer. Thus, this present investigation was aimed to formulate an oral, targeted tablet of piroxicam microspheres for sustained and targeted adjuvant therapy for colonic adenocarcinomas. Crosslinked guar gum microspheres of piroxicam were directly compressed into matrix tablet and coated with Eudragit S100. The optimized tablet that displayed 0% release in simulated gastric fluid, 15% in simulated intestinal fluid and 97.1% in simulated colonic fluid underwent roentgenographic study in rabbits to check its safe transit to the colon. x-ray images revealed intactness of the tablet until it reached the colon where the tablet matrix eroded. The designed, conceptual formulation emerged as potential carrier for targeted adjuvant therapy of piroxicam.

Piroxicam and C-phycocyanin mediated apoptosis in 1,2-dimethylhydrazine dihydrochloride induced colon carcinogenesis: exploring the mitochondrial pathway.

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Saini, Manpreet Kaur; Sanyal, Sankar Nath; Vaiphei, Kim

2012-04-01

Apoptosis is a synchronized procedure of cell death that is regulated by caspases and proapoptotic proteins. During apoptosis, translocation of cytochrome c, an electron carrier, from mitochondria into the cytosol is regulated by Bcl-2 family members. Cytochrome c in association with an apoptotic protease activating factor (Apaf), a proapoptotic protein essential for cell differentiation and procaspase-9 form the apoptosome complex, which consecutively activates effector caspase, caspase-3, and coordinate the implementation of apoptosis. In the current study, an attempt has been made to gain insight into piroxicam, a traditional nonsteroidal antiinflammatory drug and c-phycocyanin, a biliprotein from Spirulina platensis (cyanobacterium) mediated apoptosis in DMH-induced colon cancer. Male Sprague-Dawley rats were segregated into 5 groups: control, DMH, DMH + piroxicam, DMH + c-phycocyanin, and DMH + piroxicam + c-phycocyanin. Results illustrated that piroxicam and c-phycocyanin treatments stimulate cytochrome c release by downregulating the Bcl-2 (an antiapoptotic protein) expression significantly, while promoting the level of Bax (a proapoptotic protein), thereby activating caspases (caspases-9 and -3) and Apaf-1. The outcomes of the present study clearly signify that piroxicam and c-phycocyanin may mediate mitochondrial-dependent apoptosis in DMH-induced colon cancer. Moreover, apoptosis induction was more apparent in the combination regimen of piroxicam and c-phycocyanin than the individual drugs alone.

Piroxicam immediate release formulations: A fasting randomized open-label crossover bioequivalence study in healthy volunteers.

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Helmy, Sally A; El-Bedaiwy, Heba M

2014-11-01

Piroxicam is a NSAID with analgesic and antipyretic properties, used for the treatment of rheumatoid diseases. The aim of this study was to evaluate the bioequivalence of two brands of piroxicam capsules (20 mg) in 24 Egyptian volunteers. The in vivo study was established according to a single-center, randomized, single-dose, laboratory-blinded, 2-period, 2-sequence, crossover study with a washout period of 3 weeks. Under fasting conditions, 24 healthy male volunteers were randomly selected to receive a single oral dose of one capsule (20 mg) of either test or reference product. Plasma samples were obtained over a 144-hour interval and analyzed for piroxicam by HPLC with UV detection. The pharmacokinetic parameters Cmax , tmax , AUC0-t , AUC0-∞ , Vd /F, Cl/F, and t1/2 were determined from plasma concentration-time profiles. The 90% confidence intervals for the ratio of log transformed values of Cmax , AUC0-t , and AUC0-∞ of the two treatments were within the acceptable range (0.8-1.25) for bioequivalence. From PK perspectives, the two piroxicam formulations were considered bioequivalent, based on the rate and extent of absorption. No adverse events occurred or were reported after a single 20-mg piroxicam and both formulations were well-tolerated. © 2014, The American College of Clinical Pharmacology.

Clinical evaluation of piroxicam-FDDF and azithromycin in the prevention of complications associated with impacted lower third molar extraction.

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Graziani, F; Corsi, L; Fornai, M; Antonioli, L; Tonelli, M; Cei, S; Colucci, R; Blandizzi, C; Gabriele, M; Del Tacca, M

2005-12-01

Combined treatments with non-steroidal anti-inflammatory drugs and antibiotics may offer significant benefits in the prevention of pain and infections associated with oral surgery. In this study, piroxicam and azithromycin were administered to patients undergoing dental extraction to examine the efficacy of piroxicam in the prevention of post-operative pain and inflammatory complications, either in the absence or in the presence of a concomitant antibiotic treatment. Thirty patients were randomly assigned to three groups and treated for 3 days, before impacted lower third molar removal, as follows: (1) sublingual piroxicam-FDDF (fast dissolving dosage formulation) 20 mg/day; (2) oral azithromycin 500 mg/day; (3) piroxicam-FDDF 20 mg/day plus azithromycin 500 mg/day. Oral acetaminophen (500 mg tablets) was allowed as rescue analgesic medication. Pain intensity was evaluated on a 100-mm visual-analogue scale after dental extraction (day 1), and at days 2, 3, 7 after surgery. Edema and trismus were estimated at days 2 and 7. At days 1 and 2, pain intensity was significantly lower in patients treated with piroxicam-FDDF, either alone (p antibiotic may reduce the influence of piroxicam on post-operative inflammation, without affecting its beneficial effect on surgical pain.

Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs.

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Boria, Pedro A; Murry, Daryl J; Bennett, Peter F; Glickman, Nita W; Snyder, Paul W; Merkel, Brenna L; Schlittler, Deborah L; Mutsaers, Anthony J; Thomas, Rose M; Knapp, Deborah W

2004-02-01

To determine the maximum tolerated dose (MTD) of cisplatin administered with piroxicam, the antitumor activity and toxicity of cisplatin combined with piroxicam in dogs with oral malignant melanoma (OMM) and oral squamous cell carcinoma (SCC), and the effects of piroxicam on the pharmacokinetics of cisplatin in dogs with tumors. Prospective nonrandomized clinical trial. 25 dogs. Dogs were treated with a combination of cisplatin (escalating dose with 6 hours of diuresis with saline [0.9% NaCI] solution) and piroxicam (0.3 mg/kg 10.14 mg/lb], PO, q 24 h). The initial cisplatin dose (50 mg/m2) was increased by 5 mg/m2 until the MTD was reached. Tumor stage and size were determined at 6-week intervals during treatment. The pharmacokinetics of cisplatin were determined in dogs receiving a combination of cisplatin and piroxicam during the clinical trial and dogs that were treated with cisplatin alone. 11 dogs with OMM and 9 dogs with SCC were included in the clinical trial. The MTD of cisplatin when administered in combination with piroxicam was 50 mg/m2. Tumor remission occurred in 5 of 9 dogs with SCC and 2 of 11 dogs with OMM. The most common abnormality observed was renal toxicosis. Clearance of cisplatin in dogs that were treated with cisplatin alone was not significantly different from that in dogs treated with a combination of cisplatin and piroxicam. Cisplatin administered in combination with piroxicam had antitumor activity against OMM and SCC. The level of toxicity was acceptable, although renal function must be monitored carefully.

Design, Synthesis, Antinociceptive and Anti-Inflammatory Activities of Novel Piroxicam Analogues

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Eliezer J. Barreiro

2012-11-01

Full Text Available In this paper we report the design, synthesis, antinociceptive and anti-inflammatory activities of a series of benzothiazine N-acylhydrazones 14a–h, planned by structural modification of piroxicam (1, a non steroidal anti-inflammatory drug. Among the synthesized analogues, compounds 14f (LASSBio-1637 and 14g (LASSBio-1639 were identified as novel antinociceptive and anti-inflammatory prototypes, active by oral administration, acting by a mechanism of action that seems to be different from that of piroxicam, since they were inactive as an inhibitor of cyclooxygenase (COX-1 and COX-2 at concentrations of 10 mM.

Design, synthesis, antinociceptive and anti-inflammatory activities of novel piroxicam analogues.

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de Miranda, Amanda Silva; Bispo Júnior, Walfrido; da Silva, Yolanda Karla Cupertino; Alexandre-Moreira, Magna Suzana; Castro, Rosane de Paula; Sabino, José Ricardo; Lião, Luciano Morais; Lima, Lídia Moreira; Barreiro, Eliezer J

2012-11-28

In this paper we report the design, synthesis, antinociceptive and anti-inflammatory activities of a series of benzothiazine N-acylhydrazones 14a–h, planned by structural modification of piroxicam (1), a non steroidal anti-inflammatory drug. Among the synthesized analogues, compounds 14f (LASSBio-1637) and 14g (LASSBio-1639) were identified as novel antinociceptive and anti-inflammatory prototypes, active by oral administration, acting by a mechanism of action that seems to be different from that of piroxicam, since they were inactive as an inhibitor of cyclooxygenase (COX-1 and COX-2) at concentrations of 10 mM.

Aquaporin-4 inhibition mediates piroxicam-induced neuroprotection against focal cerebral ischemia/reperfusion injury in rodents.

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Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana; Yavagal, Dileep R

2013-01-01

Aquaporin-4(AQP4) is an abundant water channel protein in brain that regulates water transport to maintain homeostasis. Cerebral edema resulting from AQP4 over expression is considered to be one of the major determinants for progressive neuronal insult during cerebral ischemia. Although, both upregulation and downregulation of AQP4 expression is associated with brain pathology, over expression of AQP4 is one of the chief contributors of water imbalance in brain during ischemic pathology. We have found that Piroxicam binds to AQP4 with optimal binding energy value. Thus, we hypothesized that Piroxicam is neuroprotective in the rodent cerebral ischemic model by mitigating cerebral edema via AQP4 regulation. Rats were treated with Piroxicam OR placebo at 30 min prior, 2 h post and 4 h post 60 minutes of MCAO followed by 24 hour reperfusion. Rats were evaluated for neurological deficits and motor function just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, biochemical analysis, RT-PCR and western blot experiments. Piroxicam pretreatment thirty minutes prior to ischemia and four hour post reperfusion afforded neuroprotection as evident through significant reduction in cerebral infarct volume, improvement in motor behavior, neurological deficit and reduction in brain edema. Furthermore, ischemia induced surge in levels of nitrite and malondialdehyde were also found to be significantly reduced in ischemic brain regions in treated animals. This neuroprotection was found to be associated with inhibition of acid mediated rise in intracellular calcium levels and also downregulated AQP4 expression. Findings of the present study provide significant evidence that Piroxicam acts as a potent AQP4 regulator and renders neuroprotection in focal cerebral ischemia. Piroxicam could be clinically exploited for the treatment of brain stroke along with other anti-stroke therapeutics in future.

Formulation and evaluation of sublingual delivery of piroxicam using thermosensitive polymer with an inverted Franz diffusion cell.

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Sivaraman, Arunprasad; Banga, Ajay K

2016-01-01

The aim of the study was to prepare a sublingual formulation for piroxicam using a thermosensitive polymer and to evaluate its permeation through porcine sublingual mucosa. Formulation technique utilized the transition property of poloxamer from solution state at room temperature to gel state at oromucosal temperature (37 °C). The permeation of the drug was evaluated using an inverted Franz diffusion cell technique that allowed the dosage form to be directly applied onto the substrate with required volume of saliva. The formulation was characterized for microscopy of the piroxicam crystals, sol-gel transition property and in-vitro diffusion study. Poloxamer-based formulation enhanced solubility and increased permeability of the piroxicam. Poloxamer formulation with 0.1% w/w piroxicam delivered a cumulative amount of 11.99 ± 7.82 and 11.23 ± 1.79 μg/cm(2), while non-poloxamer formulation delivered 3.57 ± 2.20 and 4.60 ± 6.90 μg/cm(2) with 0.1 and 0.5 ml artificial saliva, respectively, through porcine sublingual tissue in 6 h. A similar delivery profile was observed for 0.05% w/w piroxicam formulation as well. © 2015 Royal Pharmaceutical Society.

Inflammatory mammary carcinoma in 12 dogs: Clinical features, cyclooxygenase-2 expression, and response to piroxicam treatment

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de M. Souza, Carlos H.; Toledo-Piza, Evandro; Amorin, Renee; Barboza, Andrigo; Tobias, Karen M.

2009-01-01

Canine inflammatory mammary carcinoma (IMC) is a rare, locally aggressive, highly metastatic tumor that is poorly responsive to treatment. The purposes of this study were to retrospectively evaluate the history, signalment, and clinical signs of dogs with IMC; compare the outcome of affected dogs treated with traditional chemotherapy with those treated with piroxicam; evaluate Cox-2 expression of IMC cells; and correlate Cox-2 expression with outcome based on treatment. Strong cyclooxygenase-2 expression was present in all tumors. Improvement in clinical condition and disease stability was achieved in all dogs treated with piroxicam, with mean and median progression-free survival of 171 and 183 days, respectively. Median survival time of 3 dogs treated with doxorubicin-based protocols was 7 days, which was significantly less than that of dogs treated with piroxicam (median, 185 days). In conclusion, piroxicam should be considered as a single agent for the treatment of dogs with inflammatory mammary carcinoma. PMID:19436636

Piroxicam-Induced hepatic and renal Histopathological changes in mice

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Amany Tohamy

2007-02-01

Full Text Available Piroxicam is a non-steroidal anti-inflammatory drug widely used in rheumatic diseases. The aim of this study was to investigate Piroxicam-induced histopathological changes in livers and kidneys of male albino mice. Methods: Animals were classified into a control group and 4 treated groups. Piroxicam was injected intraperitoneally using 0.3 mg/kg every day for four weeks. Each week a group of mice was sacrificed. Liver and kidneys were obtained for histological and histochemical examination.Animals were classified into a control group and 4 treated groups. Piroxicam was injected intraperitoneally using 0.3 mg/kg every day for four weeks. Each week a group of mice was sacrificed. Liver and kidneys were obtained for histological and histochemical examination.Results: Liver sections appeared with inflammatory cellular infiltration, vacuolated hepatocytes, dilated sinusoids, and increased number of Kupffer cells. Kidney sections appeared with some cellular inflammations. The glomeruli were shrunk resulting in widening of the urinary space. Oedema and vacuolations were noticed in the tubular cells. There was a positive correlation between these pathological changes and the increased treatment periods. Histochemical staining revealed that glycogen and protein contents had decreased in the hepatocytes. This depletion worsened gradually in liver cells after two, three, and four weeks. Similar depletion of the glycogen content was observed in kidney tissue. However, protein content appeared to be slightly decreased in the kidney tubules and glomeruli. Incensement of coarse chromatin in the nuclei of hepatocytes, Kupffer cells and most inflammatory cells were detected by Fuelgen method. Kidney tissues appeared with a severe decrease in coarse chromatin in the nuclei.Liver sections appeared with inflammatory cellular infiltration, vacuolated hepatocytes, dilated sinusoids, and increased number of Kupffer cells. Kidney sections appeared with some cellular

Potentiometric pKa Determination of Piroxicam and Tenoxicam in Acetonitrile-Water Binary Mixtures

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Çubuk Demiralay, Ebru; Yılmaz, Hülya

2012-01-01

Abstract: Ionization constant (pKa) is one among the parameter to be estimated with accuracy, irrespective of solubility constraints. In the present study, acid-base behaviour of the piroxicam and tenoxicam was studied. By using the potentiometric method, pKa values of piroxicam and tenoxicam have been determined in different percentage of acetonitrile-water binary mixtures (acetonitrile content between 30 and 45% in volume). Aqueous pKa values of these compounds were calculated by mole fract...

Qualitative and Quantitative Evaluation of Multi-source Piroxicam ...

African Journals Online (AJOL)

The qualitative and quantitative evaluation of eleven brands of piroxicam capsules marketed in Nigeria is presented. The disintegration time, dissolution rate and absolute drug content were determined in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF) without enzymes. Weight uniformity test was also ...

Molecular analysis of the effects of Piroxicam and Cisplatin on mesothelioma cells growth and viability

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Verdina, Alessandra; Cardillo, Irene; Nebbioso, Angela; Galati, Rossella; Menegozzo, Simona; Altucci, Lucia; Sacchi, Ada; Baldi, Alfonso

2008-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed for prevention and treatment of a variety of human cancers. Piroxicam, in particular, has been recently shown to exert significant anti-tumoral activity in combination with cisplatin (CDDP) on mesothelioma cells. However, the mechanisms through which NSAIDs regulate the cell cycle as well as the signal pathways involved in the growth inhibition, remain unclear. In the present study, using two mesothelioma cell lines, MSTO-211H and NCI-H2452, we have investigated the influence of piroxicam alone and in association with CDDP on proliferation, cell cycle regulation and apoptosis. In both cell lines a significant effect on cell growth inhibition, respect to the control, was observed with all the drugs tested. Moreover, treatment with piroxicam or CDDP alone altered the cell cycle phase distribution as well as the expression of some cell cycle regulatory proteins in both cell lines. These effects were increased, even if in a not completely overlapping manner, after treatment with the association of piroxicam and CDDP. In particular, the two drugs in NCI cell line had a synergistic effect on apoptosis, probably through activation of caspase 8 and caspase 9, while the most evident targets among the cell cycle regulators were cyclin D1 and p21waf1. These results suggest that the association of piroxicam and CDDP specifically triggers cell cycle regulation and apoptosis in different mesothelioma cell lines and may hold promise in the treatment of mesothelioma. PMID:18498639

Development and characterization of solid dispersion of piroxicam for improvement of dissolution rate using hydrophilic carriers

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Mohammad Barzegar-jalali

2014-09-01

Full Text Available Introduction: The main objective of this study was preparation and characterization of solid dispersion of piroxicam to enhance its dissolution rate. Methods: Solid dispersion formulations with different carriers including crospovidone, microcrystalline cellulose and Elaeagnus angustifolia fruit powder and with different drug: carrier ratios were prepared employing cogrinding method. Dissolution study of the piroxicam powders, physical mixtures and solid dispersions was performed in simulated gastric fluid and simulated intestinal fluid using USP Apparatus type II. The physical characterization of formulations were analyzed using powder X ray diffraction (PXRD, particle size analyzer and differential scanning calorimetry (DSC. Interactions between the drug and carriers were evaluated by Fourier transform infrared (FT-IR spectroscopic method. Results: It was revealed that all of three carriers increase the dissolution rate of piroxicam from physical mixtures and especially in solid dispersions compared to piroxicam pure and treated powders. PXRD and DSC results were confirmed the reduction of crystalline form of piroxicam. FT-IR analysis did not show any physicochemical interaction between drug and carriers in the solid dispersion formulations. Conclusion: Dissolution rate was dependent on the type and ratio of drug: carrier as well as pH of dissolution medium. Dissolution data of formulations were fitted well in to the linear Weibull as well as non-linear logistic and a suggested models.

Evaluation of piroxicam-β-cyclodextrin as a preemptive analgesic in functional endoscopic sinus surgery

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G.T. Keleş

2010-08-01

Full Text Available The preemptive analgesic efficacy and adverse effects of preoperatively administered piroxicam-β-cyclodextrin for post-endoscopic sinus surgery pain was determined in a prospective, double-blind, randomized, clinical study. Seventy-five American Society of Anesthesiologists status I-II patients, aged 18-65 years, were divided into three groups with similar demographic characteristics: group 1 received 20 mg piroxicam-β-cyclodextrin, group 2 received 40 mg piroxicam-β-cyclodextrin and group 3 received placebo orally before induction of general anesthesia. A blinded observer recorded the incidence and severity of pain at admission to the post-anesthesia care unit (PACU, at 15, 30, and 45 min in the PACU, and 1, 2, 4, 6, and 24 h postoperatively. All patients received patient-controlled morphine analgesia during the postoperative period and consumption was recorded for 24 h. During the PACU period, mean visual analogue scale values were significantly lower in groups 1 and 2 compared to group 3 (P < 0.05. During the postoperative period, morphine consumption was 3.03 ± 2.54, 2.7 ± 2.8, and 5.56 ± 3.12 mg for each group, respectively (P < 0.05. As a side effect, bleeding was observed in groups 1 and 3, nausea and vomiting in all groups, and edema only in group 3. However, no significant differences were detected in any of the parameters analyzed, which also included epigastric pain, constipation/diarrhea and headache. Similar hematological test results were obtained for all groups. Preemptive administration of piroxicam-β-cyclodextrin effectively reduced analgesic consumption, and 40 mg of the drug was more effective than 20 mg piroxicam-β-cyclodextrin without side effects during the postoperative period.

Combination therapy of ifenprodil with piroxicam may be an effective therapeutic intervention in cerebral stroke: a hypothesis.

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Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana

2012-10-01

Owing to the intricate and multifaceted pathology of cerebral stroke, multiple drug therapy had long been suggested for effective stroke treatment. Therefore, the development of a potential new combination of drug is necessitated which can bring about desirable improved neuroprotection targeting different pathways against ischemic stroke. In this context, we hypothesize the combination effect of Piroxicam, a Non steroidal anti inflammatory drug with Ifenprodil, a NR2b selective NMDAR antagonist in animal model of cerebral ischemia. A few past studies have enumerated the neuroprotective roles of Piroxicam and Ifenprodil administered in singlet against cerebral ischemia in animal model, hence we hypothesized that by using Piroxicam and Ifenprodil in combination would provide additive neuroprotection than either of the agents used alone. In this article, we discuss our hypothesis regarding the possibility of Piroxicam and Ifenprodil as a potent combination which may have a positive therapeutic role in treatment of cerebral ischemia through its anti-inflammatory, anti-apoptotic and anti-oxidative characteristics of Piroxicam with Ifenprodil which has been proved to have neuroprotective, anticonvulsant and antinociceptive effects and has potentials for the treatment of several neuropsychiatric disorders, such as Parkinson's disease alcoholism and drug addiction. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effect of virgin olive oil versus piroxicam phonophoresis on exercise-induced anterior knee pain.

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Nakhostin-Roohi, Babak; Khoshkhahesh, Faegheh; Bohlooli, Shahab

2016-01-01

The main purpose of this study was to evaluate the effects of virgin olive oil phonophoresis on female athletes' anterior knee pain (AKP). A double blinded randomized clinical trial was conducted. Ninety-three female athletes suffering from AKP voluntarily participated in this study. Patients were randomly assigned into olive oil (n=31), piroxicam (n=31) or base gel phonophoresis (n=31) groups. At the baseline visit, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire was filled by subjects who were then treated with olive oil, piroxicam or pure phonophoresis for 12 sessions. After 6 and 12 sessions of physiotherapy, subjects filled the questionnaire again. Main outcomes were significant improvement in pain, stiffness, physical function, and total WOMAC scores. Although, there was a significant reduction in symptoms of AKP at the end of the therapy in all groups (pgroup, this improvement was seen after 6 sessions of treatment (pgroup and piroxicam and/or phonophoresis group was observed after 6 sessions of therapy (pvirgin olive oil is as effective as piroxicam gel on lowering WOMAC scores of AKP in female athletes and also has several beneficial properties including faster effect and shorter duration of therapy. The exact mechanism of beneficial action of virgin olive oil on AKP is not clear and requires further studies.

Enhancement of dissolution rate of piroxicam by electrospinning technique

International Nuclear Information System (INIS)

Begum, S K Raziya; Varma, M Mohan; Raju, D B; Prasad, R G S V; Phani, A R; Jacob, Biju; Salins, Paul C

2012-01-01

The use of electrospun nanofibers to enhance dissolution of poorly soluble drugs could be a novel strategy in future for pharmaceutical applications. In the present work electrospun nanofibers were prepared as a novel system for enhancing the delivery of piroxicam, a non-steroidal anti-inflammatory drug (NSAID). These nanofibers were prepared from polyvinyl pyrrolidone (PVP) (pharmaceutical grade), a biodegradable polymer, to obtain a solution with drug:polymer ratio of 1:4. The release rate of the piroxicam nanofibers was studied in simulated gastric fluid. Fourier transform infrared (FTIR) and scanning electron microscopy (SEM) are used to evaluate the chemical and physical nature. The results showed that the release rates were twice increased in comparison with the pure drug. However, the blend of drug and polymer could be varied to optimize the release rates depending upon the need and formulation (paper)

Enhancement of dissolution rate of piroxicam by electrospinning technique

Science.gov (United States)

Raziya Begum, S. K.; Mohan Varma, M.; Raju, D. B.; Prasad, R. G. S. V.; Phani, A. R.; Jacob, Biju; Salins, Paul C.

2012-12-01

The use of electrospun nanofibers to enhance dissolution of poorly soluble drugs could be a novel strategy in future for pharmaceutical applications. In the present work electrospun nanofibers were prepared as a novel system for enhancing the delivery of piroxicam, a non-steroidal anti-inflammatory drug (NSAID). These nanofibers were prepared from polyvinyl pyrrolidone (PVP) (pharmaceutical grade), a biodegradable polymer, to obtain a solution with drug:polymer ratio of 1:4. The release rate of the piroxicam nanofibers was studied in simulated gastric fluid. Fourier transform infrared (FTIR) and scanning electron microscopy (SEM) are used to evaluate the chemical and physical nature. The results showed that the release rates were twice increased in comparison with the pure drug. However, the blend of drug and polymer could be varied to optimize the release rates depending upon the need and formulation

Aminopropyl groups of the functionalized Mobil Crystalline Material 41 as a carrier for controlled diclofenac sodium and piroxicam delivery.

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Khodaverdi, Elham; Ahmadi, Mina; Kamali, Hossein; Hadizadeh, Farzin

2017-01-01

Synthetic Mobil Crystalline Material 41 (MCM-41) as a mesoporous material and functionalized MCM-41 using aminopropyl groups were studied in order to investigate their ability to encapsulate and to control the release of diclofenac sodium and piroxicam. MCM-41 was synthesized through sol-gel procedure and functionalized with aminopropyl groups. The physicochemical properties of MCM-41 were studied through particle size analysis, infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and carbon-hydrogen-nitrogen analysis. Diclofenac sodium and piroxicam were loaded into the MCM-41 matrix using the filtration and solvent evaporation methods. The drug-loading capacity was determined by ultraviolet, Fourier transform infrared, X-ray diffraction, and Brunauer-Emmett-Teller analysis. According to the results for pure drug release, >57% was released in the 1 st h, but when these drugs were loaded into pure Mobil Crystalline Material 41 (MCM-41) and functionalized MCM-41, the release into the simulated gastrointestinal medium was less, continuous, and slower. The release of piroxicam from functionalized MCM-41 was slower than that from MCM-41 in the simulated intestinal medium because of the formation of electrostatic bonds between piroxicam and the aminopropyl groups of the functionalized MCM-41. However, in the case of diclofenac sodium, there was no significant difference between pure MCM-41 and functionalized MCM-41. The difference between piroxicam and diclofenac sodium was due to the high solubility of diclofenac sodium in the intestinal medium (pH 6.8), which caused more rapid release from the matrixes than for piroxicam. Our findings indicate that, after functionalization of MCM-41, it could offer a good means of delivering controlled diclofenac sodium and piroxicam.

Mechanisms Involved in Toxicity of Liver Caused by Piroxicam in Mice and Protective Effects of Leaf Extract of Hibiscus Rosa-Sinensis L.

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C. R. Sahu

2016-01-01

Full Text Available Piroxicam is one of the important therapeutic nonsteroidal anti-inflammatory class of drugs used mainly to suppress pain and inflammation in arthritis and other musculoskeletal disorders. Besides being anti-inflammatory, these drugs are analgesic and antipyretic often used for the relief of nonspecific fever condition. Recently, piroxicam has also gained attention as an effective therapy for tumors, colorectal, and invasive bladder cancers. The objective of the current study is to evaluate the protective effects of the alcoholic leaf extract of Hibiscus rosa-sinensis (AEH, Malvaceae, against piroxicam-induced toxicity in mice. Sixty adult Swiss albino mice ( Mus musculus were divided into four groups ( n = 10, which included a control group, a group treated orally with AEH (30 mg kg –1 b.w. for 15 days, a group treated orally with piroxicam (6.6 mg kg –1 b.w. for 15 days, and another group treated orally with piroxicam and AEH for 15 days. The results indicated that treatment with piroxicam alone resulted in a significant increase in the activities of serum marker enzymes, namely, aspartate transaminase, alanine transaminase, and alkaline phosphatase with profound hepatic lipid peroxidation as evidenced by a marked increment in the level of thoibarbituric acid reactive substances along with a distinct diminution in reduced glutathoine content and various antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase in the liver. However, treatment with AEH during piroxicam treatment retrieved or partially antagonized the effects induced by piroxicam toward the normal values of controls. Histopathological observations also corroborate with the above findings. It can be concluded that AEH exhibited a protective action against piroxicam toxicity and effective in combating oxidative stress-induced hepatic damage.

Interaction of a common painkiller piroxicam and copper-piroxicam with chromatin causes structural alterations accompanied by modulation at the epigenomic/genomic level.

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Goswami, Sathi; Sanyal, Sulagna; Chakraborty, Payal; Das, Chandrima; Sarkar, Munna

2017-08-01

NSAIDs are the most common class of painkillers and anti-inflammatory agents. They also show other functions like chemoprevention and chemosuppression for which they act at the protein but not at the genome level since they are mostly anions at physiological pH, which prohibit their approach to the poly-anionic DNA. Complexing the drugs with bioactive metal obliterate their negative charge and allow them to bind to the DNA, thereby, opening the possibility of genome level interaction. To test this hypothesis, we present the interaction of a traditional NSAID, Piroxicam and its copper complex with core histone and chromatin. Spectroscopy, DLS, and SEM studies were applied to see the effect of the interaction on the structure of histone/chromatin. This was coupled with MTT assay, immunoblot analysis, confocal microscopy, micro array analysis and qRT-PCR. The interaction of Piroxicam and its copper complex with histone/chromatin results in structural alterations. Such structural alterations can have different biological manifestations, but to test our hypothesis, we have focused only on the accompanied modulations at the epigenomic/genomic level. The complex, showed alteration of key epigenetic signatures implicated in transcription in the global context, although Piroxicam caused no significant changes. We have correlated such alterations caused by the complex with the changes in global gene expression and validated the candidate gene expression alterations. Our results provide the proof of concept that DNA binding ability of the copper complexes of a traditional NSAID, opens up the possibility of modulations at the epigenomic/genomic level. Copyright © 2017 Elsevier B.V. All rights reserved.

Nanoemulsifying drug delivery system to improve the bioavailability of piroxicam.

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Motawea, Amira; Borg, Thanaa; Tarshoby, Manal; Abd El-Gawad, Abd El-Gawad H

2017-05-01

The aim of this study is to develop and characterize self-nanoemulsifying drug delivery system (SNEDDS) of piroxicam in liquid and solid forms to improve its dissolution, absorption and therapeutic efficacy. The generation of liquid SNEDDS (L-SNEDDS) was composed of soybean or coconut oil/Tween 80/Transcutol HP (12/80/8%w/w) and it was selected as the optimized formulation based on the solubility study and pseudo-ternary phase diagram. Optimized L-SNEDDS and liquid supersaturatable SNEDDS (L-sSNEDDS) preparations were then adsorbed onto adsorbents and formulated as directly compressed tablets. The improved drug dissolution rate in the solid supersaturatable preparation (S-sSNEDDS) may be due to the formation of a nanoemulsion and the presence of drug in an amorphous state with hydrogen bond interaction between the drug and SNEDDS components. In vivo pharmacokinetic studies on eight healthy human volunteers showed a significant improvement in the oral bioavailability of piroxicam from S-sSNEDDS (F12) compared with both the pure drug (PP) and its commercial product (Feldene ® ) (commercial dosage form (CD)). The relative bioavailability of S-sSNEDDS (F12) relative to PP or CD was about 151.01 and 98.96%, respectively. The obtained results ratify that S-sSNEDDS is a promising drug delivery system to enhance the oral bioavailability of piroxicam.

A comparative study of efficacy and safety of flupirtine versus piroxicam in postoperative pain in patients undergoing lower limb surgery

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Chinnaiyan S

2017-10-01

Full Text Available Sowmya Chinnaiyan,1 Narayana Sarala,1 Heddur Shanthappa Arun2 1Department of Pharmacology, 2Department of Orthopaedics, Sri Devaraj Urs Medical College, Sri Devaraj Urs Academy of Higher Education and Research, Kolar, Karnataka, India Background: Effective control of pain postoperatively is essential in providing enhanced patient care and a cost-effective hospital stay. Though many treatment modalities exist for postoperative pain management in orthopedic surgeries they are often accompanied by adverse effects. This study was carried out to assess the efficacy of flupirtine and piroxicam in postoperative pain reduction using visual analog scale (VAS score. Materials and methods: An open-label, parallel group, comparative study was conducted on patients undergoing lower limb orthopedic surgery, randomized into two groups of 38 patients each. They received either flupirtine 100 mg or piroxicam 20 mg 6 hours after surgery and then twice daily orally for 5 days. Pain was measured using VAS score, total pain relief score (TOTPAR24, and patient satisfaction score (PSS; the other scales used were behavioral pain assessment scale (BPAS and functional activity score (FAS. Rescue medication used was tramadol 100 mg intravenously. WHO causality scale was used for assessing adverse effects. Descriptive and inferential statistics were used for assessment of various parameters. Results: A total of 76 patients with mean ± standard deviation age of 35.08±10.3 years were recruited; 34 in the flupirtine and 37 in the piroxicam groups completed the study. Patients in both groups were comparable in baseline characteristics. Flupirtine and piroxicam reduced VAS score 48 hours postoperatively compared to baseline (p=0.006 and 0.001 and piroxicam produced significant reduction in pain at 8, 12, and 120 hours compared to flupirtine (p=0.028, 0.032, 0.021. TOTPAR24 and PSS at 24 hours were comparable between the treatments. BPAS scores at 24 hours were reduced

Predictive validity and immune cell involvement in the pathogenesis of piroxicam-accelerated colitis in interleukin-10 knockout mice

DEFF Research Database (Denmark)

Holgersen, Kristine; Kvist, Peter Helding; Hansen, Axel Jacob Kornerup

2014-01-01

Piroxicam administration is a method for induction of enterocolitis in interleukin-10 knockout (IL-10 k.o.) mice. The piroxicam-accelerated colitis (PAC) IL-10 k.o. model combines a dysregulated immune response against the gut microbiota with a decreased mucosal integrity. The predictive validity...... and pathogenic mechanisms of the model have not been thoroughly investigated. In this study, IL-10 k.o. mice received piroxicam in the chow, and model qualification was performed by examining the efficacy of prophylactic anti-IL-12/23p40 monoclonal antibody (mAb), anti-TNFαmAb, cyclosporine A (CsA) and oral...

Efficacy of piroxicam plus cisplatin-loaded PLGA nanoparticles in inducing apoptosis in mesothelioma cells.

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Menale, Ciro; Piccolo, Maria Teresa; Favicchia, Ilaria; Aruta, Maria Grazia; Baldi, Alfonso; Nicolucci, Carla; Barba, Vincenzo; Mita, Damiano Gustavo; Crispi, Stefania; Diano, Nadia

2015-02-01

Combined treatment based on cisplatin-loaded Poly(D,L-lactic-co-glicolic)acid (PLGA) nanoparticles (NP-C) plus the NSAID piroxicam was used as novel treatment for mesothelioma to reduce side effects related to cisplatin toxicity. PLGA nanoparticles were prepared by double emulsion solvent evaporation method. Particle size, drug release profile and in vitro cellular uptake were characterized by TEM, DLS, LC/MS and fluorescence microscopy. MSTO-211H cell line was used to analyse NP-C biological efficacy by FACS and protein analysis. Cisplatin was encapsulated in 197 nm PLGA nanoparticles with 8.2% drug loading efficiency and 47% encapsulation efficiency. Cisplatin delivery from nanoparticles reaches 80% of total encapsulated drug in 14 days following a triphasic trend. PLGA nanoparticles in MSTO-211H cells were localized in the perinuclear space NP-C in combination with piroxicam induced apoptosis using a final cisplatin concentration 1.75 fold less than free drug. Delivered cisplatin cooperated with piroxicam in modulating cell cycle regulators as caspase-3, p53 and p21. Cisplatin loaded PLGA nanoparticles plus piroxicam showed a good efficacy in exerting cytotoxic activity and inducing the same molecular apoptotic effects of the free drugs. Sustained cisplatin release allowed to use less amount of drug, decreasing toxic side effects. This novel approach could represent a new strategy for mesothelioma treatment.

PEMBUATAN DAN UJI AKTIVITAS SEDIAAN GEL SCARLESS WOUND DENGAN EKSTRAK BINAHONG DAN ZAT AKTIF PIROXICAM

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Ayaga Divadi

2016-06-01

Full Text Available Wound is a condition where the tissue integrity is damaged so that body will attempt to repair the damaged tissue by wound healing mechanism. This mechanism usually results in the scar formed by its inflammatory phase. Binahong (Anredera cordifolia (Ten. Steenis contains ascorbic acid and flavonoids which are important for collagen formation, to improve the rate of the wound healing process. Piroxicam can shorten or detain the inflammatory phase by inhibiting the cyclooxygenase (COX enzymes in the prostaglandine synthesis process, which play an important role in scar formation. The aim of this research is to discover if the combination of piroxicam and binahong extract in the scarless wound gel could offer scar reduction effect. In this research, a gel preparation with binahong extract was combined with piroxicam to develop the scarless wound gel (BinPirox. The research was purely experimental. It was done by conducting a histopathological test followed by collagen area calculation. The data were analyzed by independent sample t-test with 95% significancy level. In this research, the addition of piroxicam was expected to reduce the scar formation on incisional wound of white Swiss Webster mice (Mus musculus. The result showed that BinPirox formed statistically less scar when compared to Bin (a gel preparation with binahong extract.

Anti-tumour efficacy of etoposide alone and in combination with piroxicam against canine osteosarcoma in a xenograft model.

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Ong, S M; Saeki, K; Kok, M K; Tanaka, Y; Choisunirachon, N; Yoshitake, R; Nishimura, R; Nakagawa, T

2017-08-01

Osteosarcoma (OSA) in dogs is locally invasive and highly malignant. Distant metastasis is the most common cause of death. To date, the survival rate in dogs with OSA remains poor. The cytotoxic effects of etoposide against canine OSA cell lines, either alone or in combination with piroxicam, have been previously demonstrated in vitro. The aim of this study was to evaluate the anti-tumour effect of etoposide alone and in combination with piroxicam on canine OSA using murine models. Etoposide single agent treatment significantly delayed tumour progression with a marked reduction in Ki-67 immunoreactivity in tumour tissue. Concomitant treatment with piroxicam did not enhance the anti-tumour efficacy of etoposide. Etoposide single agent treatment and combination treatment with piroxicam down-regulated survivin expression, but was not followed by increased apoptotic activity. These findings indicate that etoposide might be a promising novel therapeutic for canine OSA. Further investigations into its potential for clinical application in veterinary oncology are warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reproductive studies with the anti-inflammatory agent, piroxicam: modification of classical protocols.

Science.gov (United States)

Perraud, J; Stadler, J; Kessedjian, M J; Monro, A M

1984-02-14

Reproductive toxicology studies were conducted in rabbits and rats given piroxicam, a non-steroidal anti-inflammatory agent (NSAI), orally at 2, 5 and 10 mg/kg/day. In teratology studies there was neither drug-related embryotoxicity nor teratogenicity. As piroxicam, like other NSAI, affects parturition in rats and leads to a progressive toxicity in lactating females, standard protocols were modified: dams of the female fertility study were treated from 2 weeks prior to mating until day 6 of gestation and females of the post-natal toxicity study were treated from parturition until day 12 of lactation. No other adverse effects on reproduction, fertility and postnatal development were observed.

Optimization and formulation design of carbopol loaded Piroxicam gel using novel penetration enhancers.

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Chaudhary, Hema; Rohilla, Ajay; Rathee, Permender; Kumar, Vikash

2013-04-01

The aim of the study was to develop and optimize Piroxicam transdermal gel formulation using three-factor, three-level Box-Behnken design by deriving a second-order polynomial equation to construct contour plots for prediction of responses as three selected independent variables with ratio of carbopol 974 (X1), ratio of propylene glycol (PG) (X2) and ratio of ethanol (X3). The dependent variables studied were the skin permeation rate of piroxicam (Y1), viscosity of the gel (Y2) and pH of the gel (Y3). Response surface plots were drawn, statistical validity of the polynomials was established to find the compositions of optimized formulation which was evaluated using the vertical Franz-type diffusion cell. The permeation rate of piroxicam increased proportionally with ethanol concentration but decreased with polymer concentration. The design demonstrated the role of the derived polynomial equation and contour plots in predicting the values of dependent variables for the preparation and optimization of gel formulation. Copyright © 2013 Elsevier B.V. All rights reserved.

Mast cells are critical for protection against peptic ulcers induced by the NSAID piroxicam.

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Daniel D Hampton

Full Text Available Many commonly used non-steroidal anti-inflammatory drugs (NSAIDs also cause gastrointestinal toxicity, including the development of life-threatening peptic ulcers. We report that mast cell-deficient mice have an extremely high incidence of severe peptic ulceration when exposed to the NSAID piroxicam. This enhanced ulcer susceptibility can be reversed by reconstitution with mast cells. Furthermore, wild type mice treated with diphenhydramine hydrochloride, a commonly used antihistamine that blocks histamine H1 receptors, develop a similarly high incidence of peptic ulcers following piroxicam exposure. The protective effect of mast cells is independent of TNF, blockade of H2 receptors, or acid secretion. These data indicate a critical role for mast cells and the histamine that they produce in prevention and/or repair of piroxicam-induced gastric mucosal injury. Additional studies will be required to determine whether this represents a NSAID class effect that can be exploited to develop novel therapeutic strategies to limit the incidence of NSAID-induced side effects in humans.

Effects of etoposide alone and in combination with piroxicam on canine osteosarcoma cell lines.

Science.gov (United States)

Ong, S M; Saeki, K; Tanaka, Y; Nishimura, R; Nakagawa, T

2016-12-01

Osteosarcoma (OSA) is the most common primary bone tumour in dogs. The poor survival rate in dogs with OSA highlights the need for new therapeutic approaches. This study evaluated the cytotoxic effects of etoposide, alone and in combination with piroxicam, on canine OSA cell cultures. Etoposide alone significantly suppressed cell growth and viability, whereas etoposide in combination with piroxicam exhibited concentration dependent cytotoxicity. The anti-proliferative effect was a result of inactivity of the Cdc2-cyclin B1 complex, which correlated with an increase in the G 2 /M fraction. This subsequently activated the apoptosis cascade, as indicated by elevated apoptosis levels and up-regulation of poly (ADP-ribose) polymerase proteolytic cleavage. Down-regulation of survivin expression induced by the combination treatment may have contributed to the enhanced cytotoxicity. The results of this study suggest that further investigation of etoposide and piroxicam as a therapeutic combination for canine OSA is warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mast Cells Are Critical for Protection against Peptic Ulcers Induced by the NSAID Piroxicam

Science.gov (United States)

Hampton, Daniel D.; Hale, Laura P.

2011-01-01

Many commonly used non-steroidal anti-inflammatory drugs (NSAIDs) also cause gastrointestinal toxicity, including the development of life-threatening peptic ulcers. We report that mast cell-deficient mice have an extremely high incidence of severe peptic ulceration when exposed to the NSAID piroxicam. This enhanced ulcer susceptibility can be reversed by reconstitution with mast cells. Furthermore, wild type mice treated with diphenhydramine hydrochloride, a commonly used antihistamine that blocks histamine H1 receptors, develop a similarly high incidence of peptic ulcers following piroxicam exposure. The protective effect of mast cells is independent of TNF, blockade of H2 receptors, or acid secretion. These data indicate a critical role for mast cells and the histamine that they produce in prevention and/or repair of piroxicam-induced gastric mucosal injury. Additional studies will be required to determine whether this represents a NSAID class effect that can be exploited to develop novel therapeutic strategies to limit the incidence of NSAID-induced side effects in humans. PMID:21858200

Chemoprevention of DMH-induced rat colon carcinoma initiation by combination administration of piroxicam and C-phycocyanin.

Science.gov (United States)

Saini, Manpreet Kaur; Vaiphei, Kim; Sanyal, Sankar Nath

2012-02-01

Cancer research illustrated that combinatorial studies can provide significant improvement in safety and effectiveness over the monotherapy regimens. A combination of two drugs may restrain precancerous colon polyps, opening a new possible opportunity for chemoprevention of colon cancer. In this context, chemopreventive efficacy of a combination regimen of C-phycocyanin, a biliprotein present in Spirulina platensis, a cyanobacterium, which is a selective cycloxygenase-2 (COX-2) inhibitor and piroxicam, a traditional non-steroidal anti-inflammatory drug was considered in 1,2 dimethylhyadrazine (DMH)-induced colon carcinogenesis in rats. Western blotting, immunohistochemistry, DNA fragmentation, fluorescent staining, PGE(2) enzyme immunoassay, and carrageenan-induced paw edema test were performed along with morphological and histological analysis. DMH treatment showed a rich presence of preneoplastic lesions such as multiple plaque lesions, aberrant crypt foci, and well-characterized dysplasia. These features were reduced with piroxicam and C-phycocyanin administration. The number of apoptotic cells was featured prominently in all the groups compared with DMH. DMH treatment revealed intact high molecular weight genomic DNA with no signs of laddering/DNA fragmentation while it was noticeable significantly in control and DMH + piroxicam + C-phycocyanin. DMH group showed highest COX-2 expression and PGE(2) level in comparison with other groups. Doses of piroxicam and C-phycocyanin used in the present study were established at an anti-inflammatory range. A combination regimen of piroxicam and C-phycocyanin, rather than individually has the much greater potential for reduction of DMH-induced colon cancer development and COX-2 being the prime possible target in such chemoprevention.

The output kinetics of piroxicam from emulsion microcapsules based on high methylated pectin and lactoglobulin of whey in experiments vitro

International Nuclear Information System (INIS)

Goibova, Z.V.; Bobokalonov, D.T.; Usmanova, S.R.; Teshaev, Kh.I.; Mukhidinov, Z.K.

2015-01-01

Present article is devoted to output kinetics of piroxicam from emulsion microcapsules based on high methylated pectin and lactoglobulin of whey in experiments vitro. The dependence of piroxicam output on time at various mole ratio was studied.

Reduction of the concentration and total amount of keratan sulphate in synovial fluid from patients with osteoarthritis during treatment with piroxicam.

Science.gov (United States)

Carroll, G J; Bell, M C; Laing, B A; McCappin, S; Blumer, C; Leslie, A

1992-01-01

To study the effects of piroxicam on cartilage metabolism in vivo, a three phase (placebo/piroxicam 20 mg/day by mouth/placebo) double blind controlled trial was conducted in patients with osteoarthritis of the knee joint. Twenty one patients were recruited, 19 of whom (11 women, eight men, median age 70 years) completed the treatment schedule. The knee joint under study was aspirated to dryness at four week intervals. Treatment with piroxicam was accompanied by a decrease in the pain score, an improvement in the functional index, and an increased range of movement. Reductions in the concentration (mean (SEM) 120 (6) to 110 (8) micrograms/ml) and the total amount (1.22 (0.34) to 0.99 (0.37) mg) of keratan sulphate, but not the effusion volume (9.4 (2.5) to 8.3 (2.6) ml) were observed during treatment with piroxicam. These findings are consistent with decreased proteoglycan catabolism during treatment with piroxicam. Neither depressed synthesis nor enhanced clearance of degraded proteoglycan fragments can be excluded, however. PMID:1632658

Pharmacodynamics of piroxicam from novel solid lipid microparticles formulated with homolipids from Bos indicus.

Science.gov (United States)

Nnamani, Petra O; Attama, Anthony A; Kenechukwu, Franklin C; Ibezim, Emmanuel C; Adikwu, Michael U

2013-12-01

The dissolution of piroxicam is a limiting step in its bioavailability on account of its hydrophobicity. The objective of this research was to formulate novel solid lipid microparticles (SLMs) based on homolipids (admixtures of tallow fat (TF) and Softisan(®) 142 (SFT) templated with Phospholipon(®) 90G (P90G), a heterolipid for the delivery of piroxicam. Lipid matrices consisting of TF and SFT in ratios of 1:1, 1:2 and 2:1 were templated with the heterolipid, P90G and characterized by differential scanning calorimetry (DSC). The SLMs produced by hot homogenization technique using the matrices were characterized in terms of thermal properties, particle size, morphology, drug encapsulation efficiency, stability studies and in vitro diffusion studies. In vivo pharmacodynamic study was performed using egg albumin- induced pedal edema in rats. The results showed that addition of Softisan(®) 142 improved the drug holding capacity of the micellar solution of 2:1 mixture of TF and SFT. The in vitro diffusion of piroxicam from this SLM showed maximum release of 87.53 % and followed non-Fickian diffusion kinetic mechanism. At dose equivalence of 10 mg, piroxicamloaded SLMs showed superior in vivo anti-inflammatory properties at 3 h than Feldene(®) and the pure drug sample. This study has shown that surface-modified SLMs could confer favourable properties with respect to drug release and antiinflammatory activity on SLMs for the delivery of piroxicam, thus encouraging further development of the formulations.

Effect of Piroxicam on ART Outcome: A Pilot Study

Directory of Open Access Journals (Sweden)

Farnaz Sohrabvand

2014-11-01

Full Text Available Background: One of the most important factors affecting success rates in assisted reproductive techniques (ART besides the number of oocytes retrieved and high quality embryos derived from them is the technical aspects of embryo transfer. It seems that pretreatement with uterine relaxants can be helpful in preventing unpleasant cramps which can have an adverse effect on ART outcome. In this respect, some drugs such as prostaglandin inhibitors or sedatives have been evaluated but not confirmed yet remain controversial. This study was performed in order to assess the effect of administrating Piroxicam prior to embryo transfer on pregnancy rates in ART cycles. Materials and Methods: This pilot study was performed from August 2010 through December 2011 on 50 infertile women in ART cycles. Recombinant follicle stimulating hormone (rFSH with a long gonadotropin releasing hormone (GnRH analogue protocol were used for controlled ovarian hyperstimulation. The subjects were randomly allocated into two groups of 25 patients after obtaining written consent. Group A received a 10 mg Piroxicam capsule 30 minutes before embryo transfer and group B was the control group with no treatment. Data were analyzed by Chi-square and analysis of variance (ANOVA. Results: Pregnancy rate was 34% (n=17 totally, with 32% (n=8 in group A and 36% (n=9 in group B (p=0.75. Uterine cramps were experienced by 4 women (16% in group B, while none were reported by women in group A (p=0.037. Conclusion: It seems that Piroxicam administration 30 minutes prior to embryo transfer cannot increase pregnancy rates, but can prevent or reduce uterine cramps after the procedure.

Retrospective evaluation of doxorubicin-piroxicam combination for the treatment of transitional cell carcinoma in dogs.

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Robat, C; Burton, J; Thamm, D; Vail, D

2013-02-01

To determine whether doxorubicin-piroxicam combination is safe and has activity against transitional cell carcinoma in dogs. Data was collected retrospectively from 34 dogs from two institutions over a 6-year period. Signalment, clinical presentation, treatment specifics, adverse events, response, progression-free survival and overall survival time were evaluated. Dogs received doxorubicin every 3 weeks and daily piroxicam; 17 dogs (50%) had surgery. Clinical presentations were those typically reported for transitional cell carcinoma. Mean number of doses administered was 3·5. Of the 23 dogs with measurable disease, 14 (60·5%) had stable disease, 7 (30·5%) had progressive disease and 2 (9%) a partial response. Adverse events were generally manageable, and gastrointestinal in origin; one dog died of treatment-related complications. Overall median progression-free survival and overall survival were 103 and 168 days, respectively. Cytoreductive surgery did not result in prolongation of progression-free survival, but significantly prolonged overall survival. All dogs but one died as a result of disease progression. Doxorubicin-piroxicam combination therapy is well-tolerated in dogs with transitional cell carcinoma although progression-free survival, overall survival and biological response rates appear modest. Combination with surgery appears to offer a survival advantage; however, this may reflect tumour location and volume. Prospective studies are necessary to compare activity of combination doxorubicin-piroxicam to currently applied therapies. © 2013 British Small Animal Veterinary Association.

Sublingual piroxicam in the management of postoperative pain after surgical removal of impacted mandibular third molar.

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Mohammad, Shadab; Singh, Vibha; Wadhwani, Puneet; Tayade, Himanshu P; Rathod, Onkar K

2012-01-01

Surgical removal of impacted mandibular third molar is one of the most commonly performed procedures in oral and maxillofacial surgical practice. The role of preoperative and postoperative medications for management of postoperative complications has been extensively evaluated. To assess the therapeutic effect of a single dose of 40 mg sublingual piroxicam (study group) vs 150 mg oral diclofenac (50 mg thrice a day) (control group) in patients undergoing surgical removal of impacted mandibular third molar. A total of 100 patients with asymptomatic impacted mandibular third molars were randomized into two groups. One group received two 20-mg tablets of piroxicam once daily on the first and second postoperative days, followed by one 20-mg tablet on the third post-operative day. The other group received one tablet of diclofenac 50 mg orally thrice daily on the first, second, and third post-operative days. Repeated extraoral examinations were done for continuous assessment of swelling, trismus, and reduction in pain. Overall impression of the treating physician and the patient regarding efficacy of study drugs were recorded at the end of the study. In the piroxicam group there was >50% reduction in pain on all three days postoperatively. The incidence of swelling and trismus was found to be higher in the control group as compared to the study group. Adverse events, such as gastrointestinal (GI) disturbances, were significantly higher in the diclofenac group (11%) as compared to the piroxicam group (0%). Two sublingual piroxicam 20 mg tablets once daily has better efficacy and tolerability profile than diclofenac 50 mg one tablet thrice daily in the management of pain after surgical removal of impacted mandibular third molar.

A comparison of the effect of intramuscular diclofenac, ketorolac or piroxicam on postoperative pain following laparoscopy.

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O'Hanlon, J. J.; Beers, H.; Huss, B. K.; Milligan, K. R.

1996-01-01

Sixty patients presenting for in-patient gynaecological laparoscopic surgery were randomly allocated to receive either diclofenac 75 mg (n = 20), ketorolac 30 mg (n = 20) or piroxicam 20 mg (n = 20) as an intra-muscular injection immediately after induction of anaesthesia. Postoperative visual analogue scores over the first 24 hours, using a 10 cm scale, ranged from 3.2-0.5 in the diclofenac group, 2.7-0.85 in the ketorolac group and 2.8-0.5 in the piroxicam group. The scores did not differ significantly between the three groups (p > 0.05). Mean time (SD) to first analgesia was 27(94) minutes in the piroxicam group, 16 (30) minutes in the diclofenac group and 62 (120) minutes in the piroxicam group. Six out of twenty patients in the diclofenac group required further analgesia compared to nine out of twenty in the other two drug groups. This difference was not significant. There were no reports of increased bleeding, bronchoconstriction, bleeding from the upper gastrointestinal tract, renal impairment or pain from the intra-muscular injection site in any of the groups. The administration of a non-steroidal anti-inflammatory drug to patients presenting for laparoscopic surgery reduces postoperative pain. There were no obvious differences between the agents used. PMID:8686101

The dissolution enhancement of piroxicam in its physical mixtures and solid dispersion formulations using gluconolactone and glucosamine hydrochloride as potential carriers.

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Al-Hamidi, Hiba; Obeidat, Wasfy M; Nokhodchi, Ali

2015-01-01

The solid dispersion technique is one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs; however this is reliant on a suitable carrier and solvent being selected. The work presented explores amino sugars (d-glucosamine HCl and d-gluconolactone) as potential hydrophilic carriers to improve dissolution rate of a poorly water-soluble drug, piroxicam, from physical mixtures and solid dispersion formulations. Solid dispersions of the drug and carrier were prepared using different ratios by the conventional solvent evaporation method. Acetone was used as solvent in the preparation of solid dispersions. Physical mixtures of piroxicam and carrier were also prepared for comparison. The properties of all solid dispersions and physical mixtures were studied using a dissolution tester, Fourier transform infrared, XRD, SEM and differential scanning calorimetry. These results showed that the presence of glucosamine or gluconolactone can increase dissolution rate of piroxicam compared to pure piroxicam. Glucosamine or Gluconolactone could be used as carrier in solid dispersion formulations and physical mixtures to enhance the dissolution rate. Solid state studies showed that no significant changes occurred for piroxicam in physical mixtures and solid dispersion.

Effect of virgin olive oil versus piroxicam phonophoresis on exercise-induced anterior knee pain

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Babak Nakhostin-Roohi

2016-08-01

Full Text Available Objective: The main purpose of this study was to evaluate the effects of virgin olive oil phonophoresis on female athletes' anterior knee pain (AKP. Materials and Methods: A double blinded randomized clinical trial was conducted. Ninety-three female athletes suffering from AKP voluntarily participated in this study. Patients were randomly assigned into olive oil (n=31, piroxicam (n=31 or base gel phonophoresis (n=31 groups. At the baseline visit, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC questionnaire was filled by subjects who were then treated with olive oil, piroxicam or pure phonophoresis for 12 sessions. After 6 and 12 sessions of physiotherapy, subjects filled the questionnaire again. Main outcomes were significant improvement in pain, stiffness, physical function, and total WOMAC scores. Results: Although, there was a significant reduction in symptoms of AKP at the end of the therapy in all groups (p< 0.05, but in olive oil group, this improvement was seen after 6 sessions of treatment (p< 0.001. A significant difference between olive oil group and piroxicam and/or phonophoresis group was observed after 6 sessions of therapy (p< 0.05. Conclusion: It could be proposed that phonophoresis with virgin olive oil is as effective as piroxicam gel on lowering WOMAC scores of AKP in female athletes and also has several beneficial properties including faster effect and shorter duration of therapy. The exact mechanism of beneficial action of virgin olive oil on AKP is not clear and requires further studies.

Clinical trial of osteoarthritis jamu formula compare to piroxicam

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Danang Ardiyanto

2016-12-01

Full Text Available Latar belakang: Indonesia memiliki beberapa ramuan tradisional yang telah digunakan untuk mengurangi nyeri pada osteoarthritis (OA. Namun belum ada bukti yang kuat mengenai khasiat dan keamanan dari ramuan tradisional. Penelitian ini memberikan bukti mengenai khasiat dan keamanan dari satu ramuan tradisional. Metode: Penelitian ini menggunakan metode randomized clinical trial (RCT dengan 123 subyek (pasien selama 28 hari intervensi. Penelitian ini dilakukan pada bulan Maret – Desember 2014 oleh 30 dokter Saintifikasi Jamu di 20 provinsi. Formula jamu dibandingkan dengan piroksikam sebagai kontrol positif. Parameter yang digunakan untuk mengevaluasi khasiat formula jamu dan piroxicam adalah visual analogue score (VAS, pilot geriatric arthritis project (PGAP functional status assessment (FSA, dan Short Form (SF-36. Untuk mengevaluasi keamanan digunakan nilai serum glutamic-oxaloacetic transaminase (SGOT, serum glutamic pyruvic transaminase level (SGPT, blood urea nitrogen (BUN, dan kreatinin. Hasil: Sebanyak 123 pasien yang dibagi menjadi dua kelompok yaitu 63 subyek pada kelompok formula jamu dan 60 subyek pada kelompok piroksikam. Pemberian jamu dapat menurunkan VAS secara bermakna (p<0,05 jika dibandingkan dengan hari ke-0. Nilai FSA kelompok jamu turun secara bermakna (p=0,000 jika dibandingkan dengan nilai di awal intervensi. Formula jamu dapat memperbaiki nilai SF-36 bila dibandingkan dengan hari ke-0. Nilai ketiga parameter antara jamu formula dan piroksikam, jika dibandingkan tidak berbeda bermakna (p>0,05. Kelompok formula jamu menunjukkan nilai SGOT, SGPT, BUN, dan kreatinin dalam ambang normal. Kesimpulan: Penelitian ini menunjukkan bahwa ramuan jamu secara klinis, khasiatnya sebanding dengan piroxicam dan aman setelah intervensi selama 28 hari. Kata kunci: khasiat, keamanan, RCT, ramuan Abstract Background: Indonesian herbs have several formulas which have been used traditionally to reduce pain of osteoarthritis (OA. However, there

Comparison Efficacy of Topical Piroxicam Gel and Lidocaine with Intravenous Pethidine in Reducing Pain during ESWL

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F Mohammad Alibeigi

2011-06-01

Full Text Available Introduction & Objective: ESWL is a non-invasive method of breaking stones, using acoustic shock waves. Shock waves cause temporary deep visceral pain and discomfort in entry therefore, administration of sedatives is necessary. The purpose of this study was to compare the effect of topical lidocaine and piroxicam gel with intravenous pethidine in reducing pain during ESWL. Materials & Methods: This clinical trial study was performed on 159 patients who referred to Ayatollah Kashani Hospital in Shahrkord for ESWL in 2009. Patients were randomly divided into three-groups. For the first group, intravenous pethidine (0.5 mg/kg alone was administered. The second group received topical piroxicam, and the third group received topical lidocaine in the area of flank for half an hour before ESWL. During the operation, those patients who had unbearable pain, received another 0.5 mg/kg of pethidine. Data was collected using MC Gill questionnaires and analyzed using the SPSS software, using parametric, nonparametric methods and Dunn's Multiple Comparisons tests. Results: The mean of pain scores in the first group (pethidine was 6.2 ± 6.9 while these scores were 3.2 ± 2 .7 and 3.9 ± 3.1 for the second (piroxicam gel and third group (lidocaine gel respectively. The differences in the mean score of pain was significant in the pethidine group compared to the other groups (P <0.05. The average pethidin consumption were 24 ± 16 mg for the first group (pethidine, 10 ± 13 mg for the second group (piroxicam gel, and 5 ± 9 mg for the third group (lidocaine gel. The mean difference was significant in pethidine treated group in comparison with other two groups (P < 0.05. Conclusion: The use of topical piroxicam or lidocaine reduces pain in patients after ESWL It also reduces the need for sedative drugs.

Fast dissolving cyclodextrin complex of piroxicam in solid dispersion part I: influence of β-CD and HPβ-CD on the dissolution rate of piroxicam.

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Bouchal, F; Skiba, M; Chaffai, N; Hallouard, F; Fatmi, S; Lahiani-Skiba, M

2015-01-30

Sublingual drug delivery is an interesting route for drug having significant hepatic first-pass metabolism or requiring rapid pharmacological effect as for patients suffering from swallowing difficulties, nausea or vomiting. Sublingual absorption could however be limited by the kinetic of drug dissolution. This study evaluated influences of cyclodextrins (β-CD or HP-β-CD) and their different inclusion process (spray-drying or freeze-drying) on the drug dissolution kinetic of solid dispersions in poly(ethylene glycol) (PEG, Mw 6000Da) of piroxicam, used as poor hydrosoluble drug model. A secondary objective was to determine influences of drug dispersion process in PEG (evaporation or melting methods) on the drug dissolution kinetic of piroxicam. Piroxicam solid dispersions containing or not cyclodextrins were characterized by different scanning calorimetry (DSC), Thermogravometry analyser (TGA) and Fourier transform-infrared spectroscopy (FT-IR) spectroscopy. In vitro drug dissolution study of these solid dispersions was then performed. The results demonstrated the high potential and interest of solid dispersions of drug previously included in cyclodextrins for sublingual delivery of hydrophobic drugs. This study also showed the advantages of evaporation method on the melting ones during drug dispersion in PEG. Indeed, drug complexation with cyclodextrins as dispersion by melting prevented the presence in solid dispersions of drug in crystalline form which can represent up to 63%. Moreover, dispersion in PEG by evaporation method gave more porous drug delivery system than with melting methods. This allowed complete (limited at most at 80-90% with melting methods) and quick drug dissolution without rebound effect like with melting ones. Copyright © 2014 Elsevier B.V. All rights reserved.

The interaction of new piroxicam analogues with lipid bilayers--a calorimetric and fluorescence spectroscopic study.

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Maniewska, Jadwiga; Szczęśniak-Sięga, Berenika; Poła, Andrzej; Sroda-Pomianek, Kamila; Malinka, Wiesław; Michalak, Krystyna

2014-01-01

The purpose of the present paper was to assess the ability of new piroxicam analogues to interact with the lipid bilayers. The results of calorimetric and fluorescence spectroscopic experiments of two new synthesized analogues of piroxicam, named PR17 and PR18 on the phase behavior of phospholipid bilayers and fluorescence quenching of fluorescent probes (Laurdan and Prodan), which molecular location within membranes is known with certainty, are shown in present work. The presented results revealed that, depending on the details of chemical structure, the studied compounds penetrated the lipid bilayers.

Comparison of the efficacy and tolerance of isoxicam and piroxicam following surgery for skiing accidents

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Massart, P.; Bèzes, H.

1986-01-01

1 A 10 day double-blind study was carried out comparing isoxicam (300 mg day-1) and piroxicam (40 mg day-1 for the first two days and 20 mg day-1 for the remaining days) following surgery in patients who had sustained skiing accidents. There were 20 patients in each group. The isoxicam-treated group had a slightly greater mean pain score prior to treatment. 2 Both isoxicam and piroxicam reduced pain and nocturnal awakening at days 5 and 10, but isoxicam was significantly superior to piroxicam in producing improvement in pain (at day 5, P < 0.05) and in nocturnal awakenings (at day 10, P < 0.05). 3 Both agents facilitated rehabilitation and there was no significant difference between them in this regard. 4 All patients in both groups considered themselves `better' or `much better' on day 5 of treatment. 5 Both agents were well tolerated by most patients but one patient in each group left the trial because of abdominal pain. One patient stopped isoxicam when she was found to be pregnant. PMID:3620276

Stability studies on piroxicam encapsulated niosomes.

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Ertekin, Zehra Ceren; Bayindir, Zerrin Sezgin; Yuksel, Nilufer

2015-01-01

Drug delivery systems which yield ideal treatments are currently the center of interest for researchers. Niosomes have numerous advantages over other drug delivery systems. However, stability issue is not clear yet and is a serious drawback for niosomes. In this study, the stability of niosomes was the center of interest. Piroxicam which was chosen as the model drug was loaded to niosomes. Niosomes were prepared by thin-film method and different forms (aqueous dispersion, lyophilized powder and lyophilized powder with cryoprotectant) of the original niosome formulation were prepared. The samples were stored either at 5°C±3°C or 25°C±2°C/60% RH±5% RH for 3 months. The drug leakage percent, particle size and distribution, zeta potential, drug release profiles were determined and niosomes were visualized under optic microscope. Niosome formulation provided sustained release of piroxicam. The drug leakage from stored niosomes was observed at the level of 1.56-6.63 %. Individual vesicle images were obtained for all samples by optical microscope. However, particle size of niosomes was increased upon storage. The zeta potential values were neither related to time nor physical form. Drug release profiles and amounts were quite similar for all forms of niosomes and the original formulation but a slight decrease was noticed on drug release amounts by time. This indicates that niosomes become more rigid by time. Although the ideal storage was obtained with lyophilized niosomes at 5±3°C in this study, the usage of suitable cryoprotectant and optimized lyophilization process should be further evaluated.

Análise exploratória aplicada no estudo de medicamentos contendo piroxicam Exploratory analysis applied in study of pharmaceutical formulations with piroxicam

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Graciele Parisotto

2005-12-01

Full Text Available A identificação de diferentes formulações de medicamentos manipulados contendo piroxicam foi estudada, empregando espectros de reflexão difusa no infravermelho médio com transformada de Fourier (DRIFTS, em associação com a técnica de análise por agrupamentos hierárquicos (AAH. Os espectros de amostras, de 5 diferentes farmácias de manipulação, contendo piroxicam (10 mg e 20 mg e seus respectivos excipientes, foram adquiridos em um espectrofotômetro NICOLET Magna 550, obtendo-se duas réplicas de cada amostra. Para a análise multivariada, as informações espectrais foram tratadas no programa Pirouette® 2.7 da Infometrix, utilizando-se as regiões espectrais 1340 a 1470 cm-1, 1535 a 1680 cm-1, 2800 a 3004 cm-1 e 3290 a 3400 cm-1. Os dendogramas foram construídos com os dados auto-escalados, e correção do espalhamento da luz (MSC, utilizando três tipos de construção: simples, flexível e incremental. Com a aplicação da análise hierárquica de agrupamentos constatou-se a formação de dois grupos distintos, um contendo os princípios ativos, e outro contendo os excipientes. Os resultados demonstram que a técnica DRIFTS em conjunto com análise por agrupamentos hierárquicos constitui uma alternativa para o controle de qualidade dos processos de produção de medicamentos.The identification of different pharmaceutical formulations with piroxicam was studied, using spectra of diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS, in association with hierarchical cluster analysis (HCA technique. The spectra of samples of the 5 different compounding pharmacies, containing 10 or 20 mg of piroxicam and its respective inactive ingredients, had been collected in Nicolet Magna 550 spectrophotometer. For the multivariate analysis, the spectral information had been processed in software package Pirouette® 2.7 of the Infometrix. The dendograms had been constructed with the autoscaled data, and multiplicative scatter

Micellar dipolar rearrangement is sensitive to hydrophobic chain length: Implication for structural switchover of piroxicam.

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Sethy, Dasaratha; Chakraborty, Hirak

2016-10-01

The interfacial properties of the membrane are exceptionally vital in drug-membrane interaction. They not only select out a particular prototropic form of the drug molecule for incorporation, but are also potent enough to induce structural switchover of these drugs in several cases. In this work, we quantitatively monitored the change in dipolar rearrangement of the micellar interface (as a simplified membrane mimic) by measuring the dielectric constant and dipole potential with the micellization of SDS at pH 3.6. The dielectric constant and dipole potential were measured utilizing the fluorescence of polarity sensitive probe, pyrene and potential-sensitive probe, di-8-ANEPPS, respectively. Our study demonstrates that the change in dipolar rearrangement directly influences the switchover equilibrium between the anionic and neutral from of piroxicam. We have further extended our work to evaluate the effect of hydrophobic chain length of the surfactants on the dipolar rearrangement and its effect on the structural switchover of piroxicam. It is interesting that the extent of switchover of piroxicam is directly correlated with the dipolar rearrangement induced bythe varying hydrophobic chain length of the surfactants. To the best of our knowledge, our results constitute the first report to show the dependence of dipole potential on the hydrophobic chain length of the surfactant and demonstrate that the dipolar rearrangement directly tunes the extent of structural switchover of piroxicam, which was so far only intuitive. We consider that this new finding would have promising implication in drug distribution and drug efficacy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Quantification of piroxicam and 5'-hydroxypiroxicam in human plasma and saliva using liquid chromatography-tandem mass spectrometry following oral administration.

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Calvo, Adriana Maria; Santos, Gabriel Mulinari; Dionísio, Thiago José; Marques, Maria Paula; Brozoski, Daniel Thomas; Lanchote, Vera Lúcia; Fernandes, Maria Helena Raposo; Faria, Flávio Augusto Cardoso; Santos, Carlos Ferreira

2016-02-20

Saliva sampling used to quantify piroxicam and 5'-hydroxypiroxicam is a noninvasive and painless method when compared to sequential blood sampling. For that, a rapid, selective and sensitive liquid chromatography-tandem mass spectrometric method for simultaneous determination of piroxicam and 5'-hydroxypiroxicam in saliva and human plasma was developed and validated. Piroxicam and its major metabolite were separated using a LiChroCART 125-4 RP Select-B Sorbent C18 column using a mixture of methanol and 2% phosphoric acid (pH 2.7) (70:30, v/v) for the mobile phase with a flow injection of 1mL/min. The run time was 4min. Volunteers had saliva and blood sampled before, 1, 2, 3, 4, 5, 6, 8, 11, 24, 48 and 72h after taking a 20mg oral dose of piroxicam. The pharmacokinetic parameters of piroxicam in plasma samples were as follows: AUC0-72 (64819hng/mL), predicted clearance (0.2L/h), distribution volume (14.8L), elimination half-life (50.7h) and saliva/plasma concentration ratio (0.003). The estimation of all pharmacokinetic parameters for 5'-hydroxypiroxicam would require collections beyond 72h; however, it was possible to quantify the mean maximum concentration (133ng/mL), time to peak concentration (53.6h), mean AUC0-72 (6213hng/mL), predicted clearance (110.3L/h) and saliva/plasma concentration ratio (0.04). The developed methods proved effective and sensitive for determining the lower quantification limit of piroxicam in plasma (6.1ng/mL) and saliva (0.15ng/mL) and of 5'-hydroxypiroxicam in plasma (1.2ng/mL) and saliva (0.15ng/mL). Copyright © 2015 Elsevier B.V. All rights reserved.

Economic evaluation of the restriction in the use piroxicam in Spain.

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Maciá Martínez, Miguel-Ángel

2015-01-01

A retrospective economic evaluation was performed on the restriction of the use of piroxicam in Spain, a non-steroidal anti-inflammatory drug, with a proven higher risk of serious gastrointestinal complications compared to other non-steroidal anti-inflammatory drugs with the objective of putting the relevance of these activities into context. A retrospective cost-effectiveness analysis and a budget impact analysis were performed. Costs and cases of serious gastrointestinal complications were compared in the non-intervention (use of piroxicam) and the intervention scenarios (use of other non-steroidal anti-inflammatory drugs). The cost of serious gastrointestinal complications was obtained from the Diagnosis Related Groups and the cost of non-steroidal anti-inflammatory drugs from usage data in the Spanish national health system. The risk of serious gastrointestinal complications was obtained from epidemiological studies. The regulatory intervention was the dominant option. In that sense, 0.81 euros per treated patient were saved, 2.75 cases of serious gastrointestinal complications were avoided per 10,000 patients and 578,608 euros were saved in total in Spain in the first year following the intervention. It is possible to perform complete economical evaluations on pharmacovigilance actions. The intervention performed by the Spanish Agency for Medicines and Medical Devices, AEMPS on piroxicam not only achieved the objective of preventing adverse drug reactions but also resulted in significant economical savings even under conservative assumptions. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Kinetics of piroxicam release from low-methylated pectin/zein hydrogel microspheres

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The kinetics of a model drug (piroxicam) release from pectin/zein hydrogel microspheres was studied under conditions simulating the gastrointestinal tract. It is established that the rate-limiting step in the release mechanism is drug diffusion out of the microspheres rather than its dissolution. ...

Real-time UV imaging of piroxicam diffusion and distribution from oil solutions into gels mimicking the subcutaneous matrix.

Science.gov (United States)

Ye, Fengbin; Larsen, Susan Weng; Yaghmur, Anan; Jensen, Henrik; Larsen, Claus; Østergaard, Jesper

2012-05-12

A novel real-time UV imaging approach for non-intrusive investigation of the diffusion and partitioning phenomena occurring during piroxicam release from medium chain triglyceride (MCT) solution into two hydrogel matrices is described. Two binary polymer/buffer gel matrices, 0.5% (w/v) agarose and 25% (w/v) Pluronic F127, were applied as simple models mimicking the subcutaneous tissue. The evolution of the absorbance maps as a function of time provided detailed information on the piroxicam release processes upon the exposure of the gel matrices to MCT. Using calibration curves, the concentration maps of piroxicam in the UV imaging area were determined. Regression of the longitudinal concentration-distance profiles, which were obtained using expressions derived from Fick's second law, provided the diffusivity and the distribution coefficients of piroxicam penetrated into the gels. The obtained MCT-agarose (pH 7.4) distribution coefficient of 1.4 was identical to the MCT-aqueous (pH 7.4) distribution coefficient determined by the shake-flask method whereas that of the MCT-Pluronic F127 system was four times less. The experimental data show that UV imaging may have considerable potential for investigating the transport properties of drug formulations intended for the subcutaneous administration. Copyright © 2012 Elsevier B.V. All rights reserved.

The nonsteroidal antiinflammatory drug piroxicam reverses the onset of depressive-like behavior in 6-OHDA animal model of Parkinson's disease.

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Santiago, R M; Tonin, F S; Barbiero, J; Zaminelli, T; Boschen, S L; Andreatini, R; Da Cunha, C; Lima, M M S; Vital, M A B F

2015-08-06

Depression is one of the most common psychiatric symptoms in patients with Parkinson's disease (PD). Some authors have reported that depression is characterized by activation of the inflammatory response. Animal models of PD also present with depressive-like behavior, such as increased immobility time in the modified forced swim test and anhedonia-like behavior in the sucrose preference test. Considering the potential neuroprotective effect of nonsteroidal antiinflammatory drugs in neurodegenerative diseases, the objective of the present study was to investigate the effects of piroxicam on depressive-like behavior in male Wistar rats lesioned with 6-hydroxydopamine (6-OHDA) in the substantia nigra (SN). Antidepressant-like effects were observed after prolonged administration of piroxicam for 21days. In the forced swim test, the 6-OHDA+saline group exhibited significant reductions in swimming time and increased immobility time compared with the sham+saline. In the sucrose preference test, the 6-OHDA+piroxicam group exhibited no reduction of sucrose preference compared with the sham+saline, with significant effects of treatment and time and a significant treatment×time interaction. 5-Hydroxytryptamine (5-HT) levels significantly decreased in the hippocampus in the 6-OHDA+saline group and not changed in the 6-OHDA+piroxicam group when compared with the sham+saline on day 21. In conclusion, 21-day treatment with piroxicam reversed the onset of depressive-like behavior and prevented the reduction of hippocampal 5-HT levels. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Photoacoustic evaluation of the penetration of piroxicam gel applied with phonophoresis into human skin

International Nuclear Information System (INIS)

Silveira, F L F D; Barja, P R; Acosta-Avalos, D

2010-01-01

The photoacoustic (PA) technique has been increasingly employed in biomedical studies, allowing in vivo skin measurements not easily performed with other techniques. It is possible to use PA measurements to evaluate transdermal delivery of products topically applied through manual massage or phonophoresis, that is the utilization of ultrasound waves to enhance drug absorption. The aim of this study was to analyze the influence of the period of phonophoresis application in the transdermal penetration of piroxicam gel. In vivo PA measurements employed a tungsten lamp as light source and a thin aluminum foil closing the PA chamber. The PA signals of the arm (i) clean; and (ii) after phonophoresis were utilized to estimate the concentration of piroxicam into skin. For all (4) volunteers, drug concentration in skin after phonophoresis application was the same for the different application times employed; in this way, phonophoresis for one minute seemed to be sufficient to enhance piroxicam penetration into skin. The actual amount of drug delivered into tissue depends on the person, suggesting a dependency with the skin type, which affects the PA signal level [2]. We conclude that drug delivery depends not only on the application method, but also on the specific skin type.

Capillary electrophoresis to determine entrapment efficiency of a nanostructured lipid carrier loaded with piroxicam

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Jessica Otarola

2015-02-01

Full Text Available A simple and fast capillary electrophoresis method has been developed to determine the amount of piroxicam loaded in a drug delivery system based on nanostructured lipid carriers (NLCs. The entrapment efficiency of the nanostructured lipid carrier was estimated by measuring the concentration of drug not entrapped in a suspension of NLC. The influence of different parameters on migration times, peak symmetry, efficiency and resolution was studied; these parameters included the pH of the electrophoretic buffer solution and the applied voltage. The piroxicam peak was obtained with a satisfactory resolution. The separation was carried out using a running buffer composed of 50 mM ammonium acetate and 13.75 mM ammonia at pH 9. The optimal voltage was 20 kV and the cartridge temperature was 20 °C. The corresponding calibration curve was linear over the range of 2.7–5.4 µg/mL of NLC suspension. The reproducibility of migration time and peak area were investigated, and the obtained RSD% values (n=5 were 0.99 and 2.13, respectively. Keywords: Capillary electrophoresis, Drug delivery system, Nanostructured lipid carrier, Piroxicam

Photoacoustic evaluation of the penetration of piroxicam gel applied with phonophoresis into human skin

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Silveira, F L F D; Barja, P R [Research and Development Institute, UNIVAP, Av. Shishima Hifumi 2911, Sao Jose dos Campos, SP, 12209-010 (Brazil); Acosta-Avalos, D, E-mail: barja@univap.b [Centro Brasileiro de Pesquisas Fisicas (CBPF), R.Xavier Sigaud 150, Rio de Janeiro, RJ, 22290-180 (Brazil)

2010-03-01

The photoacoustic (PA) technique has been increasingly employed in biomedical studies, allowing in vivo skin measurements not easily performed with other techniques. It is possible to use PA measurements to evaluate transdermal delivery of products topically applied through manual massage or phonophoresis, that is the utilization of ultrasound waves to enhance drug absorption. The aim of this study was to analyze the influence of the period of phonophoresis application in the transdermal penetration of piroxicam gel. In vivo PA measurements employed a tungsten lamp as light source and a thin aluminum foil closing the PA chamber. The PA signals of the arm (i) clean; and (ii) after phonophoresis were utilized to estimate the concentration of piroxicam into skin. For all (4) volunteers, drug concentration in skin after phonophoresis application was the same for the different application times employed; in this way, phonophoresis for one minute seemed to be sufficient to enhance piroxicam penetration into skin. The actual amount of drug delivered into tissue depends on the person, suggesting a dependency with the skin type, which affects the PA signal level [2]. We conclude that drug delivery depends not only on the application method, but also on the specific skin type.

THE EFFECT OF PIROXICAM ON THE METABOLISM OF ISOLATED HUMAN CHONDROCYTES

NARCIS (Netherlands)

BULSTRA, SK; KUIJER, R; BUURMAN, WA; TERWINDTROUWENHORST, E; GUELEN, PJM; VANDERLINDEN, AJ

The effect of piroxicam on the metabolism of healthy and osteoarthrotic (OA) chondrocytes was studied in vitro. The chondrocytes were obtained from five healthy, five moderately OA, and four severely OA hips or knees. The chondrocytes were cultured in a high-density, short-term in vitro model. In

The selective and non-selective cyclooxygenase inhibitors valdecoxib and piroxicam induce the same postoperative analgesia and control of trismus and swelling after lower third molar removal

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V. Benetello

2007-08-01

Full Text Available We compared the clinical efficacy of orally administered valdecoxib and piroxicam for the prevention of pain, trismus and swelling after removal of horizontally and totally intrabony impacted lower third molars. Twenty-five patients were scheduled to undergo removal of symmetrically positioned lower third molars in two separate appointments. Valdecoxib (40 mg or piroxicam (20 mg was administered in a double-blind, randomized and crossed manner for 4 days after the surgical procedures. Objective and subjective parameters were recorded for comparison of postoperative courses. Both agents were effective for postoperative pain relief (N = 19. There was a similar mouth opening at suture removal compared with the preoperative values (86.14 ± 4.36 and 93.12 ± 3.70% of the initial measure for valdecoxib and piroxicam, respectively; ANOVA. There was no significant difference regarding the total amount of rescue medication taken by the patients treated with valdecoxib or piroxicam (173.08 ± 91.21 and 461.54 ± 199.85 mg, respectively; Wilcoxon test. There were no significant differences concerning the swelling observed on the second postoperative day compared to baseline measures (6.15 ± 1.84 and 8.46 ± 2.04 mm for valdecoxib and piroxicam, respectively; ANOVA or on the seventh postoperative day (1.69 ± 1.61 and 2.23 ± 2.09 mm for valdecoxib and piroxicam, respectively; ANOVA. The cyclooxygenase-2 selective inhibitor valdecoxib is as effective as the non-selective cyclooxygenase inhibitor piroxicam for pain, trismus and swelling control after removal of horizontally and totally intrabony impacted lower third molars.

Quantum Chemical Calculations and Molecular Docking Studies of Some NSAID Drugs (Aceclofenac, Salicylic Acid, and Piroxicam as 1PGE Inhibitors

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S. Suresh

2016-01-01

Full Text Available The molecular structure of the three compounds Aceclofenac (I, Salicylic Acid (II, and Piroxicam (III has been determined using Gaussian 03W program with B3LYP method using 6-311++G (d,p basis set calculations. The molecular structures were fully optimized with atomic numbering scheme adopted in the study. To understand the mode of binding and molecular interaction, the docking studies of compounds Aceclofenac (I, Salicylic Acid (II, and Piroxicam (III have been carried out with prostaglandin H2 synthase-1 (1PGE as target using induced fit docking. The molecular docking results show that the interactions and energy for Aceclofenac, Salicylic Acid, and Piroxicam show the best results when docked with prostaglandin H2 synthase-1 (1PGE. The hydrogen bonding interactions of compound I (Aceclofenac are prominent with Arginine moiety, those of compound II (Salicylic Acid are prominent with Tyrosine and Serine moieties, and compound III (Piroxicam shows such interaction with Tyrosine and Arginine moieties. These interactions of prostaglandin H2 synthase-1 (1PGE with substrates are responsible for governing COX-1 inhibitor potency which in turn is a direct measure of the potency of the drug.

Characterisation of enterocolitis in the piroxicam-accelerated interleukin-10 knock out mouse

DEFF Research Database (Denmark)

Holgersen, Kristine; Kvist, Peter Helding; Markholst, Helle

2014-01-01

Background: In inflammatory bowel disease a defective mucosal barrier, a dysregulated immune response and an excessive reactivity against the gut microbiota are assumed to cause a breakdown of the intestinal homeostasis and lead to chronic inflammation. Piroxicam treatment is a method for inducti...

A Survey On The Effects Of Iontophoresis Of Piroxicam Gel On Pain And Knee Muscles Strengthn Patients With Knee Osteoarthritis

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Asghar RezaSoltani

2012-04-01

Full Text Available Background and Aim: Knee osteoarthritis is the most common cause of disability in many societies. Therapeutic measures such as using anti-inflammation drugs and physiotherapy programs have been used to suppress knee pain and improve knee joint function in patients with knee osteoarthritis. The aim of this study was to compare the effects of iontophoresis of piroxicam gel, galvanic current with or without piroxicam gel on pain, functional ability and knee muscle strength in patients with knee osteoarthritis.Materials and Method: This study was a clinical trial conducted in Akhtar hospital. Forty two female patients (mean age 58.52 years old with knee osteoarthritis participated in this study. The protocol was performed in Physiotherapy Clinic of Mazandaran Medical University, Mazandaran, Iran. All patients were randomly assigned to three groups. Iontophoresis of piroxicam gel was applied for group 1 (n=14, proxicam gel for group 2 (n=14 and galvanic current for group 3 (n=14. The procedure was carried out for 20-minutes, three times a week and for two following weeks. Knee pain and functional ability were estimated by knee injury and osteoarthritis outcome score (KOOS questioner and the strength of knee extensor and flexor muscles by an isometric device just before the first treatment and immediately after the last treatment times.Results: A significant decrease in pain and a significant increase in functional ability and the strength of knee extensor muscles were resulted in all studied groups (P < 0.05. According to ANOVA test, the level of the percentage difference which was computed for KOOS and knee muscle strength before and after treatments was significantly higher in group 1 than the other two (P < 0.01.Conclusion: Pain and knee functional ability were significantly improved in patients in all three methods. But iontophoresis of piroxicam gel appeared to be more effective in relieving pain and improving knee functional abilities than the

Comparison between paracetamol, piroxicam, their combination, and placebo in postoperative pain management of upper limb orthopedic surgery (a randomized double blind clinical trial

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Gholamreza Khalili

2016-01-01

Conclusion: IV infusion of 15 mg/kg Paracetamol used as a preventive may provide effective analgesia in comparison with IM 0.4 mg/kg Piroxicam or placebo. Addition of Piroxicam to Paracetamol has not much more benefit than Paracetamol alone, in reducing pain after upper limb orthopedic surgery.

Cyclodextrin--piroxicam inclusion complexes: analyses by mass spectrometry and molecular modelling

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Gallagher, Richard T.; Ball, Christopher P.; Gatehouse, Deborah R.; Gates, Paul J.; Lobell, Mario; Derrick, Peter J.

1997-11-01

Mass spectrometry has been used to investigate the natures of non-covalent complexes formed between the anti-inflammatory drug piroxicam and [alpha]-, [beta]- and [gamma]-cyclodextrins. Energies of these complexes have been calculated by means of molecular modelling. There is a correlation between peak intensities in the mass spectra and the calculated energies.

Effects on muscle performance of NSAID treatment with piroxicam versus placebo in geriatric patients with acute infection-induced inflammation. A double blind randomized controlled trial.

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Beyer, Ingo; Bautmans, Ivan; Njemini, Rose; Demanet, Christian; Bergmann, Pierre; Mets, Tony

2011-12-30

Inflammation is the main cause of disease-associated muscle wasting. In a previous single blind study we have demonstrated improved recovery of muscle endurance following celecoxib treatment in hospitalized geriatric patients with acute infection. Here we further evaluate NSAID treatment with piroxicam in a double blind RCT and investigate the role of cytokines and heat shock proteins (Hsp) with respect to muscle performance. We hypothesized that NSAID treatment would preserve muscle performance better than antibiotic treatment alone, by reducing infection-associated inflammation and by increasing expression of cytoprotective Hsp. Consecutive admissions to the geriatric ward were screened. 30 Caucasian patients, median age 84.5 years, with acute infection-induced inflammation and serum levels of CRP > 10 mg/L were included and randomized to active treatment with 10 mg piroxicam daily or placebo. Assessment comprised general clinical and biochemical parameters, 25 cytokines in serum, intra-and extracellular Hsp27 and Hsp70, Elderly Mobility Scale (EMS) scores, grip strength (GS), fatigue resistance (FR) and lean body mass (LBM). Patients were evaluated until discharge with a maximum of 3 weeks after treatment allocation. EMS scores, FR and grip work (GW), a measure taking into account GS and FR, significantly improved with piroxicam, but not with placebo. Early decreases in IL-6 serum levels with piroxicam correlated with better muscle performance at week 2. Basal expression of Hsp27 in monocytes without heat challenge (WHC) was positively correlated with FR at baseline and significantly increased by treatment with piroxicam compared to placebo. Profound modifications in the relationships between cytokines or Hsp and changes in muscle parameters were observed in the piroxicam group. Piroxicam improves clinically relevant measures of muscle performance and mobility in geriatric patients hospitalized with acute infection-induced inflammation. Underlying mechanisms may

Crystal structure of a 2:1 piroxicam–gentisic acid co-crystal featuring neutral and zwitterionic piroxicam molecules

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Elizabeth M. Horstman

2016-12-01

Full Text Available A new 2:1 co-crystal of piroxicam and gentisic acid [systematic name: 4-hydroxy-1,1-dioxo-N-(pyridin-2-yl-2H-1λ6,2-benzothiazine-3-carboxamide–2-(4-oxido-1,1-dioxo-2H-1λ6,2-benzothiazine-3-amidopyridin-1-ium–2,5-dihydroxybenzoic acid, 2C15H13N3O4S·C7H6O4] has been synthesized using a microfluidic platform and initially identified using Raman spectroscopy. In the co-crystal, one piroxicam molecule is in its neutral form and an intramolecular O—H...O hydrogen bond is observed. The other piroxicam molecule is zwitterionic (proton transfer from the OH group to the pyridine N atom and two intramolecular N—H...O hydrogen bonds occur. The gentisic acid molecule shows whole-molecule disorder over two sets of sites in a 0.809 (2:0.191 (2 ratio. In the crystal, extensive hydrogen bonding between the components forms layers propagating in the ab plane.

Validated Method for the Determination of Piroxicam by Capillary Zone Electrophoresis and Its Application to Tablets

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Arın Gül Dal

2014-01-01

piroxicam in tablets. The separation of piroxicam was conducted in a fused-silica capillary by using 10 mM borate buffer (pH 9.0 containing 10% (v/v methanol as background electrolyte. The optimum conditions determined were 25 kV for separation voltage and 1 s for injection time. Analysis was carried out with UV detection at 204 nm. Naproxen sodium was used as an internal standard. The method was linear over the range of 0.23–28.79 µg/mL. The accuracy and precision were found to be satisfied within the acceptable limits (<2%. The LOD and LOQ were found to be 0.07 and 0.19 µg/mL, respectively. The method described here was applied to tablet dosage forms and the content of a tablet was found in the limits of USP-24 suggestions. To compare the results of capillary electrophoretic method, UV spectrophotometric method was developed and the difference between two methods was found to be insignificant. The capillary zone electrophoretic method developed in this study is rapid, simple, and suitable for routine analysis of piroxicam in pharmaceutical tablets.

Tautomeric transformations of piroxicam in solution: a combined experimental and theoretical study

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Ivanova, D; Deneva, V; Nedeltcheva, D

2015-01-01

Piroxicam tautomerism was studied in solution by using UV-Vis spectroscopy, NMR measurements and advanced chemometrics. It has been found that in ethanol and DMSO the enol-amide tautomer is present mainly as a sandwich type dimer. The addition of water leads to distortion of the aggregate...

The Effect of Piroxicam Administration before Surgical Removal of Mandibular Mesioangular Third Molar Compared with Acetaminophen.

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Refoua Y

2000-05-01

Full Text Available : 32 patients were entered in randomized double blind clinical research. The patients were"ndivided into two groups. Group A(18 patients were given a single dose of 20 mg Piroxicam one hour"npre-surgery. Group B(14 patients were received 325 mg Acetaminophen every six hours immediately"nafter surgery. The mouth opening was measured pre-surgical treatment. Pain relief was evaluated in both"ngroups lsl and 8th hour after surgery. The mouth opening was measured lsl and 7,b day after surgery. The"nresults showed that the analgesic effects of Piroxicam were higher than acetaminophen, however, the"ncomparison of trismus means revealed no significant difference.

Crystal structure of a 2:1 piroxicam–gentisic acid co-crystal featuring neutral and zwitterionic piroxicam molecules

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Horstman, Elizabeth M.; Bertke, Jeffery A.; Woods, Toby J.; Kenis, Paul J. A.

2016-11-04

A new 2:1 co-crystal of piroxicam and gentisic acid [systematic name: 4-hydroxy-1,1-dioxo-N-(pyridin-2-yl)-2H-1λ⁶,2-benzothiazine-3-carboxamide–2-(4-oxido-1,1-dioxo-2H-1λ⁶,2-benzothiazine-3-amido)pyridin-1-ium–2,5-dihydroxybenzoic acid, 2C₁₅H₁₃N₃O₄S·C₇H₆O₄] has been synthesized using a microfluidic platform and initially identified using Raman spectroscopy. In the co-crystal, one piroxicam molecule is in its neutral form and an intramolecular O—H...O hydrogen bond is observed. The other piroxicam molecule is zwitterionic (proton transfer from the OH group to the pyridine N atom) and two intramolecular N—H...O hydrogen bonds occur. The gentisic acid molecule shows whole-molecule disorder over two sets of sites in a 0.809(2):0.191(2) ratio. In the crystal, extensive hydrogen bonding between the components forms layers propagating in theabplane.

Square Wave Voltammetry: An Alternative Technique to Determinate Piroxicam Release Profiles from Nanostructured Lipid Carriers.

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Otarola, Jessica; Garrido, Mariano; Correa, N Mariano; Molina, Patricia G

2016-08-04

A new, simple, and fast electrochemical (EC) method has been developed to determine the release profile of piroxicam, a nonsteroidal anti-inflammatory drug, loaded in a drug delivery system based on nanostructured lipid carriers (NLCs). For the first time, the samples were analyzed by using square wave voltammetry, a sensitive EC technique. The piroxicam EC responses allow us to propose a model that explains the experimental results and to subsequently determine the amount of drug loaded into the NLCs formulation as a function of time. In vitro drug release studies showed prolonged drug release (up to 5 days), releasing 60 % of the incorporated drug. The proposed method is a promising and stable alternative for the study of different drug delivery systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Piroxicam derivatives THz classification

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Sterczewski, Lukasz A.; Grzelczak, Michal P.; Nowak, Kacper; Szlachetko, Bogusław; Plinska, Stanislawa; Szczesniak-Siega, Berenika; Malinka, Wieslaw; Plinski, Edward F.

2016-02-01

In this paper we report a new approach to linking the terahertz spectral shapes of drug candidates having a similar molecular structure to their chemical and physical parameters. We examined 27 newly-synthesized derivatives of a well-known nonsteroidal anti-inflammatory drug Piroxicam used for treatment of inflammatory arthritis and chemoprevention of colon cancer. The testing was carried out by means of terahertz pulsed spectroscopy (TPS). Using chemometric techniques we evaluated their spectral similarity in the terahertz range and attempted to link the position on the principal component analysis (PCA) score map to the similarity of molecular descriptors. A simplified spectral model preserved 75% and 85.1% of the variance in 2 and 3 dimensions respectively, compared to the input 1137. We have found that in 85% of the investigated samples a similarity of the physical and chemical parameters corresponds to a similarity in the terahertz spectra. The effects of data preprocessing on the generated maps are also discussed. The technique presented can support the choice of the most promising drug candidates for clinical trials in pharmacological research.

Double-blind randomized controlled trial of isoxicam vs piroxicam in elderly patients with osteoarthritis of the hip and knee

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Bellamy, N.; Buchanan, W. W.; Grace, E.

1986-01-01

1 Fifty-seven elderly patients with primary osteoarthritis of the hip and knee were entered into a double-blind, randomized, controlled parallel group trial to compare the efficacy and tolerability of isoxicam (maximum = 200 mg day-1) and piroxicam (maximum = 20 mg day-1). 2 Clinical assessments were made following a 1 week NSAID-free washout period and at biweekly intervals during the next 6 weeks of active treatment. 3 The majority of patients in both groups experienced a clinically important and statistically significant therapeutic response. 4 No statistically significant between-group differences were noted with respect to drug efficacy. 5 One patient was withdrawn from the piroxicam group because of lack of effect, but there were no such withdrawals from the isoxicam group. 6 Five patients were withdrawn from the piroxicam group because of adverse reactions compared to only one withdrawal from the isoxicam group. 7 This study indicates that isoxicam is an efficacious and well-tolerated once-daily NSAID for elderly patients with osteoarthritis. PMID:3620274

Inhibition of matrix metalloproteinase-2 and 9 by Piroxicam confer neuroprotection in cerebral ischemia: an in silico evaluation of the hypothesis.

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Mazumder, Muhammed Khairujjaman; Bhattacharya, Pallab; Borah, Anupom

2014-12-01

Matrix metalloproteinases are zinc-containing endopeptidases that are involved in extracellular matrix (ECM) remodeling cascade in many neurological disorders, including cerebral ischemia (CI). Remodeling of the ECM followed by disruption of the blood-brain barrier (BBB) is one of the major factors contributing to the ultimate neurodegeneration in CI. BBB disruption causes a cascade of pathophysiologies that trigger Anoikis-like cell death. While inhibition of MMP-2 and MMP-9 decreases the extent of neuronal damage in CI, MMP-2/9 knock-out mice have reduced infarct volume in experimental animal models of CI. Piroxicam, which is a non-steroidal anti-inflammatory drug (NSAID), has been demonstrated to be protective against aquaporin-4 and acid-sensing ion channel 1a--mediated neurodegeneration in CI. However, no report exists on the inhibitory action of Piroxicam on MMPs. We tested the hypothesis that Piroxicam, with its larger molecular size and more number of interacting pharmacophores, can inhibit MMP-2 and MMP-9. A comparative study on the inhibitory potential of Piroxicam with other reported MMP-inhibitors, viz., Aspirin, Melatonin and Doxycycline, has also been performed. Since the drug has already been reported to be neuroprotective through its inhibitory action in other pathways, it can be the drug of choice in the therapeutic management and prevention of neurodegeneration in CI. Copyright © 2014 Elsevier Ltd. All rights reserved.

A comparison between the effects of topical piroxicam and EMLA cream on fistula cannulation pain in hemodialysis patients

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Mehdi Mohseni

2015-02-01

Full Text Available Background: Patients with end-stage renal failure, consider recurrent fistula cannulation pain as the most severe stress, resulted from the treatment process, and a major concern of their life. Nurses as one of the main targets of their actions, have a duty to relieve the pain. Accordingly, this study was conducted to determine the effectiveness of two topical piroxicam and EMLA on fistula cannulation pain intensity in hemodialysis patients. Materials and Methods: This clinical trial study was conducted on 75 patients referred to dialysis ward in Khorramabad Shohada hospital in 2013. Patients were randomly divided into three groups: group A (piroxicam, group B (EMLA and group C (placebo. Data collection tools included demographic information, Visual Analogue Scale (VAS and a checklist for possible side effects of the drugs. Pain intensity during fistula cannulation was measured in the three groups on two occasions, before and after the intervention. The collected data were then analyzed using Mann-Whitney and Kruskal-Wallis tests and SPSS19 software. Results: The median pain intensity before and after the intervention in the three groups, was significantly different (p <0/001. The highest median pain intensity reduction was in the EMLA, piroxicam and placebo groups respectively. In addition, a short term side effect (blanching in 16% of the subjects was detected in EMLA group. Conclusion:The results showed that EMLA cream was more effective than piroxicam gel in reducing the pain intensity of fistula cannulation in dialysis patients. Therefore, our study recommends to use EMLA cream as an easy method with ability to work by patients, to reduction pain during fistula cannulation in hemodialysis patients.

Randomized phase III trial of piroxicam in combination with mitoxantrone or carboplatin for first-line treatment of urogenital tract transitional cell carcinoma in dogs.

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Allstadt, S D; Rodriguez, C O; Boostrom, B; Rebhun, R B; Skorupski, K A

2015-01-01

Reported response rates of transitional cell carcinoma (TCC) in dogs to piroxicam in combination with either mitoxantrone or carboplatin are similar; however, it is unknown whether either drug might provide superior duration of response. To determine if the progression-free interval (PFI) of dogs with TCC treated with mitoxantrone and piroxicam was different than that of dogs receiving carboplatin and piroxicam. The hypothesis was that the efficacy of mitoxantrone is no different from carboplatin. Fifty dogs with TCC without azotemia. Prospective open-label phase III randomized study. Either mitoxantrone or carboplatin was administered every 3 weeks concurrently with piroxicam with restaging at 6-week intervals. Twenty-four dogs received carboplatin and 26 received mitoxantrone. Response was not different between groups (P = .56). None of the dogs showed complete response. In the mitoxantrone group, there were 2 (8%) partial responses (PR) and 18 (69%) dogs with stable disease (SD). In the carboplatin group, there were 3 PR (13%) and 13 (54%) dogs with SD. The PFI was not significantly different between groups (mitoxantrone = 106 days; carboplatin = 73.5 days; P = .62; hazard ratio 0.86; 95% confidence interval 0.47-1.56). Dogs with prostatic involvement experienced a shorter survival (median, 109 days) compared to dogs with urethral, trigonal, or apically located tumors; this difference was significant (median 300, 190, and 645 days, respectively; P = .005). This study did not detect a different in outcome in dogs with TCC treated with either mitoxantrone or carboplatin in combination with piroxicam. Copyright © 2015 by the American College of Veterinary Internal Medicine.

Ibuprofen or piroxicam protects nigral neurons and delays the development of l-dopa induced dyskinesia in rats with experimental Parkinsonism: Influence on angiogenesis.

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Teema, Asmaa M; Zaitone, Sawsan A; Moustafa, Yasser M

2016-08-01

Neuroinflammation and angiogenesis have been involved in the pathogenesis of Parkinson's disease (PD). This study investigated the effect of ibuprofen or piroxicam on the motor response to l-dopa and development of dyskinesia in Parkinsonian rats focusing on the anti-angiogenic role of the two non-steroidal anti-inflammatory drugs (NSAIDs). Rats were divided into nine groups as follows: Group I: the vehicle group, Group II: rotenone group, rats were injected with nine doses of rotenone (1 mg/kg/48 h), group III&IV: rats received rotenone + ibuprofen (10 or 30 mg/kg), Group V-VI: rats received rotenone + piroxicam (1 or 3 mg/kg), Group VII: rats received rotenone + l-dopa/carbidopa (100/10 mg/kg), Group VIII-IX: rats received rotenone + l-dopa/carbidopa + ibuprofen (30 mg/kg) or piroxicam (3 mg/kg). In general, drugs were administered daily for ten weeks. Rotenone-treated rats showed motor dysfunction, lower striatal dopamine, lower staining for nigral tyrosine hydroxylase but higher level of striatal cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) compared to vehicle-treated rats (P piroxicam in combination with l-dopa preserved the effect of l-dopa at the end of week 10, delayed the development of dyskinesia and decreased striatal COX-2 and VEGF levels. In conclusion, the current study suggests that ibuprofen and piroxicam are promising candidates for neuroprotection in PD and may have utility in conjunction with l-dopa in order to ensure the longevity of its action and to delay the development of dyskinesia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of the surfactant on the availability of piroxicam as a poorly hydrosoluble drug from suppositories.

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Dal Zorro, M; Franceschinis, E; Punchina, A; Realdon, N

2012-01-01

The use of surfactants in suppository formulations has been suggested to improve availability of poorly soluble drugs. In the present study, different kinds of surfactants have been investigated to clarify the influence on piroxicam release from suppositories formulated with both lipophilic and hydrophilic bases. Two hydrophilic glucose-derivate surfactants, and a polyoxylglyceride amphiphilic surfactant, all with high HLB values, were investigated for their use in improving drug availability. The two glucose derivate surfactants reduced drug availability from both lipophilic suppositories and hydrophilic formulations, according to longer disintegration times and drug micellization. The more complex surfactant, a lauroyl macrogolglyceride, showed an increase in piroxicam availability from lipophilic suppositories at the higher tested concentrations (15% and 20%). Otherwise, when used in hydrophilic formulations, it was less effective in promoting drug release and even reduced drug availability.

Topical piroxicam in vitro release and in vivo anti-inflammatory and analgesic effects from palm oil esters-based nanocream

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Muthanna F Abdulkarim

2010-11-01

Full Text Available Muthanna F Abdulkarim1*, Ghassan Z Abdullah1*, Mallikarjun Chitneni2, Ibrahim M Salman1, Omar Z Ameer1, Mun F Yam1,3, Elrashid S Mahdi1, Munavvar A Sattar1, Mahiran Basri4, Azmin M Noor11School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia; 2School of Pharmacy and Health Sciences, International Medical University, Kuala Lumpur, Malaysia; 3Faculty of Medicine and Health Sciences, 4Faculty of Science, Universiti Putra Malaysia, Selangor, Malaysia; *The First and Second Authors have Contributed Equally to this WorkIntroduction: During recent years, there has been growing interest in use of topical vehicle systems to assist in drug permeation through the skin. Drugs of interest are usually those that are problematic when given orally, such as piroxicam, a highly effective anti-inflammatory, antipyretic, and analgesic, but with the adverse effect of causing gastrointestinal ulcers. The present study investigated the in vitro and in vivo pharmacodynamic activity of a newly synthesized palm oil esters (POEs-based nanocream containing piroxicam for topical delivery.Methods: A ratio of 25:37:38 of POEs: external phase: surfactants (Tween 80:Span 20, in a ratio 80:20, respectively was selected as the basic composition for the production of a nanocream with ideal properties. Various nanocreams were prepared using phosphate-buffered saline as the external phase at three different pH values. The abilities of these formulae to deliver piroxicam were assessed in vitro using a Franz diffusion cell fitted with a cellulose acetate membrane and full thickness rat skin. These formulae were also evaluated in vivo by comparing their anti-inflammatory and analgesic activities with those of the currently marketed gel.Results: After eight hours, nearly 100% of drug was transferred through the artificial membrane from the prepared formula F3 (phosphate-buffered saline at pH 7.4 as the external phase and the marketed gel. The steady-state flux

Topical piroxicam in vitro release and in vivo anti-inflammatory and analgesic effects from palm oil esters-based nanocream.

Science.gov (United States)

Abdulkarim, Muthanna F; Abdullah, Ghassan Z; Chitneni, Mallikarjun; Salman, Ibrahim M; Ameer, Omar Z; Yam, Mun F; Mahdi, Elrashid S; Sattar, Munavvar A; Basri, Mahiran; Noor, Azmin M

2010-11-04

During recent years, there has been growing interest in use of topical vehicle systems to assist in drug permeation through the skin. Drugs of interest are usually those that are problematic when given orally, such as piroxicam, a highly effective anti-inflammatory, anti-pyretic, and analgesic, but with the adverse effect of causing gastrointestinal ulcers. The present study investigated the in vitro and in vivo pharmacodynamic activity of a newly synthesized palm oil esters (POEs)-based nanocream containing piroxicam for topical delivery. A ratio of 25:37:38 of POEs: external phase: surfactants (Tween 80:Span 20, in a ratio 80:20), respectively was selected as the basic composition for the production of a nanocream with ideal properties. Various nanocreams were prepared using phosphate-buffered saline as the external phase at three different pH values. The abilities of these formulae to deliver piroxicam were assessed in vitro using a Franz diffusion cell fitted with a cellulose acetate membrane and full thickness rat skin. These formulae were also evaluated in vivo by comparing their anti-inflammatory and analgesic activities with those of the currently marketed gel. After eight hours, nearly 100% of drug was transferred through the artificial membrane from the prepared formula F3 (phosphate-buffered saline at pH 7.4 as the external phase) and the marketed gel. The steady-state flux through rat skin of all formulae tested was higher than that of the marketed gel. Pharmacodynamically, nanocream formula F3 exhibited the highest anti- inflammatory and analgesic effects as compared with the other formulae. The nanocream containing the newly synthesized POEs was successful for trans-dermal delivery of piroxicam.

Crystallization and disorder of the polytypic α1 and α2 polymorphs of piroxicam

DEFF Research Database (Denmark)

Upadhyay, Pratik Pankaj; Bond, Andrew

2015-01-01

Polymorphism of the active pharmaceutical ingredient piroxicam, C15H13N3O4S, is investigated with an aim to clarify the identity and crystallization conditions of the α1 and α2 polymorphs. The structures are polytypic, containing identical 2-dimensional layers, with different symmetry relationships...

Piroxicam inhibits Masitinib-induced cyclooxygenase 2 expression in oral squamous cell carcinoma cells in vitro.

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Rathore, Kusum; Alexander, Mary; Cekanova, Maria

2014-08-01

Development and characterization of animal models for human cancers is important for the improvement of diagnosis and therapy. The oral squamous cell carcinoma (OSCC) of domestic animals resembles human OSCC in many aspects; thus, cell lines derived from OSCC of cats and dogs are a valuable model for human OSCC. We characterized 1 feline OSCC (FeOSCC-Sidney) and 1 canine OSCC (K9OSCC-Abby) cell line and compared their characteristics with human OSCC cell line hSCC-25. We calculated the doubling time of the new OSCC cell lines and evaluated the expression profiles of cancer-related markers and cell-cycle proteins such as c-kit, platelet-derived growth factor receptor, vascular endothelial growth factor receptor, epidermal growth factor receptor, cyclooxygenase (COX)-1, COX-2, and p27 by immunocytochemistry and Western blot analysis. We evaluated the effects of novel receptor tyrosine kinase inhibitor (Masitinib, AB1010) and the nonsteroidal anti-inflammatory drug piroxicam on the previously mentioned OSCC cells. Interestingly, AB1010 increased expression levels of COX-2 in all tested OSCCs. Cotreatment of piroxicam with Masitinib significantly inhibited cell proliferation of OSCC as compared to either drug alone through the c-kit and AKT signaling pathways. Piroxicam inhibited Masitinib-induced COX-2 expression in all tested OSCCs. Therefore, targeting these two signaling pathways simultaneously was more efficient for inhibition of OSCCs across these species. Copyright © 2014 Mosby, Inc. All rights reserved.

Efficacy of piroxicam for postoperative pain after lower third molar surgery associated with CYP2C8*3 and CYP2C9

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Calvo AM

2017-07-01

Full Text Available Adriana Maria Calvo, Paulo Zupelari-Gonçalves, Thiago José Dionísio, Daniel Thomas Brozoski, Flávio Augusto Faria, Carlos Ferreira Santos Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, São Paulo, Brazil Objective: Nonsteroidal anti-inflammatory drugs (NSAIDs are metabolized by the cytochrome P450 enzymes (CYPs, predominantly CYP2C8 and CYP2C9. The aim of this study was to evaluate the possible association of polymorphisms in the CYP2C8*3 and CYP2C9 genes with the clinical efficacy of oral piroxicam (20 mg daily for 4 days after lower third molar surgeries with regard to postoperative pain, swelling, trismus, adverse reactions, need for rescue medication and the volunteer’s overall satisfaction. Materials and methods: For this purpose, 102 volunteers were genotyped for CYP2C8*3 and CYP2C9 polymorphisms. Briefly, genomic DNA was isolated from saliva collected from volunteers subjected to invasive lower third molar surgeries, and the preoperative, intraoperative and postoperative parameters were collected and analyzed. Results: An equal amount of piroxicam sufficiently managed postoperative pain and inflammatory symptoms, with visual analog pain scores typically <40 mm for all genotypes investigated. Furthermore, only two out of 102 volunteers heterozygous for CYP2C8*3 and CYP2C9*3 reported adverse side effects. Conclusion: In general, slow metabolizers of piroxicam, who were volunteers with mutant alleles, were indifferent from normal metabolizers with the wild-type alleles and therefore did not require specialized piroxicam doses to manage postoperative pain and inflammation. Keywords: piroxicam, lower third molar surgery, P450, CYP2C8, CYP2C9, pharmacogenetics 

Acute generalized exanthematous pustulosis induced by piroxicam: a case report.

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Cherif, Y; Jallouli, Moez; Mseddi, M; Turki, H; Bahloul, Z

2014-01-01

Acute generalized exanthematous pustulosis (AGEP) is a severe adverse cutaneous reaction characterized by an acute episode of sterile pustules over erythematous-edematous skin. The main triggering drugs are antibiotics, mainly beta-lactam and macrolides. Non-steroid anti-inflammatory drugs may rarely be responsible. We describe a case of a woman with AGEP, who presented with generalized pustulosis lesions after the use of piroxicam for renal colic. The diagnosis was confirmed by the clinical and histological correlations and the dermatosis resolved after withdrawal of the drug.

Anti-Inflammatory Oxicams as Multi-donor Ligand Systems: pH- and Solvent-Dependent Coordination Modes of Meloxicam and Piroxicam to Ru and Os.

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Aman, Farhana; Hanif, Muhammad; Kubanik, Mario; Ashraf, Adnan; Söhnel, Tilo; Jamieson, Stephen M F; Siddiqui, Waseeq Ahmad; Hartinger, Christian G

2017-04-06

The nitrogen- and sulfur-containing 1,2-benzothiazines meloxicam and piroxicam are widely used as nonsteroidal anti-inflammatory drugs. Intrigued by the presence of multiple donor atoms and therefore potentially rich coordination chemistry, we prepared a series of organometallic Ru and Os compounds with meloxicam and piroxicam featuring either as mono- or bidentate ligand systems. The choice of the solvent and the pH value was identified as the critical parameter to achieve selectively mono- or bidentate coordination. The coordination modes were confirmed experimentally by NMR spectroscopy and single crystal X-ray diffraction analysis. Using DFT calculations, it was established that complexes in which meloxicam acts as a bidentate N,O donor are energetically more favorable than coordination as O,O and S,O donor systems. Since meloxicam and piroxicam derivatives have shown anticancer activity in the past, we aimed to compare the complexes with mono- and bidentate ligands on their in vitro anticancer activity. However, stability studies revealed that only the latter complexes were stable in [D 6 ]DMSO/D 2 O (5:95) and therefore no direct comparisons could be made. The meloxicam complexes 1 and 2 showed moderate cytotoxicity, whereas the piroxicam derivatives 5 and 6 were hardly active against the utilized cell lines. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis, spectral, DFT modeling, cytotoxicity and microbial studies of novel Zr(IV), Ce(IV) and U(VI) piroxicam complexes

Science.gov (United States)

El-Shwiniy, Walaa H.; Zordok, Wael A.

2018-06-01

The Zr(IV), Ce(IV) and U(VI) piroxicam anti-inflammatory drug complexes were prepared and characterized using elemental analyses, conductance, IR, UV-Vis, magnetic moment, IHNMR and thermal analysis. The ratio of metal: Pir is found to be 1:2 in all complexes estimated by using molar ratio method. The conductance data reveal that Zr(IV) and U(VI) chelates are non-electrolytes except Ce(IV) complex is electrolyte. Infrared spectroscopic confirm that the Pir behaves as a bidentate ligand co-ordinated to the metal ions via the oxygen and nitrogen atoms of ν(Cdbnd O)carbonyl and ν(Cdbnd N)pyridyl, respectively. The kinetic parameters of thermogravimetric and its differential, such as activation energy, entropy of activation, enthalpy of activation, and Gibbs free energy evaluated using Coats-Redfern and Horowitz-Metzger equations for Pir and complexes. The geometry of the piroxicam drug in the Free State differs significantly from that in the metal complex. In the time of metal ion-drug bond formation the drug switches-on from the closed structure (equilibrium geometry) to the open one. The antimicrobial tests were assessed towards some types of bacteria and fungi. The in vitro cell cytotoxicity of the complexes in comparison with Pir against colon carcinoma (HCT-116) cell line was measured. Optimized geometrical structure of piroxicam ligand by using DFT calculations.

Immunomodulatory effect of NSAID in geriatric patients with acute infection: effects of piroxicam on chemokine/cytokine secretion patterns and levels of heat shock proteins. A double-blind randomized controlled trial. (ISRCTN58517443).

Science.gov (United States)

Beyer, Ingo; Njemini, Rose; Bautmans, Ivan; Demanet, Christian; Mets, Tony

2012-03-01

Inflammation in older persons is associated with frailty, cachexia, and disability. We hypothesized that NSAID treatment in addition to antibiotics in older patients with acute infection might rapidly reduce inflammatory cytokines and might be of therapeutic potential to improve outcomes. A double-blind controlled trial was conducted in geriatric patients admitted for acute infection. Patients were randomized to receive either 10 mg piroxicam or placebo. Patients ≥70 years with CRP levels >10 mg/L of acute infectious origin were eligible. Twenty-five cyto-/chemokines as well as heat shock proteins Hsp27 (HSPB1) and Hsp70 (HSPA1A) were measured the first 4 days and then weekly until discharge, with a maximum of 3 weeks. Thirty Caucasian patients were included (median age 84.5 years, 67% female, median CRP 87.5 mg/L). In the piroxicam group, IL-6 and IP-10/CXCL10 decreased significantly during the study period. Relationships between cytokines were disrupted in the piroxicam group: for 12 out of 20 cytokines the number of correlations between changes in serum levels was significantly lower compared to placebo. Serum Hsp70 levels decreased significantly in the piroxicam group, but not in the placebo group. Without heat challenge, intracellular levels of Hsp70 in monocytes decreased in both groups, whereas HsP27 in monocytes increased with piroxicam with a significant difference compared to placebo at 3 weeks. Piroxicam in this setting cannot be considered merely as an anti-inflammatory drug, but rather as an immunomodulator. Further studies are needed to establish whether these effects can change functional outcomes in geriatric patients.

Indirect spectrophotometric determination of piroxicam and tenoxicam through oxidation with potassium permanganate

OpenAIRE

A.S. Amin; H.A. Dessouki; K.M. Khalil

2010-01-01

Three rapid, simple, accurate and selective validated spectrophtometric methods (A, B and C) for the determination of piroxicam (PX) and tenoxicam (TX) in bulk sample and in dosage forms are described. The methods are based on the oxidation of the studied drugs by a known excess of potassium permanganate in sulfuric acid medium and subsequent determination of unreacted oxidant by reacting it with Methylene Blue (Basic Blue 9) dye (method A), Acid Red 27 (Amaranth) dye (method B) and Acid Oran...

Synergistic Effect of Carboplatin and Piroxicam on Two Bladder Cancer Cell Lines.

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Silva, Jéssica; Arantes-Rodrigues, Regina; Pinto-Leite, Rosário; Faustino-Rocha, Ana I; Fidalgo-Gonçalves, Lio; Santos, Lúcio; Oliveira, Paula A

2017-04-01

This study aimed to evaluate the in vitro efficacy of carboplatin and piroxicam, both in isolation and combined, against T24 and 5637 human urinary bladder cancer cell lines. Cell viability, drug interaction, cell morphology, cell proliferation, apoptosis and autophagy were analyzed after 72 h of drug exposure. Statistical analysis was performed and values of ppiroxicam produced a more potent antiproliferative effect when compared to single drugs. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Piroxicam Reverses Endotoxin-Induced Hypotension in Rats: Contribution of Vasoactive Eicosanoids and Nitric Oxide

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Buharalioglu, C. Kemal; Korkmaz, Belma; Cuez, Tuba; Sahan-Firat, Seyhan; Sari, Ayşe Nihal; Malik, Kafait U.; Tunctan, Bahar

2011-01-01

Nitric oxide (NO) produced by inducible NO synthase (iNOS) is responsible for endotoxin-induced vascular hyporeactivity and hypotension resulting in multiple organ failure. Endotoxic shock is also characterized by decreased expression of constitutive cyclooxygenase (COX-1), cytochrome P450 (CYP) 4A and endothelial NOS (eNOS). Our previous studies demonstrated that dual inhibition of iNOS and COX with a selective COX-2 inhibitor, NS-398, or a non-selective COX inhibitor, indomethacin, restores blood pressure presumably due to increased production of 20-hydroxyeicosatetraenoic acid (20-HETE) derived from arachidonic acid (AA) by CYP4A in endotoxaemic rats. The aim of this study was to investigate the effects of piroxicam, a preferential COX-1 inhibitor, on the endotoxin-induced changes in blood pressure, expression of COX-1, inducible COX (COX-2), CYP4A1, eNOS, iNOS and heat shock protein 90 (hsp90), and production of PGI2, PGE2, 20-HETE and NO. Injection of endotoxin (10 mg/kg, i.p.) to male Wistar rats caused a fall in blood pressure and an increase in heart rate associated with elevated renal 6-keto-PGF1α and PGE2 levels as well as an increase in COX-2 protein expression. Endotoxin also caused an elevation in systemic and renal nitrite levels associated with increased renal iNOS protein expression. In contrast, systemic and renal 20-HETE levels and renal expression of eNOS, COX-1 and CYP4A1 were decreased in endotoxaemic rats. The effects of endotoxin, except for renal COX-1 and eNOS protein expression, were prevented by piroxicam (10 mg/kg, i.p.), given 1 hr after injection of endotoxin. Endotoxin did not change renal hsp90 protein expression. These data suggest that a decrease in the expression and activity of COX-2 and iNOS associated with an increase in CYP4A1 expression and 20-HETE synthesis contributes to the effect of piroxicam to prevent the hypotension during rat endotoxaemia. PMID:21463481

Piroxicam treatment augments bone abnormalities in interleukin-10 knockout mice.

Science.gov (United States)

Holgersen, Kristine; Dobie, Ross; Farquharson, Colin; vanʼt Hof, Rob; Ahmed, Syed Faisal; Hansen, Axel Kornerup; Holm, Thomas L

2015-02-01

Osteoporosis and fractures are common complications of inflammatory bowel disease. The pathogenesis is multifactorial and has been partly attributed to intestinal inflammation. The aim of this study was to evaluate bone status and assess the association between bone loss and gut inflammation in an experimental colitis model. Colitis was induced in interleukin-10 knockout mice (PAC IL-10 k.o.) by peroral administration of piroxicam for 12 days. The degree of colitis was assessed by clinical, macroscopic, and microscopic evaluation. Trabecular and cortical bone microarchitecture of tibia were determined using micro-computed tomography. Moreover, the serum levels of bone formation and bone resorption biomarkers were measured, and inflammatory protein profiling was performed on colons. PAC IL-10 k.o. mice developed severe colitis, characterized by hyperplasia and focal transmural inflammation, which was consistent with Crohn's disease-like pathology. The gut inflammation was accompanied by a 14% and 12% reduction in trabecular thickness relative to piroxicam-treated wild type and untreated wild type mice, respectively (P < 0.001). The trabecular bone structure was also changed in PAC IL-10 k.o. mice, whereas no differences in cortical bone geometry were observed. The trabecular thickness was inversely correlated with serum levels of CTX (r = -0.93, P = 0.006). Moreover, numerous inflammatory mediators, including RANKL and osteoprotegerin, were significantly increased in the colon of PAC IL-10 k.o. mice. PAC IL-10 k.o. mice develop bone loss and changed trabecular structure, as a result of increased bone resorption. Thus, the PAC IL-10 k.o. model could be a useful experimental model in preclinical research of inflammatory bowel disease-associated bone loss.

Safety evaluation of combination toceranib phosphate (Palladia®) and piroxicam in tumour-bearing dogs (excluding mast cell tumours): a phase I dose-finding study.

Science.gov (United States)

Chon, E; McCartan, L; Kubicek, L N; Vail, D M

2012-09-01

Toceranib phosphate and piroxicam have individually demonstrated antineoplastic activity. Additionally, non-steroidal anti-inflammatory therapy is often warranted in aged cancer-bearing dogs for management of osteoarthritis comorbidity. As concurrent use may be warranted for a given individual and the adverse event (AE) profile for each can be overlapping (gastrointestinal), a phase I trial was performed in tumour-bearing (non-mast cell) dogs to establish the safety of the combination using a standard 3+3 cohort design. Five dose-escalating cohorts, up to and including approved label dosage for toceranib and standard dosage for piroxicam, were completed without observing a frequency of dose-limiting AEs necessitating cohort closure. Therefore, the combination of standard dosages of both drugs (toceranib, 3.25 mg kg(-1), every other day; piroxicam, 0.3 mg kg(-1) daily) is generally safe. Several antitumour responses were observed. As with single-agent toceranib, label-indicated treatment holidays and dose reductions (e.g. 2.5-2.75 mg kg(-1)) may occasionally be required owing to gastrointestinal events. © 2011 Blackwell Publishing Ltd.

Preparo e caracterização de micropartículas de acetobutirato de celulose e poli(3-hidroxibutirato contendo piroxicam - DOI: 10.4025/actascihealthsci.v31i1.4428 Preparation and characterization of cellulose acetate butyrate and poly(3-hydroxybutyrate microparticles containing piroxicam - DOI: 10.4025/actascihealthsci.v31i1.4428

Directory of Open Access Journals (Sweden)

Melissa Zétola

2009-05-01

Full Text Available O objetivo deste trabalho foi avaliar a influência da massa molar do acetobutirato de celulose (ABC e da adição de poli(3-hidroxibutirato [PHB] sobre a morfologia das micropartículas, a eficiência de encapsulação e os perfis de liberação do piroxicam. As micropartículas foram preparadas por meio da técnica de emulsão/evaporação do solvente O/A e caracterizadas quanto à morfologia por microscopia eletrônica de varredura. O teor de fármaco nas micropartículas foi determinado utilizando o método de espectrofotometria de absorção na região do ultravioleta; os ensaios de liberação realizados, utilizando tampão fosfato pH 6,8. As micropartículas obtidas apresentaram formas irregulares, e aquelas preparadas a partir do ABC com maior massa molar apresentaram maior tamanho. Mediante planejamento fatorial, observou-se que as variáveis analisadas (massa molar do ABC e adição de PHB não influenciaram a eficiência de encapsulação do piroxicam, mas exerceram influência sobre a quantidade inicial de piroxicam liberada a partir das micropartículas.This work aims to evaluate the influence of the cellulose acetate butyrate (CAB molar weight and the addition of poly(3-hydroxybutyrate [PHB] on microparticle morphology, encapsulation efficiency and release profile of piroxicam. The microparticles were prepared using the O/W emulsion/solvent evaporation technique and characterized according to the morphology using scanning electron microscopy. The drug content in the microparticles was determined through UV spectrophotometry and a dissolution assay was conducted using phosphate buffer pH 6.8. The obtained microparticles presented irregular shape; the ones prepared with CAB with large molar weight presented a larger size. Through a factorial design, it was observed that the analyzed variables (CAB molar weight and PHB addition did not influence the encapsulation efficiency, but did influence the initial release of piroxicam from the

Study on inclusion interaction of piroxicam with β-cyclodextrin derivatives

Science.gov (United States)

Xiliang, Guo; Yu, Yang; Guoyan, Zhao; Guomei, Zhang; Jianbin, Chao; Shaomin, Shuang

2003-12-01

The inclusion behavior of piroxicam (PX) with β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), and carboxymethyl-β-cyclodextrin (CM-β-CD) was investigated by using steady-state fluorescence and nuclear magnetic resonance (NMR) technique. The various factors affecting the inclusion process were examined in detail. The remarkable fluorescence emission enhancement upon addition of CDs suggested that cyclodextrins (CDs) were most suitable for inclusion of the uncharged species of PX. The stoichiometry of the PX-CDs inclusion complexes was 1:1, except for β-CD where a 1:2 inclusion complex was formed. The formation constants showed the strongest inclusion capacity of β-CD. NMR showed the inclusion mode of PX with CDs.

[Effect of the microencapsulation process parameters piroxicam by complex coacervation].

Science.gov (United States)

Lamoudi, L; Chaumeil, J-C; Daoud, K

2015-01-01

The gelatin-acacia system is used for the microencapsulation of piroxicam by complex coacervation. The effect of some formulation parameters and process, namely the ratio of gelatin/gum acacia, core/wall ratio, concentration of crosslinking agent and crosslinking time are studied. The microcapsules properties are evaluated. The results showed that the microcapsules have a spherical shape, a coacervation efficiency greater than 70%, an average diameter less than 250 microns, a good stability and finally, the better values are obtained for gelatin/acacia ratio (5/3), ratio core/wall (1/4), an amount of 2 mL of crosslinking agent and a crosslinking time of 60 minutes. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The piroxicam complex of copper(II), trans-[Cu(Pir)2(THF)2], and its interaction with DNA

Science.gov (United States)

Hadadzadeh, Hassan; Salimi, Mona; Weil, Matthias; Jannesari, Zahra; Darabi, Farivash; Abdi, Khatereh; Khalaji, Aliakbar Dehno; Sardari, Soroush; Ahangari, Reza

2012-08-01

The mononuclear Cu(II) complex, trans-[Cu(Pir)2(THF)2], where Pir is 4-hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (piroxicam), has been prepared and characterized by elemental analysis, spectroscopic methods (UV-Vis, IR, and 1H NMR) and single crystal X-ray structure analysis. The molecular structure of the centrosymmetric complex is made up of two monoanionic bidentate Pir ligands coordinated to the Cu(II) atom through the pyridyl N atom and the carbonyl O atom of the amide group in equatorial positions. The elongated rhombic octahedral (ERO) coordination of the CuNONOO2″ chromophore is completed by the O atoms of two THF molecules in axial positions. A strong intramolecular hydrogen bond between the amide N-H function and the enolate O atom confirms the ZZZ conformation of piroxicam. In addition, CD spectroscopy and gel electrophoresis assays have been used to investigate the interaction of the complex with DNA. The results revealed that the binding of the complex with DNA led to DNA backbone distortion.

Piroxicam inhibits NMDA receptor-mediated excitotoxicity through allosteric inhibition of the GluN2B subunit: an in silico study elucidating a novel mechanism of action of the drug.

Science.gov (United States)

Mazumder, Muhammed Khairujjaman; Borah, Anupom

2014-12-01

Hyperactivation of GluN2B subunit containing N-methyl-d-aspartate receptors (NMDARs) significantly contributes to the development of several neurodegenerative diseases through a process called excitotoxicity. NMDARs are voltage-gated Ca2+ channels which when activated lead to excessive influx of Ca2+ into neurons thereby exacerbating several calcium-dependent pathways that cause oxidative stress and apoptosis. Several drugs are presently in use to counter the NMDAR-mediated excitotoxic events among which Ifenprodil and its derivatives are GluN2B selective allosteric antagonists. Certain non-steroidal anti-inflammatory drugs (NSAIDs) have also been reported to inhibit NMDARs and the resultant pathologies. Meanwhile, Piroxicam, which is a NSAID, has been reported to be protective in cerebral ischemia-induced neurodegeneration through various pathways. Since Piroxicam has more number of interacting groups as compared to other NSAIDs and also has structural similarities with Ifenprodil, we thought it prudent that Piroxicam may inhibit NMDARs similar to Ifenprodil. By using molecular docking as a tool, we validated the hypothesis and hereby report for the first time that Piroxicam can inhibit GluN2B containing NMDARs through allosteric mode similar to the well known selective antagonist--Ifenprodil; and thus can be a therapeutic drug for the prevention of excitotoxic neurodegeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

Long-term use of a new topical formulation containing piroxicam 0.8% and sunscreen: efficacy and tolerability on actinic keratosis. A proof of concept study.

Science.gov (United States)

Babino, Graziella; Diluvio, Laura; Bianchi, Luca; Orlandi, Augusto; Di Prete, Monia; Chimenti, Sergio; Milani, Massimo; Campione, Elena

2016-08-01

Cyclooxygenase (COX) 1 and 2 enzyme up-regulation is involved in the pathogenetic process of actinic keratosis (A.K.) and non-melanoma skin cancers. Diclofenac, a non-steroidal anti-inflammatory (N.S.A.I.D.) drug, is used as topical treatment of A.K. Piroxicam is a N.S.A.I.D. characterized by a high COX-1 inhibition activity. We conducted an 18 month exploratory open-label study on A.K., to assess the efficacy and tolerability of a new topical formulation of piroxicam and sunscreen in A.K. Enrolled subjects applied a galenic formulation of piroxicam 0.8%, vehiculated in a topical product containing sun filters with high (50+) and broad spectrum (UVA) actions, twice a day for 6 months. Subjects were then followed up for additional 12 months. Thirty-eight subjects with a total of 69 A.K. lesions participated in the trial. The primary outcome was the evolution of the Actinic Keratosis Erythema Scale Atrophy (A.K.E.S.A) score assessing erythema, scale, and atrophy of a target A.K. lesion. Secondary outcomes were the percentage of treated lesions with complete (100%) or partial (≥75%) clearance and the evaluation skin tolerability. A.K.E.S.A. mean (S.D.) score at baseline was 7.5 (1.2). After 6 months of treatment, A.K.E.S.A. score decreased to 0.9 (1.1), a -88% reduction versus baseline. At the end of follow-up, A.K.E.S.A. score was 0.8 (1.2). A complete response was achieved in 38 of the 69 lesions (55%, 95% C.I.: 43% to 66%) and clearance was maintained 1 year post-treatment. A partial clearance was observed in 57 of 69 treated lesions (83%, 95% C.I.: 73% to 91%). Adverse events were limited to mild local irritation. Our experience suggests that 6 month topical piroxicam 0.8% is efficacious and well tolerated in A.K. Clinical efficacy is maintained 1 year post-treatment. The main limitation of our study is that it was an open label non-controlled trial. Future controlled trials are warranted in order to compare the efficacy and tolerability of this topical

Formulation strategy and evaluation of nanocrystal piroxicam orally disintegrating tablets manufacturing by freeze-drying.

Science.gov (United States)

Lai, Francesco; Pini, Elena; Corrias, Francesco; Perricci, Jacopo; Manconi, Maria; Fadda, Anna Maria; Sinico, Chiara

2014-06-05

Piroxicam (PRX) is a non-steroidal anti-inflammatory drug characterized by a poor water solubility and consequently by a low oral bioavailability. In this work, different nanocrystal orally disintegrating tablets (ODT) were prepared to enhance piroxicam dissolution rate and saturation solubility. PRX nanocrystals were prepared by means of high pressure homogenization technique using poloxamer 188 as stabilizer. Three different ODTs were prepared with the same nanosuspension using different excipients in order to study their effect on the PRX dissolution properties. PRX nanocrystal size and zeta potential were determined by photon correlation spectroscopy. Additional characterization of PRX nanocrystal ODT was carried out by infrared spectroscopy, X-ray powder diffractometry, differential scanning calorimetry. Dissolution study was performed in distilled water (pH 5.5) and compared with PRX coarse suspension ODT, PRX/poloxamer 188 physical mixture, bulk PRX samples and a PRX commercial ODT. All PRX nanocrystal ODT formulations showed a higher drug dissolution rate than coarse PRX ODT. PRX nanocrystal ODT prepared using gelatin or croscarmellose as excipient showed a higher PRX dissolution rate compared with the commercial formulation and ODT prepared using xanthan gum. Overall results confirmed that improved PRX dissolution rate is due to the increased surface-to-volume ratio due to the nanosized drug particle but also revealed the important role of different excipients used. Copyright © 2014 Elsevier B.V. All rights reserved.

Dynamics of excited-state intramolecular proton transfer reactions in piroxicam. Role of triplet states

Science.gov (United States)

Cho, Dae Won; Kim, Yong Hee; Yoon, Minjoong; Jeoung, Sae Chae; Kim, Dongho

1994-08-01

The picosecond time-resolved fluorescence and transient absorption behavior of piroxicam at room temperature are reported. The keto tautomer in the excited singlet state ( 1K*) formed via the fast intramolecular proton transfer (≈ 20 ps) is observed. The short-lived (7.5 ns) triplet state of keto tauomer ( 3K*) is generated from 1K * in toluene whereas it is hardly observed in ethanol. Consequently, rapid reverse proton transfer takes place from 3K * to the enol triplet state ( 3E *.

Characterisation of enterocolitis in the piroxicam-accelerated interleukin-10 knock out mouse--a model mimicking inflammatory bowel disease.

Science.gov (United States)

Holgersen, Kristine; Kvist, Peter Helding; Markholst, Helle; Hansen, Axel Kornerup; Holm, Thomas Lindebo

2014-02-01

In inflammatory bowel disease a defective mucosal barrier, a dysregulated immune response and an excessive reactivity against the gut microbiota are assumed to cause a breakdown of the intestinal homeostasis and lead to chronic inflammation. Piroxicam treatment is a method for induction of colitis in IL-10 k.o. mice, which integrates a dysfunction of both the intestinal barrier and the immune system. However, the translational value of this model has not been thoroughly clarified. To characterise the piroxicam-accelerated colitis (PAC) IL-10 k.o. model with respect to clinical features, pathogenic mechanisms and its ability to respond to existing therapies. The PAC IL-10k.o. model was established on a C57BL/6J background and the clinical manifestations, immunological mechanisms and efficacy of ampicillin and anti-IL-12/23p40 treatment were assessed. The PAC IL-10 k.o. mice developed weight loss and diarrhoea, and colonoscopy revealed a thickened granulomatous mucosa. Histological evaluation of ileum and colon showed Crohn's disease-like changes with pronounced hyperplasia and focal transmural inflammation. Ileitis was also observed in piroxicam treated wild type mice. The total number of neutrophils, monocytes and natural killer cells was elevated in the blood compared to IL-10 k.o. and wild type mice, indicating a role of the innate immune system in the pathogenesis. These findings were supported by analyses of the intestinal cytokine profile. Ampicillin and anti-IL-12/23p40 treatment significantly suppressed disease in the model. The PAC IL-10 k.o. model resembles several features of Crohn's disease and could be a useful in vivo model in preclinical research. © 2013 Elsevier B.V. All rights reserved.

Predictive validity and immune cell involvement in the pathogenesis of piroxicam-accelerated colitis in interleukin-10 knockout mice.

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Holgersen, Kristine; Kvist, Peter Helding; Hansen, Axel Kornerup; Holm, Thomas Lindebo

2014-07-01

Piroxicam administration is a method for induction of enterocolitis in interleukin-10 knockout (IL-10 k.o.) mice. The piroxicam-accelerated colitis (PAC) IL-10 k.o. model combines a dysregulated immune response against the gut microbiota with a decreased mucosal integrity. The predictive validity and pathogenic mechanisms of the model have not been thoroughly investigated. In this study, IL-10 k.o. mice received piroxicam in the chow, and model qualification was performed by examining the efficacy of prophylactic anti-IL-12/23p40 monoclonal antibody (mAb), anti-TNFα mAb, cyclosporine A (CsA) and oral prednisolone treatment. To evaluate cell involvement in the disease pathogenesis, specific cell subsets were depleted by treatment with anti-CD4 mAb, anti-CD8 mAb or clodronate-encapsulated liposomes. T cell receptor co-stimulation was blocked by CTLA4-Ig. Cytokine profiling ELISAs and calprotectin immunohistochemistry were performed on colon tissue. Treatments with anti-IL-12/23p40 mAb and CsA prevented disease in PAC IL-10 k.o. mice and reduced IFNγ, IL-17A, MPO and calprotectin levels in colon. Anti-TNFα mAb treatment caused amelioration of selected clinical parameters. No effect of prednisolone was detected. Depletion of CD8(+) cells tended to increase mortality, whereas treatment with anti-CD4 mAb or CTLA4-Ig had no significant effect on disease development. Clodronate liposome treatment induced a loss of body weight; nevertheless macrophage depletion was associated with a significant reduction in colonic pathology. In conclusion, reference drugs with known efficacy in severe inflammatory bowel disease were efficacious in the PAC IL-10 k.o. model. Our data indicate that in this model macrophages are a main driver of colitis, whereas CD4(+) cells are not. Copyright © 2014 Elsevier B.V. All rights reserved.

Photophysical studies of oxicam group of NSAIDs: piroxicam, meloxicam and tenoxicam

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Banerjee, Rona; Chakraborty, Hirak; Sarkar, Munna

2003-04-01

Oxicam group of non steroidal anti-inflammatory drugs has been chosen as a prototype molecular group that shows diverse biological functions and dynamic structural features. Photophysical studies of three drugs from this group viz., piroxicam, meloxicam and tenoxicam have been carried out in different solvents with varying polarity, H-bond character and viscosity. The spectral responses of different prototropic forms of these drugs towards varying solvent parameters have been studied, with the aim to characterize their interaction in biomimetic environment non-invasively. The nature of the lowest transition has been identified. The extinction coefficient, quantum yield and viscosity dependence on the nature of the solvents, all indicate the extreme sensitivity of these drugs to their microenvironment.

High Performance Liquid Chromatographic Method for the Determination of Piroxicam, Naproxen, Diclofenac Sodium, and Mefenamic Acid in Bulk Drug and Pharmaceutical Preparations

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Sarmad Bahjat Dikran

2018-03-01

Full Text Available A simple accurate and rapid reversed phase high performance liquid chromatographic method has been developed and validated for the determination of four nonsteroidal anti-inflammatory drugs;  Piroxicam(PX,  Naproxen(NAP,  Diclofenac sodium(DCL and Mefenamic acid(MFNC in their pure form and different commercial pharmaceutical formulation. The separation was performed on a NUCLEODUR® 100-5 C18ec (250 × 4.6 mm i.d.; particle size 5 μm column as stationary phase with a mobile phase comprising of acetonitrile: deionized water acidified with 1% acetic acid in gradient mode. The flow rate was 1.5 mL.min-1 at the temperature 35 ºC and detection was carried out at 264 nm. Separation has been completed within 8 min. The retention times of Piroxicam, Naproxen, Diclofenac sodium, and Mefenamic acid were 4.267 min, 4.785 min, 6.555 min, and 7.683 min respectively. The linearity for Piroxicam was in the range of 3–200 μg.mL-1 and for Naproxen and Mefenamic acid was in the range 1-200 μg.mL-1, while for Diclofenac sodium was in the range 1.5–200 μg.mL-1. The proposed method was successfully applied for the determination of these drugs in their pure form and different pharmaceutical preparations (tablets, capsules, and ampoule and there is no interference with additives.

Radioiodination, purification and bioevaluation of Piroxicam in comparison with Meloxicam for imaging of inflammation

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Amin, A.M.; Gouda, A.A.; El-Sheikh, R.; Seddik, U.; Hussien, H.

2009-01-01

The present study is performed to compare the electrophilic substitution radioiodination reaction of two non-steroidal anti-inflammatory drugs namely, Piroxicam (Pirox) and Meloxicam (Melox) with 125 I where both chloramine-T (CAT) and iodogen were used as oxidizing agents. The factors affecting the percent of radiochemical yields such as drug concentration, pH of the reaction mixtures, different oxidizing agents, reaction time, temperature and different organic media were studied to optimize the conditions for labeling of Pirox and Melox and to obtain high radiochemical yields. The maximum radiochemical yield of 125 I-Piroxicam ( 125 I-Pirox) was 94% using 3.7 MBq of Na 125 I, 0.4 mM of Pirox as substrate, 3.6 mM of chloramine-T (CAT) as oxidizing agent in acetone at neutral pH = 7 and at 60 deg C within 20 min where the maximum radiochemical yield of 125 I-Melox was 92% using 0.7 mM of Melox as substrate, 0.62 mM of iodogen as oxidizing agent in acetone at neutral pH = 7 and at 25 deg C within 30 min. The radiochemical yields were determined by TLC and high-pressure liquid chromatography (HPLC). Tracers showed good localization in inflamed muscle either septic or sterile. The collected data indicates that Pirox and Melox can be used as antiinflammatory imaging agents at 24 and 2 h post injection, respectively. (author)

A novel extraction technique based on carbon nanotubes reinforced hollow fiber solid/liquid microextraction for the measurement of piroxicam and diclofenac combined with high performance liquid chromatography.

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Song, Xin-Yue; Shi, Yan-Ping; Chen, Juan

2012-10-15

A novel design of carbon nanotubes reinforced hollow fiber solid/liquid phase microextraction (CNTs-HF-SLPME) was developed to determine piroxicam and diclofenac in different real water samples. Functionalized multi-walled carbon nanotubes (MWCNTs) were held in the pores of hollow fiber with sol-gel technology. The pores and lumen of carbon nanotubes reinforced hollow fiber were subsequently filled with a μL volume of organic solvent (1-octanol), and then the whole assembly was used for the extraction of the target analytes in direct immersion sampling mode. The target analytes were extracted from the sample by two extractants, one of which is organic solvent placed inside the pores and lumen of hollow fiber and the other one is CNTs held in the pores of hollow fiber. After extraction, the analytes were desorbed in acetonitrile and analyzed using high performance liquid chromatography. This novel extraction mode showed more excellent extraction performance in comparison with conventional hollow fiber liquid microextraction (without adding CNTs) and carbon nanotubes reinforced hollow fiber solid microextraction (CNTs held in the pores of hollow fiber, but no organic solvents placed inside the lumen of hollow fiber) under the respective optimum conditions. This method provided 47- and 184-fold enrichment factors for piroxicam and diclofenac, respectively, good inter-fiber repeatability and batch-to-batch reproducibility. Linearity was observed in the range of 20-960 μg L(-1) for piroxicam, and 10-2560 μg L(-1) for diclofenac, with correlation coefficients of 0.9985 and 0.9989, respectively. The limits of detection were 4.58 μg L(-1) for piroxicam and 0.40 μg L(-1) for diclofenac. Copyright © 2012 Elsevier B.V. All rights reserved.

Piroxicam and intracavitary platinum-based chemotherapy for the treatment of advanced mesothelioma in pets: preliminary observations

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Citro Gennaro

2008-05-01

Full Text Available Abstract Malignant Mesothelioma is an uncommon and very aggressive tumor that accounts for 1% of all the deaths secondary to malignancy in humans. Interestingly, this neoplasm has been occasionally described in companion animals as well. Aim of this study was the preclinical evaluation of the combination of piroxicam with platinum-based intracavitary chemotherapy in pets. Three companion animals have been treated in a three years period with this combination. Diagnosis was obtained by ultrasonographic exam of the body cavities that evidenced thickening of the mesothelium. A surgical biopsy further substantiated the diagnosis. After drainage of the malignant effusion from the affected cavity, the patients received four cycles of intracavitary CDDP at the dose of 50 mg/m2 every three weeks if dogs or four cycles of intracavitary carboplatin at the dose of 180 mg/m2 (every 3 weeks if cats, coupled with daily administration of piroxicam at the dose of 0.3 mg/kg. The therapy was able to arrest the effusion in all patients for variable remission times: one dog is still in remission after 3 years, one dog died of progressive disease after 8 months and one cat died due to progressive neoplastic growth after six months, when the patient developed a mesothelial cuirass. The combination showed remarkable efficacy at controlling the malignant effusion secondary to MM in our patients and warrants further investigations.

Piroxicam and intracavitary platinum-based chemotherapy for the treatment of advanced mesothelioma in pets: preliminary observations

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Spugnini, Enrico P; Crispi, Stefania; Scarabello, Alessandra; Caruso, Giovanni; Citro, Gennaro; Baldi, Alfonso

2008-01-01

Malignant Mesothelioma is an uncommon and very aggressive tumor that accounts for 1% of all the deaths secondary to malignancy in humans. Interestingly, this neoplasm has been occasionally described in companion animals as well. Aim of this study was the preclinical evaluation of the combination of piroxicam with platinum-based intracavitary chemotherapy in pets. Three companion animals have been treated in a three years period with this combination. Diagnosis was obtained by ultrasonographic exam of the body cavities that evidenced thickening of the mesothelium. A surgical biopsy further substantiated the diagnosis. After drainage of the malignant effusion from the affected cavity, the patients received four cycles of intracavitary CDDP at the dose of 50 mg/m2 every three weeks if dogs or four cycles of intracavitary carboplatin at the dose of 180 mg/m2 (every 3 weeks) if cats, coupled with daily administration of piroxicam at the dose of 0.3 mg/kg. The therapy was able to arrest the effusion in all patients for variable remission times: one dog is still in remission after 3 years, one dog died of progressive disease after 8 months and one cat died due to progressive neoplastic growth after six months, when the patient developed a mesothelial cuirass. The combination showed remarkable efficacy at controlling the malignant effusion secondary to MM in our patients and warrants further investigations. PMID:18577247

Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery

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Barroso A.B.

2006-01-01

Full Text Available Third molar extraction is a common procedure frequently accompanied by moderate or severe pain, and involves sufficient numbers of patients to make studies relatively easy to perform. The aim of the present study was to determine the efficacy and safety of the therapeutic combination of 10 mg piroxicam, 1 mg dexamethasone, 35 mg orphenadrine citrate, and 2.5 mg cyanocobalamin (Rheumazin® when compared with 20 mg piroxicam alone (Feldene® in mandibular third molar surgery. Eighty patients scheduled for removal of the third molar were included in this randomized and double-blind study. They received (vo Rheumazin or Feldene 30 min after tooth extraction and once daily for 4 consecutive days. Pain was determined by a visual analogue scale and by the need for escape analgesia (paracetamol. Facial swelling was evaluated with a measuring tape and adverse effects and patient satisfaction were recorded. There was no statistically significant difference in facial swelling between Rheumazin and Feldene (control group. Both drugs were equally effective in the control of pain, with Rheumazin displaying less adverse effects than Feldene. Therefore, Rheumazin appears to provide a better risk/benefit ratio in the mandibular molar surgery. Since the side effects resulting from nonsteroidal anti-inflammatory drug administration are a severe limitation to the routine use of these drugs in clinical practice, our results suggest that Rheumazin can be a good choice for third molar removal treatment.

Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery

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A.B. Barroso

Full Text Available Third molar extraction is a common procedure frequently accompanied by moderate or severe pain, and involves sufficient numbers of patients to make studies relatively easy to perform. The aim of the present study was to determine the efficacy and safety of the therapeutic combination of 10 mg piroxicam, 1 mg dexamethasone, 35 mg orphenadrine citrate, and 2.5 mg cyanocobalamin (Rheumazin® when compared with 20 mg piroxicam alone (Feldene® in mandibular third molar surgery. Eighty patients scheduled for removal of the third molar were included in this randomized and double-blind study. They received (vo Rheumazin or Feldene 30 min after tooth extraction and once daily for 4 consecutive days. Pain was determined by a visual analogue scale and by the need for escape analgesia (paracetamol. Facial swelling was evaluated with a measuring tape and adverse effects and patient satisfaction were recorded. There was no statistically significant difference in facial swelling between Rheumazin and Feldene (control group. Both drugs were equally effective in the control of pain, with Rheumazin displaying less adverse effects than Feldene. Therefore, Rheumazin appears to provide a better risk/benefit ratio in the mandibular molar surgery. Since the side effects resulting from nonsteroidal anti-inflammatory drug administration are a severe limitation to the routine use of these drugs in clinical practice, our results suggest that Rheumazin can be a good choice for third molar removal treatment.

Amorphous solid dispersions of piroxicam and Soluplus(®): Qualitative and quantitative analysis of piroxicam recrystallization during storage.

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Lust, Andres; Strachan, Clare J; Veski, Peep; Aaltonen, Jaakko; Heinämäki, Jyrki; Yliruusi, Jouko; Kogermann, Karin

2015-01-01

The conversion of active pharmaceutical ingredient (API) from amorphous to crystalline form is the primary stability issue in formulating amorphous solid dispersions (SDs). The aim of the present study was to carry out qualitative and quantitative analysis of the physical solid-state stability of the SDs of poorly water-soluble piroxicam (PRX) and polyvinyl caprolactam-polyvinyl acetate-polyethylene-glycol graft copolymer (Soluplus(®)). The SDs were prepared by a solvent evaporation method and stored for six months at 0% RH/6 °C, 0% RH/25 °C, 40% RH/25 °C and 75% RH/25 °C. Fourier transform infrared spectroscopy equipped with attenuated total reflection accessory (ATR-FTIR) and Raman spectroscopy were used for characterizing the physical solid-state changes and drug-polymer interactions. The principal component analysis (PCA) and multivariate curve resolution alternating least squares (MCR-ALS) were used for the qualitative and quantitative analysis of Raman spectra collected during storage. When stored at 0% RH/6 °C and at 0% RH/25 °C, PRX in SDs remained in an amorphous form since no recrystallization was observed by ATR-FTIR and Raman spectroscopy. Raman spectroscopy coupled with PCA and MCR-ALS and ATR-FTIR spectroscopy enabled to detect the recrystallization of amorphous PRX in the samples stored at higher humidity. Copyright © 2015 Elsevier B.V. All rights reserved.

Determination of Degradation Products of Cyclobenzaprine Hydrochloride, Lidocaine and Piroxicam in a Semi-Topical Formulation: MS-MS Confirmation of Unknown Impurities.

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Cioroiu, Bogdan Ionel; Grigoriu, Ioana Cezara; Cioroiu, Mona Elisabeta; Niculaua, Marius; Lupuleasa, Roxana; Lazar, Mihai Ioan

2016-07-01

Association of cyclobenzaprine hydrochloride, piroxicam and lidocaine in a topical formulation is one of the newest innovations in the pharmaceutical formulary field. In this study, a reversed-phase liquid chromatographic method was developed for the establishment of the impurities of cyclobenzaprine hydrochloride, lidocaine and piroxicam in the semisolid topical formulation. In this study, we not only determined 2,6-dimethylaniline, 2-pyrydilamine but also specified impurities of cyclobenzaprine hydrochloride (dibenzosuberenone, amitriptyline, carbinole, cyclobenzaprine N-oxide and anthrachinone). The target compounds were determined using a mobile phase that consisted of a mixture of phosphate buffer (0.025 M; pH 6.2)-acetonitrile-methanol (60 : 13 : 27, v/v/v). A minimum of three supplementary possible degradation products were determined. Using mass spectrometry, the unspecified impurities were identified and the use of correlation matrices permitted the association with the possible source compounds. The chromatographic conditions were qualified and validated according to ICH guideline requirements to confirm specificity, linearity, accuracy and precision. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Increased localized delivery of piroxicam by cationic nanoparticles after intra-articular injection

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Kim SR

2016-11-01

Full Text Available Sung Rae Kim,1 Myoung Jin Ho,2 Sang Hyun Kim,1 Ha Ra Cho,2 Han Sol Kim,2 Yong Seok Choi,2 Young Wook Choi,1 Myung Joo Kang2 1Division of Pharmaceutical Sciences, College of Pharmacy, Chung-Ang University, Seoul, 2College of Pharmacy, Dankook University, Cheonan, Chungnam, South Korea Abstract: Piroxicam (PRX, a potent nonsteroidal anti-inflammatory drug, is prescribed to relieve postoperative and/or chronic joint pain. However, its oral administration often results in serious gastrointestinal adverse effects including duodenal ulceration. Thus, a novel cationic nanoparticle (NP was explored to minimize the systemic exposure and increase the retention time of PRX in the joint after intra-articular (IA injection, by forming micrometer-sized electrostatic clusters with endogenous hyaluronic acid (HA in the synovial cavity. PRX-loaded NPs consisting of poly(lactic-co-glycolic acid, Eudragit RL, and polyvinyl alcohol were constructed with the following characteristics: particle size of 220 nm, zeta potential of 11.5 mV in phosphate-buffered saline, and loading amount of 4.0% (w/w of PRX. In optical and hyperspectral observations, the cationic NPs formed more than 50 µm-sized aggregates with HA, which was larger than the intercellular gaps between synoviocytes. In an in vivo pharmacokinetic study in rats, area under the plasma concentration–time curve (AUC0–24 h and maximum plasma concentration (Cmax of PRX after IA injection of the cationic NPs were <70% (P<0.05 and 60% (P<0.05, respectively, compared to those obtained from drug solution. Moreover, the drug concentration in joint tissue 24 h after dosing with the cationic NPs was 3.2-fold (P<0.05 and 1.8-fold (P<0.05 higher than that from drug solution and neutrally charged NPs, respectively. Therefore, we recommend the IA cationic NP therapy as an effective alternative to traditional oral therapy with PRX, as it increases drug retention selectively in the joint. Keywords: piroxicam

Randomized double blinded placebo controlled trial comparing diclofenac and piroxicam in management of acute renal colic and its clinical implications.

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KandaSwamy, Gokul Vignesh; Dhanasekaran, Ananda Kumar; Elangovan, Aravindhan; John, Bobby; Viswaroop, Bobby; Vedanayagam, Kandasami Sangam

2015-04-29

To compare the efficacy of sublingual piroxicam 40 mg with intramuscular diclofenac 75 mg in treatment of acute renal colic. The secondary objective was to look for factors that can affect the severity of the pain and pain relief in acute renal colic. One hundred patients with acute renal colic were randomized into two groups. Group A (n = 50) received intramuscular diclofenac and sublingual methylcobalamin. Group B (n = 50) received sublingual piroxicam 40 mg and intramuscular distilled water. Pain severity was measured using Visual Analog Scale (VAS) and verbal and facial response scales. They were followed up for 3 h. Intramuscular injection of pentazocine 30 mg with promethazine 25 mg were used as rescue drugs. Both groups were comparable for age, sex distribution, body mass index (BMI), and pain duration before presentation. Significant pain relief was noticed in both groups. Sixteen percent in group A and 18% in group B had complete pain relief within 30 min (P = .75). Fifteen patients in group A and 13 patients in group B needed rescue drugs, 84% of group A and 76% of group B had complete pain relief at the end of 3 hours (P = .25). Decrease in pain by each scoring method was also comparable (P = .75). In multiple regression analysis, increasing age, positively affects the severity of pain and pain relief while increasing BMI negatively affect the initial pain relief. Acute renal colic seems to affect men more commonly than women, 81% of the study population were men. Patients with low initial pain score did not require any additional pain relief. Average pain duration before presenting to hospital is 260 min. Sixty percent of renal colics are due to stones below pelvic brim. The results show that sublingual piroxicam is as effective as intramuscular diclofenac. It can be easily self-administered and it overcomes the morbidity and time delay in getting intramuscular diclofenac.

Systematic Development of Transethosomal Gel System of Piroxicam: Formulation Optimization, In Vitro Evaluation, and Ex Vivo Assessment.

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Garg, Varun; Singh, Harmanpreet; Bhatia, Amit; Raza, Kaisar; Singh, Sachin Kumar; Singh, Bhupinder; Beg, Sarwar

2017-01-01

Piroxicam is used in the treatment of rheumatoid arthritis, osteoarthritis, and other inflammatory diseases. Upon oral administration, it is reported to cause ulcerative colitis, gastrointestinal irritation, edema and peptic ulcer. Hence, an alternative delivery system has been designed in the form of transethosome. The present study describes the preparation, optimization, characterization, and ex vivo study of piroxicam-loaded transethosomal gel using the central composite design. On the basis of the prescreening study, the concentration of lipids and ethanol was kept in the range of 2-4% w/v and 0-40% v/v, respectively. Formulation was optimized by measuring drug retention in the skin, drug permeation, entrapment efficiency, and vesicle size. Optimized formulation was incorporated in hydrogel and compared with other analogous vesicular (liposomes, ethosomes, and transfersomes) gels for the aforementioned responses. Among the various lipids used, soya phosphatidylcholine (SPL 70) and ethanol in various percentages were found to affect drug retention in the skin, drug permeation, vesicle size, and entrapment efficiency. The optimized batch of transethosome has shown 392.730 μg cm -2 drug retention in the skin, 44.312 μg cm -2  h -1 drug permeation, 68.434% entrapment efficiency, and 655.369 nm vesicle size, respectively. It was observed that the developed transethosomes were found superior in all the responses as compared to other vesicular formulations with improved stability and highest elasticity. Similar observations were noted with its gel formulation.

Evaluation of the effect of indomethacin and piroxicam administration before embryo transfer on pregnancy rate.

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Kumbasar, Serkan; Gül, Özer; Şık, Aytek

2017-03-01

The aim of this study was to evaluate the effect of non-steroidal anti-inflammatory drug (NSAID) administration before embryo transfer (ET) on pregnancy rates in women undergoing in vitro fertilization/intracytoplasmic sperm injection ET. Our study included 255 patients diagnosed with primary or secondary infertility caused by a male or tubal-related factor, endometriosis or unexplained factors. The patients were divided randomly into three groups. Two groups were administered oral piroxicam (10 mg capsules) or 100 mg indomethacin (rectal suppository), respectively, 1-2 h before ET. As a control, the third group did not receive any form of treatment before ET. Basal levels of follicle-stimulating hormone, luteinizing hormone, and level 17β-estradiol on the day of human chorionic gonadotropin administration, the collected and transferred number of embryos, and the number of grade A embryos obtained were determined in all patients. The implantation, clinical pregnancy, and miscarriage rates of the groups were compared. The clinical pregnancy rate per ET and the implantation rate were 35.2% and 12.15% in the piroxicam group, 31.7% and 10.9% in the indomethacin group, and 32.9% and 12.5% in the control, respectively. The miscarriage rates of groups 1, 2 and 3 were 12%, 11.7% and 11.7%, respectively (P = 0.964). The differences in clinical pregnancy rates among the groups were not statistically significant (P = 0.887). There were also no significant differences in the implantation rates (P = 0.842). These results suggest that NSAID administration before ET has no additional effect on pregnancy outcome in patients undergoing in vitro fertilization. © 2017 Japan Society of Obstetrics and Gynecology.

Vibrational spectra (FT-IR, FT-Raman), frontier molecular orbital, first hyperpolarizability, NBO analysis and thermodynamics properties of Piroxicam by HF and DFT methods

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Suresh, S.; Gunasekaran, S.; Srinivasan, S.

2015-03-01

The solid phase FT-IR and FT-Raman spectra of 4-Hydroxy-2-methyl-N-(2-pyridinyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (Piroxicam) have been recorded in the region 4000-400 and 4000-100 cm-1 respectively. The molecular geometry, harmonic vibrational frequencies and bonding features of piroxicam in the ground state have been calculated by Hartree-Fock (HF) and density functional theory (DFT) methods using 6-311++G(d,p) basis set. The calculated harmonic vibrational frequencies are scaled and they are compared with experimental obtained by FT-IR and FT-Raman spectra. A detailed interpretation of the vibrational spectra of the title compound has been made on the basis of the calculated potential energy distribution (PED). The electronic properties, such as HOMO and LUMO energies, molecular electrostatic potential (MESP) are also performed. The linear polarizability (α) and the first order hyper polarizability (β) values of the title compound have been computed. The molecular stability arising from hyper conjugative interaction, charge delocalization has been analyzed using natural bond orbital (NBO) analysis.

Evaluation and enhancement of physical stability of semi-solid dispersions containing piroxicam into hard gelatin capsules.

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Karataş, Ayşegül; Bekmezci, Serife

2013-01-01

The aim of the study was to investigate the physical stability of the semi-solid dispersions into the hard gelatine capsules prepared with Gelucire 44/14, Labrasol and different additives such as microcrystalline cellulose (MCC), mannitol and lactose (alpha-monohydrate) used for enhancing the stability of the formulations. The master dispersion prepared with only Gelucire 44/14 (20% w/w) and Labrasol (80% w/w) was stored in a refrigerator (5 +/- 3 degrees C), while the modified dispersions with the additives (2% w/w) were kept in a climatic chamber (25 +/- 2 degrees C / 60 +/- 5% RH) for 12 months. Dissolution tests of the semi-solid dispersions were performed in media with different pH's immediatly after preparation and after 3, 6 and 12 months of storage. FTIR and DSC studies were also carried out at the same time points. The ideal storage condition for the master dispersion was found to be at 5 degrees C. The addition of MCC, mannitol and lactose (alpha-monohydrate) to the original dispersion afforded a solidification effect on the formulation at room temperature and showed the same dissolution behavior (not less than 85% of piroxicam within 30 min in pH 1.2, 4.5 and 6.8; and water) with the master. The dispersion including lactose was stable at 25 degrees C for 12 months. However, the ideal period of storage for the modified dispersions including MCC and mannitol was 6 months at 25 degrees C. FTIR and DSC results both confirmed the amorphous state of piroxicam in all semi-solid dispersions under storage conditions for 12 months.

Desarrollo y optimización de una jalea de piroxicam 0,5 %

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Oscar García Pulpeiro

Full Text Available Se desarrolló por primera vez en Cuba, una formulación de jalea de piroxicam al 0,5 %. Se tomó como referencia la composición de la formulación líder del mercado FELDENE GELâ, a la cual se le efectuaron algunas modificaciones. Se realizaron 4 experimentos en las evaluaciones preliminares que sirvieron de base para la etapa posterior de diseño y optimización de la formulación. Se aplicó un diseño de experimentos con mezcla, para lo cual se emplearon como variables independientes la concentración de Carbopol 940, trietanolamina y hidroxipropilmetilcelulosa. Se evaluó la influencia de estos componentes en el pH, el área de extensibilidad y en algunas propiedades organolépticas. A partir de estos resultados, se seleccionó una formulación óptima.

Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study.

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Cheryl A London

Full Text Available We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI and overall survival (OS in dogs with appendicular osteosarcoma (OSA following amputation and carboplatin chemotherapy.This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126 received carboplatin chemotherapy (4 doses following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8 were removed from the study for therapy-associated adverse events compared to control dogs (n = 1. The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274; the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08. The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib.The addition of toceranib to metronomic

Impact of Toceranib/Piroxicam/Cyclophosphamide Maintenance Therapy on Outcome of Dogs with Appendicular Osteosarcoma following Amputation and Carboplatin Chemotherapy: A Multi-Institutional Study.

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London, Cheryl A; Gardner, Heather L; Mathie, Tamra; Stingle, Nicole; Portela, Roberta; Pennell, Michael L; Clifford, Craig A; Rosenberg, Mona P; Vail, David M; Williams, Laurel E; Cronin, Kim L; Wilson-Robles, Heather; Borgatti, Antonella; Henry, Carolyn J; Bailey, Dennis B; Locke, Jennifer; Northrup, Nicole C; Crawford-Jakubiak, Martin; Gill, Virginia L; Klein, Mary K; Ruslander, David M; Thamm, Doug H; Phillips, Brenda; Post, Gerald

2015-01-01

We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI) and overall survival (OS) in dogs with appendicular osteosarcoma (OSA) following amputation and carboplatin chemotherapy. This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126) received carboplatin chemotherapy (4 doses) following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each) after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control) developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control) received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control) developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8) were removed from the study for therapy-associated adverse events compared to control dogs (n = 1). The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274); the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08). The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib. The addition of toceranib to metronomic piroxicam

Femtosecond dynamics of a non-steroidal anti-inflammatory drug (piroxicam) in solution: The involvement of twisting motion

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Gil, Michał; Douhal, Abderrazzak

2008-06-01

In this contribution, we report on fast and ultrafast dynamics of a non-steroidal anti-inflammatory drug, piroxicam (PX), in methyl acetate (MAC) and triacetin (TAC), two solvents of different viscosities. The enol form of PX undergoes a femtosecond (shorter than 100 fs) electronically excited state intramolecular proton-transfer reaction to produce keto tautomers. These structures exhibit an internal twisting motion to generate keto rotamers in ˜2-5 ps, a time being longer in TAC. The transient absorption/emission spectrum is very broad indicating that the potential-energy surface at the electronically excited state is very flat, and reflecting the involvement of several coordinates along which the wavepacket of the fs-produced structures evolve.

Determination of piroxicam in pharmaceutical preparations by ultraviolet direct spectrophotometry, ultraviolet difference spectrophotometry and high performance liquid chromatography

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Hackmann, E.R.M.; Santos Gianotto, E.A. dos; Miritello Santoro, M.I.R. (Universidade de Sao Paulo (Brazil))

1993-02-01

Piroxicam in pharmaceutical preparations (capsules (C), tablets (T), oral drops (OD), suppositories (S) and simulated sample (SS)) was determined by UV direct spectrophotometry (UVS) at 333 nm, by UV difference spectrophotometry (UVDS) at 327 nm, and in C and T, by high performance liquid chromatography (HPLC). For UVS, Beer's law was obeyed in the range 3.0-8.5 [mu]g/mL. The coefficient of correlation (CC), absolute precision (AP) and relative precision (RP) were 0.9999, 0.02 and 0.33%, respectively. The coefficient of variation (CV) for C, T, OD, S and SS were 0.48%, 0.35%, 0.48% and 0.19%, respectively. The recovery average (RA) was 100.22%. For UVDS, Beer's law was obeyed in the range 5.0-15.0 [mu]g/mL. The CC, AP and RP were respectively 0.9999, 0.05 and 0.47%. The CV for C, T, OD, S and SS were 0.64%, 0.84%, 0.62%, 0.54% and 0.15%, respectively. The RA was 99.02%. In HPLC determination, a LiChrospher[reg sign] 100 RP-18 (5 [mu]m) in LiChroCART[reg sign] 125-4 column at ambient temperature with a mobile phase consisting of methanol: (buffer solution citric acid-dibasic sodium phosphate pH 3.0) (55:45) and UV detection at 254 nm enabled the determination of piroxicam in C and T. The response peak area versus concentration presented linearity in the range 10.0-100.0 [mu]g/mL. The CC, AP and RP were 0.9997, 0.45 and 0.90%, respectively. The CV was 0.51%-0.82% and the RA, 97.13%. 14 refs., 1 fig., 5 tabs.

A theoretical and spectroscopic study of conformational structures of piroxicam

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Souza, Kely Ferreira de; Martins, José A.; Pessine, Francisco B. T.; Custodio, Rogério

2010-02-01

Piroxicam (PRX) has been widely studied in an attempt to elucidate the causes and mechanisms of its side effects, mainly the photo-toxicity. In this paper fluorescence spectra in non-protic solvents and different polarities were carried out along with theoretical calculations. Preliminary potential surfaces of the keto and enol forms were obtained at AM1 level of theory providing the most stable conformers, which had their structure re-optimized through the B3LYP/CEP-31G(d,p) method. From the optimized structures, the electronic spectra were calculated using the TD-DFT method in vacuum and including the solvent effect through the PCM method and a single water molecule near PRX. A new potential surface was constructed to the enol tautomer at DFT level and the most stable conformers were submitted to the QST2 calculations. The experimental data showed that in apolar media, the solution fluorescence is raised. Based on conformational analysis for the two tautomers, keto and enol, the results indicated that the PRX-enol is the main tautomer related to the drug fluorescence, which is reinforced by the spectra results, as well as the interconvertion barrier obtained from the QST2 calculations. The results suggest that the PRX one of the enol conformers presents great possibility of involvement in the photo-toxicity mechanisms.

Mechanical Anisotropy and Pressure Induced Structural Changes in Piroxicam Crystals Probed by In Situ Indentation and Raman Spectroscopy

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Manimunda, Praveena; Hintsala, Eric; Asif, Syed; Mishra, Manish Kumar

2017-01-01

The ability to correlate mechanical and chemical characterization techniques in real time is both lacking and powerful tool for gaining insights into material behavior. This is demonstrated through use of a novel nanoindentation device equipped with Raman spectroscopy to explore the deformation-induced structural changes in piroxicam crystals. Mechanical anisotropy was observed in two major faces ( 0bar{1}1 ) and (011), which are correlated to changes in the interlayer interaction from in situ Raman spectra recorded during indentation. The results of this study demonstrate the considerable potential of an in situ Raman nanoindentation instrument for studying a variety of topics, including stress-induced phase transformation mechanisms, mechanochemistry, and solid state reactivity under mechanical forces that occur in molecular and pharmaceutical solids.

Ultrasound combined transcutaneous electrical nerve stimulation (UltraTENS) versus phonophoresis of piroxicam (PhP) in symptomatic knee osteoarthritis: A randomized double-blind, controlled trial.

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Boonhong, Jariya; Suntornpiyapan, Phitsanu; Piriyajarukul, Apatchanee

2018-02-02

Ultrasound combined with transcutaneous electrical nerve stimulation (UltraTENS) and phonophoresis of piroxicam (PhP) are combined modality therapy that frequently used in musculoskeletal pain including knee osteoarthritis (OA). But it is lack of a good clinical trial to prove and compare their effects. To compare the effects of UltraTENS with PhP on mild to moderate degree of symptomatic knee OA. Sixty-one patients (55 women), mean age of 63.4 ± 8.1 y, 50-90 mm VAS of knee pain and Kellgren-Lawrence score of grade I-III were randomly allocated into UltraTENS and PhP (N = 31 and 30, respectively). The UltraTENS group received a combined ultrasound with TENS program and a non-drug gel, whereas the PhP group got an ultrasound program with piroxicam gel and sham TENS. All patients were treated for a total of 10 sessions, consisting of five times per week and 10 min per session. Before and after treatment, patients were evaluated knee pain by using the 100-mm VAS and functional performance by Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index. The UltraTENS and PhP groups experienced considerable improvement in both VAS and total WOMAC scores post-treatment (PPhP had better VAS of pain and WOMAC scores but no statistical significance. Results show that UltraTENS and PhP were effective for relieving pain and improve functionality knee OA without significant differences between their effects.

Treatment of Multiple Actinic Keratosis and Field of Cancerization with Topical Piroxicam 0.8% and Sunscreen 50+ in Organ Transplant Recipients: A Series of 10 Cases

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Virginia Garofalo

2017-10-01

Full Text Available Organ transplant recipient (OTR subjects are at high risk of skin cancer such as squamous cell carcinoma and basal cell carcinoma. Actinic keratosis (AK is considered the precursor of these non-melanoma skin cancers. Sun protection is mandatory in subjects with AK and this preventive strategy is very important in OTR. Treatment of the field of cancerization is also crucial to reduce the risk of recurrence of skin lesions in AK and non-melanoma skin cancer patients. Activation of cyclooxygenase 1 and 2 enzymes plays an important role in the pathogenesis of skin cancers. Topical application of cyclooxygenase inhibitors such as diclofenac and, more recently, piroxicam has shown to reduce AK lesions in immunocompetent subjects. A medical device containing piroxicam and SPF 50+ sunscreen filters (P+SS has been demonstrated to be effective in reducing AK lesions and improving the field of cancerization. We report the effect of P+SS, applied for 16 weeks, in a case series of 10 OTR subjects with multiple AK lesions. P+SS treatment was associated with a relevant AK lesion reduction (>75% in 7 patients (with a complete clearance in 3 subjects with an improvement in the field of cancerization. This medical device could be considered a promising long-term curative and preventive treatment in OTR patients at high risk of non-melanoma skin cancers.

Determination of piroxicam in pharmaceutical formulations and urine samples using europium-sensitized luminescence

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Al-Kindy, Salma M.Z. [Department of Chemistry, College of Science, P.O. Box 36, Al-Khod 123, Sultan Qaboos University (Oman)], E-mail: alkindy@squ.edu.om; Suliman, Fakhr Eldin O.; Al-Wishahi, Aisha A.; Al-Lawati, Haidar A.J.; Aoudia, Muhammed [Department of Chemistry, College of Science, P.O. Box 36, Al-Khod 123, Sultan Qaboos University (Oman)

2007-12-15

A simple, selective and sensitive luminescence method for the assay of piroxicam (PX) in aqueous solution is developed. The method is based on the luminescence sensitization of europium (Eu{sup 3+}) by formation of ternary complex with PX in the presence of TOPO and Tween-80 as surfactant. The signal for Eu-PX-TOPO is monitored at {lambda}{sub ex}=359 nm and {lambda}{sub em}=615 nm. Optimum conditions for the formation of the complex in sequential injection analysis (SIA) were 0.01 M Tris buffer, pH 7.5, TOPO 5.0x10{sup -5} M, Tween-80 0.15% and 1.5 mM of Eu{sup 3+}, which allows the determination of 100-1000 ppb of PX with limit of detection (LOD) of 29 ppb. The relative standard deviations of the method range between 0.5% and 3.9% indicating excellent reproducibility of the method. The proposed method was successfully applied for the assay of PX in pharmaceutical formulations and in urine samples. Average recoveries of 100.8{+-}1.7% was obtained in tablet, whereas a recovery of 97.5{+-}2.0% was obtained for the total PX (PX+hydoxy-PX) in urine sample.

Determination of piroxicam in pharmaceutical formulations and urine samples using europium-sensitized luminescence

International Nuclear Information System (INIS)

Al-Kindy, Salma M.Z.; Suliman, Fakhr Eldin O.; Al-Wishahi, Aisha A.; Al-Lawati, Haidar A.J.; Aoudia, Muhammed

2007-01-01

A simple, selective and sensitive luminescence method for the assay of piroxicam (PX) in aqueous solution is developed. The method is based on the luminescence sensitization of europium (Eu 3+ ) by formation of ternary complex with PX in the presence of TOPO and Tween-80 as surfactant. The signal for Eu-PX-TOPO is monitored at λ ex =359 nm and λ em =615 nm. Optimum conditions for the formation of the complex in sequential injection analysis (SIA) were 0.01 M Tris buffer, pH 7.5, TOPO 5.0x10 -5 M, Tween-80 0.15% and 1.5 mM of Eu 3+ , which allows the determination of 100-1000 ppb of PX with limit of detection (LOD) of 29 ppb. The relative standard deviations of the method range between 0.5% and 3.9% indicating excellent reproducibility of the method. The proposed method was successfully applied for the assay of PX in pharmaceutical formulations and in urine samples. Average recoveries of 100.8±1.7% was obtained in tablet, whereas a recovery of 97.5±2.0% was obtained for the total PX (PX+hydoxy-PX) in urine sample

Lyophilization monophase solution technique for improvement of the solubility and dissolution of piroxicam.

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Dixit, M; Kulkarni, P K

2012-01-01

Piroxicam (PX), an anti-inflammatory drug, exhibits poor water solubility, dissolution and flow properties. Thus, the aim of the present study was to improve the solubility and dissolution rate of PX by freeze drying technique using dimethylformamide (DMF), chloroform and water as co-solvent system. The prepared crystals containing PX were evaluated for DMF and chloroform solvent residual by gas chromatography and solubility and in vitro dissolution. The prepared formulations were characterized by scanning electron microscopy, differential scanning calorimeter; X-ray diffraction and fourier transform infrared spectroscopy. Dissolution profile of the freeze dried crystals was compared with its recrystallized and pure samples. The samples were stored in stability chamber to investigate their physical stability. Solvent residual of DMF and chloroform was found to be within the toxic level. Freeze dried crystals exhibited decreased crystallinity and the solubility and dissolution of the PX crystals were significantly improved compared to its recrystallized and pure samples. In stability test, the release profile of the freeze dried crystals was almost unchanged as compared with the freshly prepared freeze dried crystals stored at 40°C and 75% relative humidity for 90 days. Hence, this technique can be used for formulation of PX tablets by direct compression with directly compressible tablet excipients.

Determination of piroxicam from rat articular tissue and plasma based on LC-MS/MS.

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Kim, Han Sol; Cho, Ha Ra; Ho, Myoung Jin; Kang, Myung Joo; Choi, Yong Seok

2016-12-01

Osteoarthritis (OA) is the most common type of arthritis. To manage OA, in general, oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) is used. Recently, the analgesic and anti-inflammatory efficacy of piroxicam (PX), a long-acting NSAID, by intra-articular (IA) administration in OA was reported, and the possibility that PX is distributed in articular tissues at a certain concentration was raised. Thus, herein, novel LC-MS/MS methods to detect PX in rat articular tissue and plasma are presented. For articular tissue, solvent extraction with acetonitrile for 12 h was employed and a protein precipitation method was used for the preparation of a plasma sample. The developed methods were validated by following the FDA guidelines, and the validated methods were successfully applied to a PK study of IA PX. The present study presents, to our knowledge, the first method of determining a drug in articular tissue. Additionally, the level of PX in articular tissue after IA PX administration was experimentally confirmed for the first time using the present methods. Therefore, the present methods provide a new direction for in vivo evaluation for IA PX formulations and contribute to the development of alternative IA PX formulations with better effects for the treatment of OA.

Ultrasensitive Determination of Piroxicam at Diflunisal-Derived Gold Nanoparticle-Modified Glassy Carbon Electrode

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Shaikh, Tayyaba; uddin, SiraJ; Talpur, Farah N.; Khaskeli, Abdul R.; Agheem, Muhammad H.; Shah, Muhammad R.; Sherazi, Tufail H.; Siddiqui, Samia

2017-10-01

We present a simple and green approach for synthesis of gold nanoparticles (AuNps) using analgesic drug diflunisal (DF) as capping and stabilizing agent in aqueous solution. Characterization of the synthesized diflunisal-derived gold nanoparticles (DF-AuNps) was performed by ultraviolet-visible (UV-Vis) spectroscopy, revealing the surface plasmon absorption band at 520 nm under optimized experimental conditions. Fourier-transform infrared (FTIR) spectroscopy established the effective interaction of the capping agent with the AuNps. Topographical features of the synthesized DF-AuNps were assessed by atomic force microscopy (AFM), revealing average particle height of 29 nm to 32 nm. X-ray diffractometry was used to study the crystalline nature, revealing that the synthesized DF-AuNps possessed excellent crystalline properties. The synthesized DF-AuNps were employed to modify the surface of glassy carbon electrode (GCE) for selective determination of piroxicam (PX) using differential pulse voltammetry technique. The fabricated Nafion/DF-AuNps/GCE sensor exhibited high sensitivity compared with bare GCE. The current response of the fabricated sensor was found to be linear in the PX concentration range of 0.5 μM to 50 μM, with limit of detection (LOD) and limit of quantification (LOQ) of 50 nM and 150 nM, respectively. The proposed sensor was successfully utilized for sensitive and rapid determination of PX in human serum, urine, and pharmaceutical samples.

Indirect spectrophotometric determination of piroxicam and tenoxicam through oxidation with potassium permanganate

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A.S. Amin

2010-04-01

Full Text Available Three rapid, simple, accurate and selective validated spectrophtometric methods (A, B and C for the determination of piroxicam (PX and tenoxicam (TX in bulk sample and in dosage forms are described. The methods are based on the oxidation of the studied drugs by a known excess of potassium permanganate in sulfuric acid medium and subsequent determination of unreacted oxidant by reacting it with Methylene Blue (Basic Blue 9 dye (method A, Acid Red 27 (Amaranth dye (method B and Acid Orange 7 (orange II dye (method C, in the same medium at a suitable λmax = 660, 520 and 485 nm, respectively. The reacted oxidant was found to be corresponding to the drug content. Regression analysis of Beer-Lambert plots showed good correlations in the concentration ranges 1.0-8.0, 1.0-9.0 and 1.0-7.2 μg mL-1 using methods A, B and C, respectively, for PX and 0.3-7.0, 0.3-1.6 and 0.3-2.5 μg mL-1 using methods A, B and C, respectively, for TX. The stoichiometric ratios for the cited drugs to oxidant were studied. The optimum reaction conditions and other analytical parameters were evaluated. The proposed methods were applied successfully to determine the examined drugs either in pure form or pharmaceutical formulations with good accuracy and precision. The relative standard deviations were ≤ 0.33 with recoveries 98.9-101.7% for PX and ≤ 0.49 with recoveries 99.4-102.0% for TX.

Enhancement of solubility, dissolution release profile and reduction in ulcerogenicity of piroxicam by inclusion complex with skimmed milk.

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Sanka, Krishna; Munjulury, Venkata Saidheeraj; Mohd, Abdul Bari; Diwan, Prakash V

2014-11-01

Piroxicam (PXM), a non-steroidal anti-inflammatory drug which is poorly soluble in water and ulcerogenic. Milk has been used against the gastric disturbances caused by non-steroidal anti-inflammatory drugs. In this study, skimmed milk (SKM) is used as the carrier for inclusion complex (IC) due to its surface active agent and amino acid content. To enhance the solubility, dissolution rate and prevent ulcerogenicity of PXM though IC with SKM. IC of PXM were prepared with SKM by solvent evaporation method using rota evaporator and were evaluated for solubility, dissolution, solid state characterization, drug excipient interaction, rat intestinal permeation, ulcerogenicity and histopathological studies. Solubility of PXM was enhanced 2.5 times with IC. The dissolution release and amount of PXM permeated through rat small intestine was enhanced significantly with IC. Decreases in the gastric lesion index values of IC were observed than physical mixture (PM) and free PXM. The histopathological studies revealed significant reduction in ulceration in rat stomach after treatment with IC. It is concluded that SKM is a good carrier to prepare IC of PXM for oral administration.

Increased localized delivery of piroxicam by cationic nanoparticles after intra-articular injection.

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Kim, Sung Rae; Ho, Myoung Jin; Kim, Sang Hyun; Cho, Ha Ra; Kim, Han Sol; Choi, Yong Seok; Choi, Young Wook; Kang, Myung Joo

2016-01-01

Piroxicam (PRX), a potent nonsteroidal anti-inflammatory drug, is prescribed to relieve postoperative and/or chronic joint pain. However, its oral administration often results in serious gastrointestinal adverse effects including duodenal ulceration. Thus, a novel cationic nanoparticle (NP) was explored to minimize the systemic exposure and increase the retention time of PRX in the joint after intra-articular (IA) injection, by forming micrometer-sized electrostatic clusters with endogenous hyaluronic acid (HA) in the synovial cavity. PRX-loaded NPs consisting of poly(lactic- co -glycolic acid), Eudragit RL, and polyvinyl alcohol were constructed with the following characteristics: particle size of 220 nm, zeta potential of 11.5 mV in phosphate-buffered saline, and loading amount of 4.0% (w/w) of PRX. In optical and hyperspectral observations, the cationic NPs formed more than 50 μm-sized aggregates with HA, which was larger than the intercellular gaps between synoviocytes. In an in vivo pharmacokinetic study in rats, area under the plasma concentration-time curve (AUC 0-24 h ) and maximum plasma concentration ( C max ) of PRX after IA injection of the cationic NPs were <70% ( P <0.05) and 60% ( P <0.05), respectively, compared to those obtained from drug solution. Moreover, the drug concentration in joint tissue 24 h after dosing with the cationic NPs was 3.2-fold ( P <0.05) and 1.8-fold ( P <0.05) higher than that from drug solution and neutrally charged NPs, respectively. Therefore, we recommend the IA cationic NP therapy as an effective alternative to traditional oral therapy with PRX, as it increases drug retention selectively in the joint.

Towards improved solubility of poorly water-soluble drugs: cryogenic co-grinding of piroxicam with carrier polymers.

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Penkina, Anna; Semjonov, Kristian; Hakola, Maija; Vuorinen, Sirpa; Repo, Timo; Yliruusi, Jouko; Aruväli, Jaan; Kogermann, Karin; Veski, Peep; Heinämäki, Jyrki

2016-01-01

Amorphous solid dispersions (SDs) open up exciting opportunities in formulating poorly water-soluble active pharmaceutical ingredients (APIs). In the present study, novel catalytic pretreated softwood cellulose (CPSC) and polyvinylpyrrolidone (PVP) were investigated as carrier polymers for preparing and stabilizing cryogenic co-ground SDs of poorly water-soluble piroxicam (PRX). CPSC was isolated from pine wood (Pinus sylvestris). Raman and Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used for characterizing the solid-state changes and drug-polymer interactions. High-resolution scanning electron microscope (SEM) was used to analyze the particle size and surface morphology of starting materials and final cryogenic co-ground SDs. In addition, the molecular aspects of drug-polymer interactions and stabilization mechanisms are presented. The results showed that the carrier polymer influenced both the degree of amorphization of PRX and stabilization against crystallization. The cryogenic co-ground SDs prepared from PVP showed an enhanced dissolution rate of PRX, while the corresponding SDs prepared from CPSC exhibited a clear sustained release behavior. In conclusion, cryogenic co-grinding provides a versatile method for preparing amorphous SDs of poorly water-soluble APIs. The solid-state stability and dissolution behavior of such co-ground SDs are to a great extent dependent on the carrier polymer used.

Structural and thermal characterization of ternary complexes of piroxicam and alanine with transition metals: Uranyl binary and ternary complexes of piroxicam. Spectroscopic characterization and properties of metal complexes

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Mohamed, Gehad G.

2005-12-01

Ternary Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and UO 2(II) complexes with piroxicam (Pir) drug (H 2L 1) and dl-alanine (Ala) (HL 2) and also the binary UO 2(II) complex with Pir were studied. The structures of the complexes were elucidated using elemental, IR, molar conductance, magnetic moment, diffused reflectance and thermal analyses. The UO 2(II) binary complex was isolated in 1:2 ratio with the formula [UO 2(H 2L) 2](NO 3) 2. The ternary complexes were isolated in 1:1:1 (M:H 2L 1:L 2) ratios. The solid complexes were isolated in the general formulae [M(H 2L)(L 2)(Cl) n(H 2O) m]· yH 2O (M = Fe(III) ( n = 2, m = 0, y = 1), Co(II) ( n = 1, m = 1, y = 2) and Ni(II) ( n = 1, m = 1, y = 0)); [M(H 2L)(L 2)](X) z· yH 2O (M = Cu(II) (X = AcO, z = 1, y = 0), Zn(II) (X = AcO, z = 1, y = 3) and UO 2(II) (X = NO 3, z = 1, y = 2)). Pir behaves as a neutral bidentate ligand coordinated to the metal ions via the pyridine-N and carbonyl-O groups, while Ala behaves as a uninegatively bidentate ligand coordinated to the metal ions via the deprotonated carboxylate-O and amino-N. The magnetic and reflectance spectral data show that the complexes have octahedral geometry except Cu(II) and Zn(II) complexes have tetrahedral structures. The thermal decomposition of the complexes was discussed in relation to structure, and the thermodynamic parameters of the decomposition stages were evaluated.

Effects of low-dose cyclophosphamide with piroxicam on tumour neovascularization in a canine oral malignant melanoma-xenografted mouse model.

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Choisunirachon, N; Jaroensong, T; Yoshida, K; Saeki, K; Mochizuki, M; Nishimura, R; Sasaki, N; Nakagawa, T

2015-12-01

Low-dose cyclophosphamide (CyLD) has shown promise in the treatment of several cancers; however, the effect of CyLD on canine oral malignant melanoma has never been explored. In this study, we investigated the effects of CyLD with or without piroxicam (Px) on tumour neovascularization and vascular normalization in a canine oral malignant melanoma-xenografted mice model. After treatment with CyLD, Px or a combination of both (CyPx), the growth of the tumour in the treatment groups was significantly suppressed compared to the control group at 30 days of treatment. Proliferation index was also significantly reduced by all treatments, only CyPx significantly lowered microvessel density and vascular endothelial growth factor (VEGF) levels. Additionally, CyLD significantly reduced the proportion of normal vessels and caused an imbalance between VEGF and thrombospondin-1. These results suggested that CyPx has potent anti-angiogenic effects in terms of both the number and quality of blood vessels in xenografted canine oral malignant melanoma. © 2013 John Wiley & Sons Ltd.

Efficacy of a Film-Forming Medical Device Containing Piroxicam and Sun Filters in the Treatment of Multiple Actinic Keratosis Lesions in a Subject with a History of Kaposi Sarcoma

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Elisabetta Scotti

2016-10-01

Full Text Available Actinic keratosis (AK is considered a premalignant form of skin cancer due to chronic sun exposure. In addition, human papilloma virus (HPV has been advocated a role in the pathogenesis of this clinical condition. HPV proteins (mainly E6 and E7 seem to act synergistically with ultraviolet (UV radiation in reducing the defensive mechanisms of keratinocyte apoptosis after UV damage. Data regarding the involvement of other viruses, i.e. human herpes viruses (HHV, in the pathogenesis of AK are so far controversial. HHV8 is considered the infective agent involved in the development of Kaposi sarcoma. Some experimental data have shown that AK lesions carry HHV8 in more than 30% of the bioptic samples. Topical piroxicam was shown to be effective in the treatment of AK. In addition, the molecule shows antiviral action against HPV and HHV8. Here, we report the efficacy of a medical device containing a film-forming substance (polyvinyl alcohol, chemical and physical sun filters (SPF 50+, and 0.8% piroxicam (ActixicamTM, Difa Cooper; ACTX in the treatment of multiple scalp AK lesions, unresponsive to other treatments, in a subject with Kaposi sarcoma and a history of severe contact dermatitis. The subject presented with severe involvement of the scalp, with multiple hypertrophic AK lesions. Previous lesion-directed and field-targeted treatments have not been effective. The subject was treated with ACTX applied twice daily on the affected scalp. Relevant clinical improvement was observed as soon as 1 month of therapy. Complete clinical resolution of all scalp lesions was observed after 3 months of treatment. The product was well tolerated.

Synthesis of piroxicam loaded novel electrospun biodegradable nanocomposite scaffolds for periodontal regeneration

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Farooq, Ariba [Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Yar, Muhammad, E-mail: drmyar@ciitlahore.edu.pk [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Khan, Abdul Samad; Shahzadi, Lubna; Siddiqi, Saadat Anwar [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Mahmood, Nasir [Department of Allied Health Sciences and Chemical Pathology, University of Health Sciences, Lahore (Pakistan); Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore (Pakistan); Rauf, Abdul [Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Qureshi, Zafar-ul-Ahsan [Veterinary Research Institute, Lahore (Pakistan); Manzoor, Faisal; Chaudhry, Aqif Anwar [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Rehman, Ihtesham ur [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore,54000 (Pakistan); Department of Materials Science and Engineering, The Kroto Research Institute, The University of Sheffield, North Campus, Broad Lane, Sheffield S3 7HQ (United Kingdom)

2015-11-01

Development of biodegradable composites having the ability to suppress or eliminate the pathogenic micro-biota or modulate the inflammatory response has attracted great interest in order to limit/repair periodontal tissue destruction. The present report includes the development of non-steroidal anti-inflammatory drug encapsulated novel biodegradable chitosan (CS)/poly(vinyl alcohol) (PVA)/hydroxyapatite (HA) electro-spun (e-spun) composite nanofibrous mats and films and study of the effect of heat treatment on fibers and films morphology. It also describes comparative in-vitro drug release profiles from heat treated and control (non-heat treated) nanofibrous mats and films containing varying concentrations of piroxicam (PX). Electrospinning was used to obtain drug loaded ultrafine fibrous mats. The physical/chemical interactions were evaluated by Fourier Transform Infrared (FT-IR) spectroscopy. The morphology, structure and pore size of the materials were investigated by scanning electron microscopy (SEM). The thermal behavior of the materials was investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Control (not heat treated) and heat treated e-spun fibers mats and films were tested for in vitro drug release studies at physiological pH 7.4 and initially, as per requirement burst release patterns were observed from both fibers and films and later sustained release profiles were noted. In vitro cytocompatibility was performed using VERO cell line of epithelial cells and all the synthesized materials were found to be non-cytotoxic. The current observations suggested that these materials are potential candidates for periodontal regeneration. - Highlights: • Novel non-steroidal anti-inflammatory drug encapsulated biodegradable electrospun nanocomposite scaffolds were synthesized. • Heat treatment displayed great influence on the morphology of scaffolds. • Fiber diameter was decreased and pore size was increased after heat

Synthesis of piroxicam loaded novel electrospun biodegradable nanocomposite scaffolds for periodontal regeneration

International Nuclear Information System (INIS)

Farooq, Ariba; Yar, Muhammad; Khan, Abdul Samad; Shahzadi, Lubna; Siddiqi, Saadat Anwar; Mahmood, Nasir; Rauf, Abdul; Qureshi, Zafar-ul-Ahsan; Manzoor, Faisal; Chaudhry, Aqif Anwar; Rehman, Ihtesham ur

2015-01-01

Development of biodegradable composites having the ability to suppress or eliminate the pathogenic micro-biota or modulate the inflammatory response has attracted great interest in order to limit/repair periodontal tissue destruction. The present report includes the development of non-steroidal anti-inflammatory drug encapsulated novel biodegradable chitosan (CS)/poly(vinyl alcohol) (PVA)/hydroxyapatite (HA) electro-spun (e-spun) composite nanofibrous mats and films and study of the effect of heat treatment on fibers and films morphology. It also describes comparative in-vitro drug release profiles from heat treated and control (non-heat treated) nanofibrous mats and films containing varying concentrations of piroxicam (PX). Electrospinning was used to obtain drug loaded ultrafine fibrous mats. The physical/chemical interactions were evaluated by Fourier Transform Infrared (FT-IR) spectroscopy. The morphology, structure and pore size of the materials were investigated by scanning electron microscopy (SEM). The thermal behavior of the materials was investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Control (not heat treated) and heat treated e-spun fibers mats and films were tested for in vitro drug release studies at physiological pH 7.4 and initially, as per requirement burst release patterns were observed from both fibers and films and later sustained release profiles were noted. In vitro cytocompatibility was performed using VERO cell line of epithelial cells and all the synthesized materials were found to be non-cytotoxic. The current observations suggested that these materials are potential candidates for periodontal regeneration. - Highlights: • Novel non-steroidal anti-inflammatory drug encapsulated biodegradable electrospun nanocomposite scaffolds were synthesized. • Heat treatment displayed great influence on the morphology of scaffolds. • Fiber diameter was decreased and pore size was increased after heat

Solid-state, triboelectrostatic and dissolution characteristics of spray-dried piroxicam-glucosamine solid dispersions.

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Adebisi, Adeola O; Kaialy, Waseem; Hussain, Tariq; Al-Hamidi, Hiba; Nokhodchi, Ali; Conway, Barbara R; Asare-Addo, Kofi

2016-10-01

This work explores the use of both spray drying and d-glucosamine HCl (GLU) as a hydrophilic carrier to improve the dissolution rate of piroxicam (PXM) whilst investigating the electrostatic charges associated with the spray drying process. Spray dried PXM:GLU solid dispersions were prepared and characterised (XRPD, DSC, SEM). Dissolution and triboelectric charging were also conducted. The results showed that the spray dried PXM alone, without GLU produced some PXM form II (DSC results) with no enhancement in solubility relative to that of the parent PXM. XRPD results also showed the spray drying process to decrease the crystallinity of GLU and solid dispersions produced. The presence of GLU improved the dissolution rate of PXM. Spray dried PXM: GLU at a ratio of 2:1 had the most improved dissolution. The spray drying process generally yielded PXM-GLU spherical particles of around 2.5μm which may have contributed to the improved dissolution. PXM showed a higher tendency for charging in comparison to the carrier GLU (-3.8 versus 0.5nC/g for untreated material and -7.5 versus 3.1nC/g for spray dried materials). Spray dried PXM and spray dried GLU demonstrated higher charge densities than untreated PXM and untreated GLU, respectively. Regardless of PXM:GLU ratio, all spray dried PXM:GLU solid dispersions showed a negligible charge density (net-CMR: 0.1-0.3nC/g). Spray drying of PXM:GLU solid dispersions can be used to produce formulation powders with practically no charge and thereby improving handling as well as dissolution behaviour of PXM. Copyright © 2016 Elsevier B.V. All rights reserved.

Inclusion of piroxicam in mesoporous phosphate glass-ceramic and evaluation of the physiochemical characteristics.

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Javadzadeh, Yousef; Bairami Atashgah, Rahimeh; Barzegar-Jalali, Mohammad; Soleimani, Farshad; Mohammadi, Ghobad; Sabzevari, Araz; Adibkia, Khosro

2014-04-01

The mesoporous glass-ceramic (GC) was employed as a carrier to investigate its capability for pharmaceutical applications. Piroxicam (PX) as a model drug was loaded in the GC by using of solvent evaporation technique. The physicochemical properties and morphology of the powders were evaluated employing X-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). The drug adsorption isotherms were assessed as well. Drug release profiles were examined by fitting the data to the 10 common kinetic models. The specific surface area, Vm (the volume of the N2 adsorbed on the 1g of the GC when the monolayer is complete) and the average pore diameter of the GC powder before and after loading process were measured by the Brunauer-Emmett-Teller (BET) and Barrett-Joyner-Halenda (BJH) analysis benefiting N2 adsorption/desorption isotherms. The ideal loading of PX in the GC was 41.8%. The average pore diameter for the GC was determined to be about 10nm. The Freundlich model was found to be the best adsorption isotherm. Decrease of the GC specific surface area and Vm values were observed after loading process. Drug release data were best fitted to the Weibull model with the shape factor of 0.4-0.7 signifying the Fickian diffusion of PX from the GC. Accordingly, the GC could be considered as a suitable adsorbent to develop an oral drug delivery system. Copyright © 2014 Elsevier B.V. All rights reserved.

Piroxicam, a traditional non-steroidal anti-inflammatory drug (NSAID) causes apoptosis by ROS mediated Akt activation.

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Rai, Neha; Sarkar, Munna; Raha, Sanghamitra

2015-12-01

Piroxicam (Px) belongs to the oxicam group of the non-steroidal anti-inflammatory drugs (NSAIDs) and have been shown to exert chemopreventive and chemotherapeutic effects in animal models and cultured animal cells. However, little is known about the mode of action of Px and its cellular targets. We explored the role of Px, in triggering apoptosis and examined the involvement of upstream cellular mechanisms in apoptosis induction by Px. Our studies with human breast cancer cells MCF-7 show that Px induces reactive oxygen species (ROS) generation along with apoptotic cell death. ROS release lead to Akt activation. On evaluation it became evident that ROS mediated apoptosis induction was due to Akt activation (hyper phosphorylation). Silencing the expression of Akt using siRNA and a specific Akt inhibitor, triciribine further confirmed the findings. However Px failed to cause ROS generation, cell death or Akt phosphorylation in another human breast cancer cells MDA-MB-231 which is estrogen receptor negative and more aggressive compared to MCF-7 cells. This suggests that Px has cell type specific effects. Thus we revealed for the first time that Px can induce apoptosis by ROS mediated Akt hyperphosphorylation/activation. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

A mononuclear zinc(II) complex with piroxicam: Crystal structure, DNA- and BSA-binding studies; in vitro cell cytotoxicity and molecular modeling of oxicam complexes

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Jannesari, Zahra; Hadadzadeh, Hassan; Amirghofran, Zahra; Simpson, Jim; Khayamian, Taghi; Maleki, Batool

2015-02-01

A new mononuclear Zn(II) complex, trans-[Zn(Pir)2(DMSO)2], where Pir- is 4-hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (piroxicam), has been synthesized and characterized. The crystal structure of the complex was obtained by the single crystal X-ray diffraction technique. The interaction of the complex with DNA and BSA was investigated. The complex interacts with FS-DNA by two binding modes, viz., electrostatic and groove binding (major and minor). The microenvironment and the secondary structure of BSA are changed in the presence of the complex. The anticancer effects of the seven complexes of oxicam family were also determined on the human K562 cell lines and the results showed reasonable cytotoxicities. The interactions of the oxicam complexes with BSA and DNA were modeled by molecular docking and molecular dynamic simulation methods.

Colon specific CODES based Piroxicam tablet for colon targeting: statistical optimization, in vivo roentgenography and stability assessment.

Science.gov (United States)

Singh, Amit Kumar; Pathak, Kamla

2015-03-01

This study was aimed to statistically optimize CODES™ based Piroxicam (PXM) tablet for colon targeting. A 3(2) full factorial design was used for preparation of core tablet that was subsequently coated to get CODES™ based tablet. The experimental design of core tablets comprised of two independent variables: amount of lactulose and PEG 6000, each at three different levels and the dependent variable was %CDR at 12 h. The core tablets were evaluated for pharmacopoeial and non-pharmacopoeial test and coated with optimized levels of Eudragit E100 followed by HPMC K15 and finally with Eudragit S100. The in vitro drug release study of F1-F9 was carried out by change over media method (0.1 N HCl buffer, pH 1.2, phosphate buffer, pH 7.4 and phosphate buffer, pH 6.8 with enzyme β-galactosidase 120 IU) to select optimized formulation F9 that was subjected to in vivo roentgenography. Roentgenography study corroborated the in vitro performance, thus providing the proof of concept. The experimental design was validated by extra check point formulation and Diffuse Reflectance Spectroscopy revealed absence of any interaction between drug and formulation excipients. The shelf life of F9 was deduced as 12 months. Conclusively, colon targeted CODES™ technology based PXM tablets were successfully optimized and its potential of colon targeting was validated by roentgenography.

Structure investigation, spectral, thermal, X-ray and mass characterization of piroxicam and its metal complexes

Science.gov (United States)

Zayed, M. A.; Nour El-Dien, F. A.; Mohamed, Gehad G.; El-Gamel, Nadia E. A.

2004-10-01

[M(H 2L) 2](A) 2. yH 2O (where H 2L: neutral piroxicam (Pir), A: Cl - in case of Ni(II) or acetate anion in case of Cu(II) and Zn(II) ions and y=0-2.5) and [M(H 2L) 3](A) z. yH 2O (A: SO 42- in case of Fe(II) ion ( z=1) or Cl - in case of Fe(III) ( z=3) and Co(II) ions ( z=2) and y=1-4) chelates are prepared and characterized using elemental analyses, IR, magnetic and electronic reflectance measurements, mass spectra and thermal analyses. IR spectra reveal that Pir behaves a neutral bidentate ligand coordinated to the metal ions through the pyridyl-N and carbonyl-O of the amide moiety. The reflectance and magnetic moment measurements reveal that these chelates have tetrahedral, square planar and octahedral geometrical structures. Mass spectra and thermal analyses are also used to confirm the proposed formulae and the possible fragments resulted from fragmentation of Pir and its chelates. The thermal behaviour of the chelates (TGA and DTA) are discussed in detail and the thermal stability of the anhydrous chelates follow the order Ni(II)≅Cu(II)

The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors.

Science.gov (United States)

Campione, Elena; Paternò, Evelin Jasmine; Candi, Eleonora; Falconi, Mattia; Costanza, Gaetana; Diluvio, Laura; Terrinoni, Alessandro; Bianchi, Luca; Orlandi, Augusto

2015-01-01

Piroxicam (PXM), a nonsteroidal anti-inflammatory drug, is an enolic benzothiazine and a potent member of the oxicam series. The drug suppresses the synthesis of proinflammatory enzymes, such as cyclo-oxygenases-1 and -2 (COX-1 and 2), downregulates the production of prostaglandins (PGs) and tromboxanes, and inhibits polyamines production by blocking ornithine decarboxylase induction involved in nonmelanoma skin carcinogenesis. In addition, PXM is able to induce tumor cell apoptosis and suppresses metalloproteinase 2 activities. Skin carcinogenesis is a multistep process in which the accumulation of genetic events leads to a gradually dysplastic cellular expression, deregulation of cell growth, and carcinomatous progression. COX-1 upregulation plays a significant role in PG and vascular epidermal growth factor production supporting tumor growth. Increased level of PGs in premalignant and/or malignant cutaneous tumors is also favored by upregulation of COX-2 and downregulation of the tumor suppressor gene 15-hydroxy-prostaglandin dehydrogenase. Chemoprevention can be a hopeful approach to inhibit carcinoma occurrence before an invasive tumor develops. The chemopreventive effect of nonsteroidal anti-inflammatory drugs on nonmelanoma skin cancers has been established. In this study, we highlighted the different modalities of action of PXM on the pathogenesis of nonmelanoma skin cancer, analyzing and evaluating binding modes and energies between COX-1 or COX-2 and PXM by protein-ligand molecular docking. Our clinical experience about the local use of PXM on actinic keratoses and field cancerization is also reported, confirming its efficacy as target therapy.

A high sensitive biosensor based on FePt/CNTs nanocomposite/N-(4-hydroxyphenyl)-3,5-dinitrobenzamide modified carbon paste electrode for simultaneous determination of glutathione and piroxicam.

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Karimi-Maleh, Hassan; Tahernejad-Javazmi, Fahimeh; Ensafi, Ali A; Moradi, Reza; Mallakpour, Shadpour; Beitollahi, Hadi

2014-10-15

This study describes the development, electrochemical characterization and utilization of novel modified N-(4-hydroxyphenyl)-3,5-dinitrobenzamide-FePt/CNTs carbon paste electrode for the electrocatalytic determination of glutathione (GSH) in the presence of piroxicam (PXM) for the first time. The synthesized nanocomposite was characterized with different methods such as TEM and XRD. The modified electrode exhibited a potent and persistent electron mediating behavior followed by well-separated oxidation peaks of GSH and PXM. The peak currents were linearly dependent on GSH and PXM concentrations in the range of 0.004-340 and 0.5-550 µmol L(-1), with detection limits of 1.0 nmol L(-1) and 0.1 µmolL(-1), respectively. The modified electrode was successfully used for the determination of the analytes in real samples with satisfactory results. Copyright © 2014 Elsevier B.V. All rights reserved.

Diseño y validación de un método espectrofotométrico para el control de calidad del piroxicam jalea 0,5 %

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Yania Suárez Pérez

Full Text Available La jalea de piroxicam al 0,5 % es un nuevo producto en fase de desarrollo de la Empresa Laboratorio "Roberto Escudero Díaz". En el presente trabajo se diseñó un método por espectrofotometría UV, para lo cual se empleó ácido clorhídrico etanólico como disolvente y 328 nm como longitud de onda de máxima absorción. Se estableció un procedimiento simple y rápido para procesar la muestra previa al análisis. Posteriormente se aplicó la validación de este según exigencias regulatorias actuales. El método resultó suficientemente específico, lineal, preciso y exacto en el rango de 3,125 a 9,375 µg/mL. Se aplicó a la cuantificación del principio activo en 3 lotes de la formulación desarrollada, con resultados satisfactorios sin diferencias estadísticamente significativas según el procesamiento aplicado.

Preparation of Microcrystals of Piroxicam Monohydrate by Antisolvent Precipitation via Microfabricated Metallic Membranes with Ordered Pore Arrays.

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Othman, Rahimah; Vladisavljević, Goran T; Simone, Elena; Nagy, Zoltan K; Holdich, Richard G

2017-12-06

Microcrystals of piroxicam (PRX) monohydrate with a narrow size distribution were prepared from acetone/PRX solutions by antisolvent crystallization via metallic membranes with ordered pore arrays. Crystallization was achieved by controlled addition of the feed solution through the membrane pores into a well-stirred antisolvent. A complete transformation of an anhydrous form I into a monohydrate form of PRX was confirmed by Raman spectroscopy and differential scanning calorimetry. The size of the crystals was 7-34 μm and was controlled by the PRX concentration in the feed solution (15-25 g L -1 ), antisolvent/solvent volume ratio (5-30), and type of antisolvent (Milli-Q water or 0.1-0.5 wt % aqueous solutions of hydroxypropyl methyl cellulose (HPMC), poly(vinyl alcohol) or Pluronic P-123). The smallest crystals were obtained by injecting 25 g L -1 PRX solution through a stainless-steel membrane with a pore size of 10 μm into a 0.06 wt % HPMC solution stirred at 1500 rpm using an antisolvent/solvent ratio of 20. HPMC provided better steric stabilization of microcrystals against agglomeration than poly(vinyl alcohol) and Pluronic P-123, due to hydrogen bonding interactions with PRX and water. A continuous production of large PRX monohydrate microcrystals with a volume-weighted mean diameter above 75 μm was achieved in a continuous stirred membrane crystallizer. Rapid pouring of Milli-Q water into the feed solution resulted in a mixture of highly polydispersed prism-shaped and needle-shaped crystals.

Template occluded SBA-15: An effective dissolution enhancer for poorly water-soluble drug

International Nuclear Information System (INIS)

Fu Tingming; Guo Liwei; Le Kang; Wang Tianyao; Lu Jin

2010-01-01

The aim of the present work was to improve the dissolution rate of piroxicam by inclusion into template occluded SBA-15. Our strategy involves directly introducing piroxicam into as-prepared SBA-15 occluded with P123 (EO 20 PO 70 EO 20 ) by self assembling method in acetonitrile/methylene chloride mixture solution. Ultraviolet spectrometry experiment and thermogravimetric analysis-differential scanning calorimetry (TG-DSC) profiles show that the piroxicam and P123 contents in the inclusion compound are 12 wt% and 28 wt%, respectively. X-ray powder diffraction and DSC analysis reveal that the included piroxicam is arranged in amorphous form. N 2 adsorption-desorption experiment indicates that the piroxicam has been introduced to the mesopores instead of precipitating at the outside of the silica material. The inclusion compound was submitted to in vitro dissolution tests, the results show that the piroxicam dissolve from template occluded inclusion compound more rapidly, than these from the piroxicam crystalline and template removed samples in all tested conditions. Thus a facile method to improve the dissolution rate of poorly water-soluble drug was established, and this discovery opens a new avenue for the utilization of templates used for the synthesis of mesoporous materials.

Template occluded SBA-15: An effective dissolution enhancer for poorly water-soluble drug

Energy Technology Data Exchange (ETDEWEB)

Fu Tingming, E-mail: futingming@gmail.com [College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029 (China); Guo Liwei; Le Kang; Wang Tianyao; Lu Jin [College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029 (China)

2010-09-15

The aim of the present work was to improve the dissolution rate of piroxicam by inclusion into template occluded SBA-15. Our strategy involves directly introducing piroxicam into as-prepared SBA-15 occluded with P123 (EO{sub 20}PO{sub 70}EO{sub 20}) by self assembling method in acetonitrile/methylene chloride mixture solution. Ultraviolet spectrometry experiment and thermogravimetric analysis-differential scanning calorimetry (TG-DSC) profiles show that the piroxicam and P123 contents in the inclusion compound are 12 wt% and 28 wt%, respectively. X-ray powder diffraction and DSC analysis reveal that the included piroxicam is arranged in amorphous form. N{sub 2} adsorption-desorption experiment indicates that the piroxicam has been introduced to the mesopores instead of precipitating at the outside of the silica material. The inclusion compound was submitted to in vitro dissolution tests, the results show that the piroxicam dissolve from template occluded inclusion compound more rapidly, than these from the piroxicam crystalline and template removed samples in all tested conditions. Thus a facile method to improve the dissolution rate of poorly water-soluble drug was established, and this discovery opens a new avenue for the utilization of templates used for the synthesis of mesoporous materials.

A long-term randomised trial on tenoxicam and piroxicam in osteoarthritis of the hip or knee: a 24-month interim report focusing on the 12-24 month interval

DEFF Research Database (Denmark)

Lund, B; Andersen, R B; Fossgreen, J

1987-01-01

The long-acting antiphlogistics tenoxicam (Ro 12-0068, Tilcotil) and piroxicam in single daily oral doses of 20 mg are compared in a double-blind, group-comparative, randomised trial planned to last for five years. Results of 12 months' treatment of 108 patients with osteoarthritis of the hip...... or knee have been reported. This interim analysis focuses mainly on the 12 to 24 month interval. The clinical improvements obtained within the first 12 months persisted during the second year in the 55 patients remaining on treatment. After 24 months, 53 patients had been withdrawn prematurely, three......-quarters because of inefficacy or intolerance. Only six patients were withdrawn between 12 and 24 months, three for lack of efficacy, two for side-effects and one for reasons unrelated to therapy. There was no difference between the treatment groups with regard to incidence, time or reason for withdrawal, and only...

Quantitative Analysis of Piroxicam Using Temperature-Controlled Ionic Liquid Dispersive Liquid Phase Microextraction Followed By Stopped-Flow Injection Spectrofluorimetry

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Mohammad Reza Ganjali

2013-07-01

Full Text Available Background:Piroxicam (PXM belongs to the wide class of non-steroidal anti-inflammatory drugs (NSAIDs. PXM has been widely applied in the treatment of rheumatoid arthritis, gonarthrosis, osteoarthritis, backaches, neuralgia, mialgia. In the presented work, a green and benign sample pretreatment method called temperature-controlled ionic liquid dispersive liquid phase microextraction (TCIL-DLPME was followed with stopped-flow injection spectrofluorimetry (SFIS for quantitation of PXM in pharmaceutical formulations and biological samples.Methods:Temperature-controlled ionic liquid dispersive liquid phase microextraction (TCIL-DLPME was applied as an environmentally friendly sample enrichment method to extract and isolate PXM prior to quantitation. Dispersion of 1-hexyl-3-methylimidazolium hexafluorophosphate ([Hmim][PF6] ionic liquid (IL through the sample aqueous solution was performed by applying a relatively high temperature. PXM was extracted into the extractor, and after phase separation, PXM in the final solution was determined by stopped-flow injection spectrofluorimetry (SFIS.Results and Major Conclusion:Different factors affecting the designed method such as IL amount, diluting agent, pH and temperature were investigated in details and optimized. The method provided a linear dynamic range of 0.2-150 μg l-1, a limit of detection (LOD of 0.046 μg l-1 and a relative standard deviation (RSD of 3.1%. Furthermore, in order to demonstrate the analytical applicability of the recommended method, it was applied for quantitation of PXM in real samples.

Analysis of Piroxicam in Pharmaceutical Formulation and Human Urine by Dispersive Liquid–Liquid Microextraction Combined with Spectrophotometry

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Nakisa Seyyedeh Tutunchi

2013-02-01

Full Text Available Purpose: Piroxicam, is non–steroidal anti–inflammatory and analgesic agent, which is widely used in the treatment of patients with rheumatologic disorders. A new analytical approach based on the dispersive liquid–liquid microextraction (DLLME has been developed for the extraction and determination of PX in pharmaceutical preparation and human urine. Methods: From the PX standard solution or solutions prepared from real samples, aliquot volumes were pipetted into centrifuge tubes and mixed with acetate buffer at pH 3.0 and NaCl solution. The contents were subjected to the DLLME, so 700 μL of methanol containing 70 μL of chloroform was injected rapidly into a sample solution. A cloudy solution was rapidly produced and the PX extracted into dispersed fine droplets. The mixture was centrifuged, thus these fine droplets of chloroform were settled. The supernatant aqueous phase was readily decanted, then the remained organic phase was diluted with ethanol and the absorbance measured at 355 ± 3 nm against a reagent blank. Results: The main factors affecting the extraction efficiency such as pH, extraction and disperser solvent types and etc. were studied and optimized systematically. Under optimized conditions, the calibration graphs were linear over the range of 0.2 to 4.8 μg/mL. The limit of detection and relative standard deviation were found to be 0.058 μg/mL and 2.83%, respectively. Relative recoveries in the spiked samples ranged from 97 to 110%. Conclusion: Using the developed method PX can be analyzed in pharmaceutical formulation and human urine sample in a simpler, cheaper and more rapid manner.

Microemulsions containing long-chain oil ethyl oleate improve the oral bioavailability of piroxicam by increasing drug solubility and lymphatic transportation simultaneously.

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Xing, Qiao; Song, Jia; You, Xiuhua; Xu, Dongling; Wang, Kexin; Song, Jiaqi; Guo, Qin; Li, Pengyu; Wu, Chuanbin; Hu, Haiyan

2016-09-25

Drug solubility and lymphatic transport enhancements are two main pathways to improve drug oral bioavailability for microemulsions. However, it is not easy to have both achieved simultaneously because excipients used for improving lymphatic transport were usually insufficient in forming microemulsions and solubilizing drugs. Our research is to explore whether ethyl oleate, an oil effective in developing microemulsions with desired solubilizing capability, could increase bioavailability to a higher extent by enhancing lymphatic transport. As a long-chain oil, ethyl oleate won larger microemulsion area than short-chain tributyrin and medium-chain GTCC. In contrast, long-chain soybean oil failed to prepare microemulsions. The solubility of piroxicam in ethyl oleate microemulsions (ME-C) increased by about 30 times than in water. ME-C also won significantly higher AUC0-t compared with tributyrin microemulsions (ME-A) and GTCC microemulsions (ME-B). Oral bioavailability in ME-C decreased by 38% after lymphatic transport was blocked by cycloheximide, severer than those in ME-A and ME-B (8% and 34%). These results suggest that improving lymphatic transport and solubility simultaneously might be a novel strategy to increase drug oral bioavailability to a higher extent than increasing solubility only. Ethyl oleate is a preferred oil candidate due to its integrated advantages of high solubilizing capability, large microemulsion area and effective lymphatic transport. Copyright © 2016 Elsevier B.V. All rights reserved.

Drug release into hydrogel-based subcutaneous surrogates studied by UV imaging

DEFF Research Database (Denmark)

Ye, Fengbin; Larsen, Susan Weng; Yaghmur, Anan

2012-01-01

of the performance of drug delivery systems based on in vitro experiments. The objective of this study was to evaluate a UV imaging-based method for real-time characterization of the release and transport of piroxicam in hydrogel-based subcutaneous tissue mimics/surrogates. Piroxicam partitioning from medium chain...... upon the injection of aqueous or MCT solutions into an agarose-based hydrogel were investigated by UV imaging. The spatial distribution of piroxicam around the injection site in the gel matrix was monitored in real-time. The disappearance profiles of piroxicam from the injected aqueous solution were...... obtained. This study shows that the UV imaging methodology has considerable potential for characterizing transport properties in hydrogels, including monitoring the real-time spatial concentration distribution in vitro after administration by injection....

Validace HPLC metody stanovení piroxikamu v plasmě s využitím SPME a deproteinace

OpenAIRE

Kuželová, Kristýna

2015-01-01

Validation of HPLC evaluatoin of piroxicam in plasma using SPME and precipitation Rigorous Thesis Mgr. Kristýna Kuželová Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Department of Pharmaceutical Chemistry and Drug Control, Heyrovského 1203, Hradec Králové The purpose of this thesis was bioanalytical evalution of piroxicam using High Performance Liquid Chromatagraphy (HPLC). Piroxicam was isolated from plasma using SPME and protein precipitacion. Plasma was adjusted to ...

Aspirin and Extended-Release Dipyridamole

Science.gov (United States)

... Mobic), nabumetone (Relafen), naproxen (Aleve, Naprosyn), oxaprozin (Daypro), piroxicam (Feldene), rofecoxib (Vioxx) (no longer available in the ... Mobic), nabumetone (Relafen), naproxen (Aleve, Naprosyn), oxaprozin (Daypro), piroxicam (Feldene), sulindac (Clinoril), and tolmetin (Tolectin); phenytoin (Dilantin); ...

Sensitive and selective spectrophotometric assay of piroxicam in pure form, capsule and human blood serum samples via ion-pair complex formation

Science.gov (United States)

Alizadeh, Nina; Keyhanian, Fereshteh

2014-09-01

A simple, accurate and highly sensitive spectrophotometric method has been developed for the rapid determination of piroxicam (PX) in pure and pharmaceutical formulations. The proposed method involves formation of stable yellow colored ion-pair complexes of the amino derivative (basic nitrogen) of PX with three sulphonphthalein acid dyes namely; bromocresol green (BCG), bromothymol blue (BTB), bromophenol blue (BPB) in acidic medium. The colored species exhibited absorption maxima at 438, 429 and 432 nm with molar absorptivity values of 9.400 × 103, 1.218 × 103 and 1.02 × 104 L mol-1 cm-1 for PX-BCG, PX-BTB and PX-BPB complexes, respectively. The effect of optimum conditions via acidity, reagent concentration, time and solvent were studied. The reactions were extremely rapid at room temperature and the absorbance values remained constant for 48 h. Beer’s law was obeyed with a good correlation coefficient in the concentration ranges 1-100 μg mL-1 for BCG, BTB complexes and 1-95 μg mL-1 for BPB complex. The composition ratio of the ion-pair complexes were found to be 1:1 in all cases as established by Job’s method. No interference was observed from common additives and excipients which may be present in the pharmaceutical preparations. The proposed method was successfully applied for the determination of PX in capsule and human blood serum samples with good accuracy and precision.

Synthesis and thermal characterization of new ternary chelates of piroxicam and tenoxicam with glycine and DL-phenylalanine and some transition metals

Science.gov (United States)

Zayed, M. A.; El-Dien, F. A. Nour; Mohamed, Gehad G.; El-Gamel, Nadia E. A.

2006-05-01

The ternary chelates of piroxicam (Pir) and tenoxicam (Ten) with Fe(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) in the presence of various amino acids such as glycine (Gly) or DL-phenylalanine (PhA) were prepared and characterized with different physicochemical methods. IR spectra confirm that Pir and Ten behave as a neutral bidentate ligand coordinated to the metal ions via the pyridine- N and carbonyl group of the amide moiety. Gly molecule acted as a uninegatively monodentate ligand and coordinate to the metal ions through its deprotonated carboxylic group. In addition, PhA acted as a uninegatively bidentate ligand and coordinate to the metal ions through its deprotonated carboxylic and amino groups. The solid reflectance spectra and magnetic moment measurements confirm that all the chelates have octahedral geometrical structures while Cu(II)- and Zn(II)-ternary chelates with PhA have square planar geometrical structures. Thermal behaviour of the complexes is extensively studied using TG and DTA techniques. TG results show that water molecules (hydrated and coordinated) and anions are removed in the first and second steps while Gly, PhA, Pir and Ten are decomposed in the next and subsequent steps. The pyrolyses of the chelates into different gases are observed in the DTA curves as exo- or endothermic peaks. Also, phase transition states are observed in some chelates. Different thermodynamic parameters are calculated using Coats-Redfern method and the results are interpreted.

Desarrollo y optimización de una jalea de piroxicam 0,5 % Development and optimization related to a 0.5 % Piroxican jelly

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Oscar García Pulpeiro

2009-12-01

Full Text Available Se desarrolló por primera vez en Cuba, una formulación de jalea de piroxicam al 0,5 %. Se tomó como referencia la composición de la formulación líder del mercado FELDENE GELâ, a la cual se le efectuaron algunas modificaciones. Se realizaron 4 experimentos en las evaluaciones preliminares que sirvieron de base para la etapa posterior de diseño y optimización de la formulación. Se aplicó un diseño de experimentos con mezcla, para lo cual se emplearon como variables independientes la concentración de Carbopol 940, trietanolamina y hidroxipropilmetilcelulosa. Se evaluó la influencia de estos componentes en el pH, el área de extensibilidad y en algunas propiedades organolépticas. A partir de estos resultados, se seleccionó una formulación óptima.For the first time in Cuba a 0.5 % Piroxican jelly formula was developed. The point of reference was the leader formula from FELEDENE GELâ; market which underwent some modifications. During first assessments four experiments were carried out as basis for the later stage of formula design and optimization. An experimental design with mixture was applied using as independent variables the concentration of Carbopol 940, Trietanolamine, and Hidroxypropyl methylcellulose. Influence of these components on pH, the extensibility area, and on some organoleptic properties. From these results, an optimal formula was selected.

Ethyl cellulose nanoparticles as a platform to decrease ulcerogenic potential of piroxicam: formulation and in vitro/in vivo evaluation.

Science.gov (United States)

El-Habashy, Salma E; Allam, Ahmed N; El-Kamel, Amal H

2016-01-01

Nanoparticles (NPs) have long gained significant interest for their use in various drug formulations in order to increase bioavailability, prolong drug release, and decrease side effects of highly toxic drugs. The objective of this investigation was to evaluate the potential of ethyl cellulose-based NPs (EC-NPs) to modulate the release and reduce ulcerogenicity of piroxicam (PX) after oral administration. PX-loaded EC-NPs were prepared by solvent evaporation technique using different stabilizers at three concentration levels. Morphological examination of selected formulas confirmed the formation of spherical NPs with slightly porous surface. Formulation containing poloxamer-stabilized EC-NPs (P188/0.2), having a particle size of 240.26±29.24 nm, polydispersity index of 0.562±0.030, entrapment efficiency of 85.29%±1.57%, and modulated release of PX (88% after 12 hours), was selected as the optimum formulation. Differential scanning calorimetry demonstrated the presence of PX in an amorphous form in the NPs. Fourier-transform infrared spectroscopy revealed the possible formation of hydrogen bond and the absence of chemical interaction. In vivo study, evaluation of pharmacokinetic parameters, evaluation of gastric irritation potential, and histological examination were conducted after administration of the selected formulation. Time to reach maximum plasma concentration, t max, of poloxamer-stabilized EC-NPs was significantly higher than that of Feldene(®) 20 mg capsules (P≤0.001). Encapsulation of the acidic, gastric offender PX into NPs managed to significantly suppress gastric ulceration potential in rats (P≤0.05) as compared to that of PX suspension. A reduction of 66% in mean ulcer index was observed. In conclusion, poloxamer-stabilized EC-NPs (P188/0.2) had a significant potential of offsetting deleterious side effects common in PX use.

Effects of ibuprofen, diclofenac, naproxen, and piroxicam on the course of pregnancy and pregnancy outcome: a prospective cohort study

Science.gov (United States)

Nezvalová-Henriksen, K; Spigset, O; Nordeng, H

2013-01-01

Objective To investigate the individual effects of ibuprofen, diclofenac, naproxen, and piroxicam on pregnancy outcome. Design Cohort study. Setting Norwegian population. Population Total of 90 417 women and singleton child pairs. Methods Norwegian Mother and Child Cohort Study and Medical Birth Registry of Norway datasets were used. Main outcome measures Infant survival, congenital malformations, structural heart defects, neonatal complications, haemorrhage during pregnancy and postpartum, asthma at age of 18 months. Results One or more of the four NSAIDs were used by 6511 pregnant women, (7.2%). No effect on infant survival, congenital malformation, or structural heart defect rate was found. Second trimester ibuprofen use was significantly associated with low birth weight (adjusted OR 1.7, 95% CI 1.3 to 2.3) and second and third trimester use was significantly associated with asthma in the 18 month old child (adjusted OR 1.5, 95%CI 1.2 to 1.9 and adjusted OR 1.5, 95%CI 1.1 to 2.1). Second trimester diclofenac use was significantly associated with low birth weight (adjusted OR 3.1, 95% CI 1.1 to 9.0), whereas third trimester use was significantly associated with maternal vaginal bleeding (adjusted OR 1.8, 95% CI 1.1 to 3.0). No associations with other neonatal complications were found. Conclusions The lack of associations with congenital malformations is reassuring. The significant association between diclofenac and ibuprofen use late in pregnancy and maternal bleeding and asthma in the child respectively is consistent with their pharmacological effects. The increased risk of low birth weight may partly have been caused by underlying inflammatory conditions and was reassuringly similar to the expected baseline risk of low birth weight. PMID:23489333

The effect of non-steroidal anti-inflammatory drugs on the metabolism of /sup 14/C-arachidonic acid by human gingival tissue in vitro

Energy Technology Data Exchange (ETDEWEB)

Elattar, T.M.; Lin, H.S.; Tira, D.E.

1983-09-01

We investigated the effect of non-steroidal anti-inflammatory drugs on prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid (12-HETE) formation by inflamed human gingival tissues. Gingival tissue homogenates were incubated with /sup 14/C-arachidonic acid in the presence of indomethacin, piroxicam, or ibuprofen, and the organic solvent extracts were chromatographed on silica gel plates with standards for radiometric assay. There was a significant negative trend between the doses (10(-7)-10(-3) M) of each of indomethacin, piroxicam, and ibuprofen, and the amounts of PGF2 alpha, PGE2, PGD2, and 15-keto-PGE2 produced. All three drugs have a significant inhibitory effect on PGs and 12-HETE production at 10(-3) M when compared with the control. The rank order effectiveness of the drugs, at 10(-3) M, on PG inhibition was indomethacin greater than piroxicam greater than ibuprofen, and on 12-HETE inhibition was indomethacin greater than ibuprofen greater than piroxicam.

The effect of non-steroidal anti-inflammatory drugs on the metabolism of 14C-arachidonic acid by human gingival tissue in vitro

International Nuclear Information System (INIS)

Elattar, T.M.; Lin, H.S.; Tira, D.E.

1983-01-01

We investigated the effect of non-steroidal anti-inflammatory drugs on prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid (12-HETE) formation by inflamed human gingival tissues. Gingival tissue homogenates were incubated with 14 C-arachidonic acid in the presence of indomethacin, piroxicam, or ibuprofen, and the organic solvent extracts were chromatographed on silica gel plates with standards for radiometric assay. There was a significant negative trend between the doses (10(-7)-10(-3) M) of each of indomethacin, piroxicam, and ibuprofen, and the amounts of PGF2 alpha, PGE2, PGD2, and 15-keto-PGE2 produced. All three drugs have a significant inhibitory effect on PGs and 12-HETE production at 10(-3) M when compared with the control. The rank order effectiveness of the drugs, at 10(-3) M, on PG inhibition was indomethacin greater than piroxicam greater than ibuprofen, and on 12-HETE inhibition was indomethacin greater than ibuprofen greater than piroxicam

The relevance of piroxicam for the prevention and treatment of nonmelanoma skin cancer and its precursors

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Campione E

2015-10-01

Full Text Available Elena Campione,1 Evelin Jasmine Paternò,2 Eleonora Candi,3,4 Mattia Falconi,5 Gaetana Costanza,2 Laura Diluvio,1 Alessandro Terrinoni,4 Luca Bianchi,1 Augusto Orlandi2,6,7 1Department of Dermatology, 2Department of Biomedicine and Prevention, 3Department of Experimental Medicine and Surgery, University of Rome “Tor Vergata”, 4Biochemistry Laboratory IDI-IRCCS, Faculty of Medicine, University of Rome “Tor Vergata”, 5Department of Biology, University of Rome “Tor Vergata”, 6Institute of Anatomic Pathology, University of Rome “Tor Vergata”, 7Tor Vergata University-Policlinic of Rome, Rome, Italy Abstract: Piroxicam (PXM, a nonsteroidal anti-inflammatory drug, is an enolic benzothiazine and a potent member of the oxicam series. The drug suppresses the synthesis of proinflammatory enzymes, such as cyclooxygenases-1 and -2 (COX-1 and 2, downregulates the production of prostaglandins (PGs and tromboxanes, and inhibits polyamines production by blocking ornithine decarboxylase induction involved in nonmelanoma skin carcinogenesis. In addition, PXM is able to induce tumor cell apoptosis and suppresses metalloproteinase 2 activities. Skin carcinogenesis is a multistep process in which the accumulation of genetic events leads to a gradually dysplastic cellular expression, deregulation of cell growth, and carcinomatous progression. COX-1 upregulation plays a significant role in PG and vascular epidermal growth factor production supporting tumor growth. Increased level of PGs in premalignant and/or malignant cutaneous tumors is also favored by upregulation of COX-2 and downregulation of the tumor suppressor gene 15-hydroxy-prostaglandin dehydrogenase. Chemoprevention can be a hopeful approach to inhibit carcinoma occurrence before an invasive tumor develops. The chemopreventive effect of nonsteroidal anti-inflammatory drugs on nonmelanoma skin cancers has been established. In this study, we highlighted the different modalities of action

Influence of storage conditions on the physical and release ...

African Journals Online (AJOL)

This study investigated the effect of storage conditions on physical and release properties of lipophilic-based piroxicam suppositories with a view to determining the most desirable conditions for their storage. Piroxicam 20 mg suppositories were prepared by fusion method using cocoa butter, Witepsol H15® and Witepsol ...

Pectin/zein hydrogels for the delivery of drugs and nutrients

Science.gov (United States)

Two pectin/zein coacervates were prepared with either calcium ions or zinc ions. Piroxicam, a non-steroidal anti-inflammatory drug, was encapsulated. It was found that at lower solution pH the release of piroxicam displayed a near zero order kinetics, whether the coacervates were cross-linked with c...

Randomized comparison of effectiveness of unimodal opioid analgesia with multimodal analgesia in post–cesarean section pain management

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Adeniji AO

2013-05-01

Full Text Available Adetunji Oladeni Adeniji,1 Oluseyi Olaboyede A Atanda21Department of Obstetrics and Gynaecology, Ladoke Akintola University of Technology, Ogbomoso, Nigeria; 2Department of Obstetrics and Gynaecology, Ladoke Akintola University of Technology Teaching Hospital, Osogbo, NigeriaBackground: Postoperative pain leads to patient discomfort, decreased level of satisfaction, prolonged recovery, and higher health costs. Acute pain control therefore improves the overall quality of life in patients undergoing cesarean section. Pain relief is a fundamental human right, but there is no gold standard for post–cesarean section pain management.Objective: To compare the efficacy of pentazocine and tramadol used in unimodal and multimodal (in combination with piroxicam approach, in the management of post–cesarean section pain.Materials and methods: This study employed a random allocation design to compare the effectiveness of intramuscular pentazocine (60 mg or tramadol (100 mg as single analgesic agent and in combination with daily intramuscular piroxicam 20 mg, for the management of post–cesarean section pain during the immediate 12 hours after surgery. The primary outcome measure was control of postoperative pain, while the secondary outcome measures were the analgesic agent onset of action, duration of action, patient satisfaction, and maternal and neonatal adverse outcomes. Data obtained were entered into a predesigned sheet and analyzed with the Statistical Package for Social Sciences version 17. Means ± standard deviation (SD were calculated for the quantitative variables, and the difference between two independent groups was compared using unpaired Student's t-test. The level of significance was set at 0.05.Results: A total of 120 patients were equally and randomly allocated to four study groups – two that received unimodal analgesia (the pentazocine group and the tramadol group and two that received multimodal analgesia (the pentazocine-piroxicam

Ethyl cellulose nanoparticles as a platform to decrease ulcerogenic potential of piroxicam: formulation and in vitro/in vivo evaluation

Directory of Open Access Journals (Sweden)

El-Habashy SE

2016-05-01

Full Text Available Salma E El-Habashy, Ahmed N Allam, Amal H El-Kamel Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt Abstract: Nanoparticles (NPs have long gained significant interest for their use in various drug formulations in order to increase bioavailability, prolong drug release, and decrease side effects of highly toxic drugs. The objective of this investigation was to evaluate the potential of ethyl cellulose-based NPs (EC-NPs to modulate the release and reduce ulcerogenicity of piroxicam (PX after oral administration. PX-loaded EC-NPs were prepared by solvent evaporation technique using different stabilizers at three concentration levels. Morphological examination of selected formulas confirmed the formation of spherical NPs with slightly porous surface. Formulation containing poloxamer-stabilized EC-NPs (P188/0.2, having a particle size of 240.26±29.24 nm, polydispersity index of 0.562±0.030, entrapment efficiency of 85.29%±1.57%, and modulated release of PX (88% after 12 hours, was selected as the optimum formulation. Differential scanning calorimetry demonstrated the presence of PX in an amorphous form in the NPs. Fourier-transform infrared spectroscopy revealed the possible formation of hydrogen bond and the absence of chemical interaction. In vivo study, evaluation of pharmacokinetic parameters, evaluation of gastric irritation potential, and histological examination were conducted after administration of the selected formulation. Time to reach maximum plasma concentration, tmax, of poloxamer-stabilized EC-NPs was significantly higher than that of Feldene® 20 mg capsules (P≤0.001. Encapsulation of the acidic, gastric offender PX into NPs managed to significantly suppress gastric ulceration potential in rats (P≤0.05 as compared to that of PX suspension. A reduction of 66% in mean ulcer index was observed. In conclusion, poloxamer-stabilized EC-NPs (P188/0.2 had a significant potential of

Efficacy of a film-forming medical device containing sunscreen (50+) and piroxicam 0.8% in actinic keratosis and field cancerization: a multicenter, assessor-blinded, 3 month trial.

Science.gov (United States)

Puviani, Mario; Galloni, Chiara; Marchetti, Silvia; Sergio Pavone, Paolo; Lovati, Silvia; Pistone, Giuseppe; Caputo, Valentina; Tilotta, Giovanna; Scarcella, Giuseppe; Campione, Elena; Diluvio, Laura; Garofalo, Virginia; Bianchi, Luca; Milani, Massimo

2017-07-01

Sunscreen protection in subjects with actinic keratosis (AK) is highly recommended to prevent clinical evolution of this in situ skin cancer condition. Use of topical anti-cyclooxygenase drugs such as diclofenac and piroxicam reduces the number of lesions and improves the cancerization field. A film-forming medical device in a cream formulation containing organic and inorganic sun-filters (50+ SPF) and piroxicam 0.8% (ACTX) has shown in a pilot, single-center, open trial to reduce AK lesions improving the cancerization field. We evaluated in a multicenter, assessor-blinded, 3 month trial the efficacy of ACTX in AK. A total of 70 subjects with at least three AK lesions on the scalp or face were enrolled after written informed consent. Primary outcomes of the study were the clinical evolution of number of AK lesions on a target zone area and the evolution of dermoscopy features of the target lesion, assessing erythema, scaling, pigmentation, and follicular plug, using a 5 point score (from 0 to 4; maximum score: 16). Lesion count and dermoscopy score were evaluated in a blind fashion assessing digital color high definition coded images. A secondary outcome was the Investigator Global Score (IGS) of clinical evolution of the target area using a 7 point scale from -2 (significantly worse) to +4 (completely cured). IGS was evaluated in an open fashion. Subjects were instructed to apply the cream twice daily on the target area, using one finger-tip unit for the treatment of a 35 cm 2 area. All but one subject (40 men and 30 women, mean age 73 years) concluded the study period. At baseline the mean (±SD) number of AK lesions in the target area were 7.0 (5.9) with a median value of 5 and the dermoscopy score of the target lesion was 7.0 (2.3) with a median value of 7.0. ACTX treatment reduced AK lesions to 3.2 (2.9), (p = .0001; Wilcoxon Test), representing a 55% relative reduction. Dermoscopy score was reduced to 3.3 (2.6) (p = .0001) (a reduction of 53%). The

Anti-inflammatory activity of silymarin in patients with knee osteoarthritis

International Nuclear Information System (INIS)

Hussain, Saad A.; Numan, Intesar T.; Al-Khalifa, Ihab I.; Jassim, Nizar A.; Abdullah, Talal A.

2009-01-01

Objective was to evaluate the anti-inflammatory effect of Silymarin in patients with knee osteoarthritis (OA) in comparison with piroxicam and meloxicam. A double-blind clinical trial was performed at the Department of Rheumatology, Baghdad Teaching Hospital, Iraq during the period from October 2004 to September 2005, in which 220 patients (79 males and 141 females) with painful knee osteoarthritis were randomized into 5 groups, treated with either silymarin (300mg/day), piroxicam (20mg/day), meloxicam (15mg) or a combination of silymarin with piroxicam or meloxicam. Serum levels of interleukin-1 alpha, interleukin-8 and the complement proteins C3 and C4 were assessed at zero time and after 8 weeks. Silymarin reduces significantly serum levels of IL-1 alpha and IL-8, C3 and C4 after 8 weeks compared to the pre-treatment levels, while IL-8 decreased significantly, compared to pre-treatment value. Meloxicam elevates serum levels of IL-1 alpha significantly, IL-8 did not significantly change compared to the pre-treatment value. Piroxicam or meloxicam produced slight, non-significant increase in serum levels of complement proteins after the 8-week treatment period. Adjunct use of silymarin with piroxicam results in significant reduction in both cytokines (IL-1 alpha and IL-8) and serum levels of C3 and C4. However, its adjunct use with, meloxicam did not reveal any significant changes in this respect. Silymarin reduces the elevated levels of interleukins and complement proteins, when used alone, or in combination with NSAIDs for treatment of knee OA. (author)

radiolabeling of some antiinflammatory agents for inflammation localization

International Nuclear Information System (INIS)

Taha, A.M.A.A.

2004-01-01

this work has been carried out to investigate the labeling of pefloxacin. piroxicam with technetium -99 m and indomethacine with iodine-125 . the labeling techniques are effective. as a high labeling yield (98%) was obtained. depending on the data obtained. 99m Tc-pefloxacin shows good differentiation between septic and sterile inflammation . piroxicam was labeled effectively with technetium -99 m due to the presence of electrons donating atoms in its structure such as sulfur- nitrogen -oxygen . the labeling reaction proceeds well at room temperature. 99m Tc-piroxicam shows good localization in inflamed foci at 24 h post injection. indomethacin was successfully labeled with iodine -125 via electrophilic substitution . 125 I-indomethacin was found stable in -vivo as the thyroid gland uptake not exceeds 2% . labeled indomethacin shows a good localization in inflamed muscle either septic or sterile

Oxidant-stimulated chloride secretion in rat jejunum in vitro is mediated by eicosanoids

DEFF Research Database (Denmark)

Bertelsen, L.S.; Bukhave, Klaus

2003-01-01

Specific effects of the cytotoxic secondary lipid oxidation product, 4- hydroxynonenal (10(-8) - 10(-4) M), on intact sheets of rat jejunum were measured as changes in short circuit current (DeltaI(sc)) following cumulative addition to either the mucosal or serosal side, using the analogous...... (4- hydroxynonenal: 88.9 +/- 3.0%, N = 6, p piroxicam (10 μM), while 4......- hydroxynonenal- induced &UDelta;I-sc, was abolished by piroxicam (N = 8, P

Synthesis, investigation and spectroscopic characterization of piroxicam ternary complexes of Fe(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) with glycine and DL-phenylalanine

Science.gov (United States)

Mohamed, Gehad G.; El-Gamel, Nadia E. A.

2004-11-01

The ternary piroxicam (Pir; 4-hydroxy-2-methyl- N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide) complexes of Fe(II), Fe(III), Co(II), Ni(II), Cu(II) and Zn(II) with various amino acids (AA) such as glycine (Gly) or DL-phenylalanine (PhA) were prepared and characterized by elemental analyses, molar conductance, IR, UV-Vis, magnetic moment, diffuse reflectance and X-ray powder diffraction. The UV-Vis spectra of Pir and the effect of metal chelation on the different interligand transitions are discussed in detailed manner. IR and UV-Vis spectra confirm that Pir behaves as a neutral bidentate ligand coordinated to the metal ions via the pyridine- N and carbonyl group of the amide moiety. Gly molecule acted as a uninegatively monodentate ligand and coordinate to the metal ions through its carboxylic group, in addition PhA acted as a uninegatively bidentate ligand and coordinate to the metal ions through its carboxylic and amino groups. All the chelates have octahedral geometrical structures while Cu(II)- and Zn(II)-ternary chelates with PhA have square planar geometrical structures. The molar conductance data reveal that most of these chelates are non electrolytes, while Fe(III)-Pir-Gly, Co(II)-, Ni(II)-, Cu(II)- and Zn(II)-Pir-PhA cheletes were 1:1 electrolytes. X-ray powder diffraction is used as a new tool to estimate the crystallinity of chelates as well as to elucidate their geometrical structures.

Topical Effects of Artemisia Absinthium Ointment and Liniment in Comparison with Piroxicam Gel in Patients with Knee Joint Osteoarthritis: A Randomized Double-Blind Controlled Trial.

Science.gov (United States)

Basiri, Zahra; Zeraati, Fatemeh; Esna-Ashari, Farzaneh; Mohammadi, Farshid; Razzaghi, Keyvan; Araghchian, Malihe; Moradkhani, Shirin

2017-11-01

Pain alleviation and improvement of functional status are the main objectives in the treatment of osteoarthritis. Artemisia absinthium (AA) was used traditionally in reducing pain and inflammation. The aim of the present study was to compare the effects of topical formulations of AA and piroxicam gel (PG) among patients with knee osteoarthritis. In total, 90 outpatients aged 30-70 years with the diagnosis of primary osteoarthritis in at least one knee were enrolled in a randomized double-blind clinical trial. The patients referred to the Rheumatology Clinic at Shahid Beheshti Hospital in Hamadan province during 2012-2013. The patients were randomly assigned into three groups, 30 patients per group, and respectively received AA ointment (AAO) 3%, AA liniment (AAL) 3%, and PG; three times daily (TID) for 4 weeks. The patients were visited at baseline, week 4, and week 6. The effectiveness criteria were pain severity which was assessed with a 10-point visual analog scale (VAS), the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) for total pain score (WTPS), total physical function score (WTPFS), and total stiffness score (WTSS). Repeated measure ANOVA, paired t test and post hoc were used to compare variables. Statistical analysis was performed using the SPSS software, version 13.0 (SPSS Inc., Chicago, Illinois). All groups had similar patient demographics. The administration of PG significantly improved all tested criteria with no recurrence after discontinuing the treatment protocol. AAO alleviated all tested factors except for WTSS. Alleviation was comparable to PG. AAL only reduced pain factors (VAS, WTPS) in week 4 with recurrence in week 6. Administration of Artemisia ointment may have beneficial effects in the treatment of osteoarthritis. Trial Registration Number: IRCT201202123109N3.

Peginterferon Alfa-2b Injection (Sylatron)

Science.gov (United States)

... Naprosyn), ondansetron (Zofran), paroxetine (Paxil, Pexeva), phenytoin (Dilantin), piroxicam (Feldene), propafenone (Rhythmol), risperidone (Risperdal), rosiglitazone (Avandia), sulfamethoxazole ( ...

Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils

Directory of Open Access Journals (Sweden)

Paino I.M.M.

2005-01-01

Full Text Available The release of reactive oxygen specie (ROS by activated neutrophil is involved in both the antimicrobial and deleterious effects in chronic inflammation. The objective of the present investigation was to determine the effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs (NSAIDs on the production of ROS by stimulated rat neutrophils. Diclofenac (3.6 µM, indomethacin (12 µM, naproxen (160 µM, piroxicam (13 µM, and tenoxicam (30 µM were incubated at 37ºC in PBS (10 mM, pH 7.4, for 30 min with rat neutrophils (1 x 10(6 cells/ml stimulated by phorbol-12-myristate-13-acetate (100 nM. The ROS production was measured by luminol and lucigenin-dependent chemiluminescence. Except for naproxen, NSAIDs reduced ROS production: 58 ± 2% diclofenac, 90 ± 2% indomethacin, 33 ± 3% piroxicam, and 45 ± 6% tenoxicam (N = 6. For the lucigenin assay, naproxen, piroxicam and tenoxicam were ineffective. For indomethacin the inhibition was 52 ± 5% and diclofenac showed amplification in the light emission of 181 ± 60% (N = 6. Using the myeloperoxidase (MPO/H2O2/luminol system, the effects of NSAIDs on MPO activity were also screened. We found that NSAIDs inhibited both the peroxidation and chlorinating activity of MPO as follows: diclofenac (36 ± 10, 45 ± 3%, indomethacin (97 ± 2, 100 ± 1%, naproxen (56 ± 8, 76 ± 3%, piroxicam (77 ± 5, 99 ± 1%, and tenoxicam (90 ± 2, 100 ± 1%, respectively (N = 3. These results show that therapeutic levels of NSAIDs are able to suppress the oxygen-dependent antimicrobial or oxidative functions of neutrophils by inhibiting the generation of hypochlorous acid.

77 FR 74669 - Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence...

Science.gov (United States)

2012-12-17

... Phenoxybenzamine hydrochloride Q Quinine sulfate R Risedronate sodium T Tacrolimus Thalidomide Tinidazole For a... Gabapentin P Piroxicam S Sodium Phosphate, dibasic, anhydrous; sodium phosphate, monobasic, monohydrate [[Page 74670

Development of Protective Agent Against Sulfur Mustard-Induced Skin Lesions

National Research Council Canada - National Science Library

Wormser, Uri

2002-01-01

.... Incorporation of the antiinflammatory drug piroxicam and the steroidal antiinflamamtory agent clobetasol, caused the formulation to protect at intervals of 45 and 60 rain in the mouse ear swelling...

Biodegradation and kinetics of organic compounds and heavy metals in an artificial wetland system (AWS) by using water hyacinths as a biological filter.

Science.gov (United States)

Rodríguez-Espinosa, P F; Mendoza-Pérez, J A; Tabla-Hernandez, J; Martínez-Tavera, E; Monroy-Mendieta, M M

2018-01-02

The objective of the present study was to investigate the ability of water hyacinth (Eichhornia crassipes) to absorb organic compounds (potassium hydrogen phthalate, sodium tartrate, malathion, 2,4-dichlorophenoxy acetic acid (2,4-D), and piroxicam). For the aforementioned purpose, an artificial wetland system (AWS) was constructed and filled with water hyacinth collected from the Valsequillo Reservoir, Puebla, Mexico. Potassium hydrogen phthalate and sodium tartrate were measured in terms of chemical oxygen demand (COD) and biological oxygen demand (BOD). The present study indicated that the water hyacinths absorbed nearly 1.8-16.6 g of COD kg -1 dm (dry mass of water hyacinth), while the absorbance efficiency of BOD was observed to be 45.8%. The results also indicated that the maximum absorbance efficiency of malathion, 2,4-D, and piroxicam was observed to be 67.6%, 58.3%, and 99.1%, respectively. The kinetics of organic compounds fitted different orders as malathion followed a zeroth-order reaction, while 2,4-D and piroxicam followed the first-order reactions. Preliminary assessment of absorption of heavy metals by the water hyacinth in the AWS was observed to be (all values in mg g -1 ) 7 (Ni), 13.4 (Cd), 16.3 (Pb), and 17.5 (Zn) of dry biomass, thus proving its feasibility to depurate wastewater.

Study of Osteoarthritis Treatment with Anti-Inflammatory Drugs: Cyclooxygenase-2 Inhibitor and Steroids

Directory of Open Access Journals (Sweden)

Hongsik Cho

2015-01-01

Full Text Available Patients with osteoarthritis (OA, a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs, and cyclooxygenase-2 (COX-2 selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM. To compare the effects of these treatments on chondrocyte metabolism, TNF-α was incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2. The chondrocytes were then treated with either a steroid (prednisone, a nonspecific COX inhibitor NSAID (piroxicam, or a COX-2 selective NSAID (celecoxib. Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxib in vivo was investigated using a posttraumatic OA (PTOA mouse model. In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 production in vitro and that celecoxib may demonstrate beneficial effects on anabolic metabolism in vivo.

Original Research

African Journals Online (AJOL)

home

2014-03-17

Mar 17, 2014 ... solid dispersion technique presents a challenge to the formulation scientists ... dispersed drug was prepared from polyvinyl pyrrolidone (PVP) (pharmaceutical grade), a .... methanolic HCl to obtain a solution with the piroxicam.

Development of Protective Agent Against Sulfur Mustard-Induced Skin Lesions

National Research Council Canada - National Science Library

Wormser, Uri

2001-01-01

The present study is a continuation of two years project. During the third year of project we improved the iodine formulation by incorporating the antiinflammatory drug piroxicam and the anti H1 receptor diphehydramine...

Nigerian Quarterly Journal of Hospital Medicine - Vol 8, No 2 (1998)

African Journals Online (AJOL)

1995) · EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT ... study of the efficacy and safety of tenoxicam vs. Piroxicam in extra - articular inflammatory conditions · EMAIL FULL TEXT EMAIL FULL TEXT

Rhizomes of Eremostachys laciniata: Isolation and Structure Elucidation of Chemical Constituents and a Clinical Trial on Inflammatory Diseases

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Abbas Delazar

2013-08-01

Full Text Available Purpose: The purpose of this study was the isolation and structure elucidation of chemical compounds from the rhizomes of Eremostachys laciniata (L Bunge (EL, an Iranian traditional medicinal herb with a thick root and pale purple or white flowers as well as the clinical studies on the therapeutic efficacy and safety of topical application of the EL extract in the management of some inflammatory conditions, e.g., arthritis, rheumatoid arthritis and septic arthritis (Riter’s syndrome. Methods: The structures of the isolated compounds were elucidated unequivocally on the basis of one and two dimensional NMR, UV and HR-FABMS spectroscopic data analyses. A single-blinded randomized clinical trial was carried out with the extract of the rhizomes of E. laciniata (EL to determine the efficacy and safety of the traditional uses of EL compared to that of piroxicam in treatment of inflammatory diseases, e.g., osteoarthritis, rheumatoid arthritis and Reiter’s syndrome. Results: Eleven iridoid glycosides, two phenylethanoids and two phytosterols were isolated and identified for the first time from the rhizomes of EL. After 14 days of treatment with the EL and piroxicam ointments, all groups showed significant improvements compared to the control groups. EL (5% ointment induced better initial therapeutic response than piroxicam (5% onitment. Conclusion: This clinical trial established that EL was suitable for topical applications as a safe and effective complementary therapy for inflammatory diseases.

The effect of balanced analgesia on early convalescence after major orthopaedic surgery

DEFF Research Database (Denmark)

Møiniche, S; Hjortsø, N C; Hansen, B L

1994-01-01

Forty-two patients scheduled for total knee arthroplasty (n = 20) or hip arthroplasty (n = 22) were randomly allocated to receive either continuous epidural bupivacaine/morphine for 48 h postoperatively plus oral piroxicam, or general anaesthesia followed by a conventional intramuscular opioid...

Prevention of postoperative pain by balanced analgesia

DEFF Research Database (Denmark)

Dahl, J B; Rosenberg, J; Dirkes, W E

1990-01-01

Fourteen patients undergoing colorectal surgery received an intraoperative afferent neural block with combined intrathecal and extradural local anaesthetics plus a balanced postoperative low-dose regimen of extradural bupivacaine 10 mg h-1-morphine 0.2 mg h-1 and systemic piroxicam 20 mg/24 h...

Drug-drug interaction may explain failed antibiotic effectiveness - an ...

African Journals Online (AJOL)

The in vivo effect of co-administration of the NSAIDs (acetyl salicylic acid (ASA), piroxicam, indomethacin and paracetamol) with ciprofloxacin against Staphylococcus aureus in Swiss mice, rendered neutropenic by pre-treatment with cyclophosphamide, was evaluated using animal model. Using the murine thigh model, ...

Complementing high-throughput X-ray powder diffraction data with quantum-chemical calculations

DEFF Research Database (Denmark)

Naelapaa, Kaisa; van de Streek, Jacco; Rantanen, Jukka

2012-01-01

of piroxicam form III. These combined experimental/quantum-chemical methods can provide access to reliable structural information in the course of an intensive experimentally based solid-form screening activity or in other circumstances wherein single crystals might never be viable, for example, for polymorphs...

Characterization of Growth Hormone Resistance in Experimental and Ulcerative Colitis

DEFF Research Database (Denmark)

Soendergaard, Christoffer; Kvist, Peter Helding; Thygesen, Peter

2017-01-01

in this condition are unclear. In situ hybridization targeting the GH receptor (GHR) and relevant transcriptional analyses were performed in patients with UC and in IL-10 knock-out mice with piroxicam accelerated colitis (PAC). Using cultured primary epithelial cells, the effects of inflammation on the molecular...

Toxic effects of non-steroidal anti-inflammatory agents in rats ...

African Journals Online (AJOL)

The toxicosis of some non-steroidal anti-inflammatory drugs, piroxicam, indomethacin, phenylbutazone, and aspirin, which occasionally are locally used in Nigeria as rodenticides have been evaluated in rats using changes in the serum biochemical and haematological parameters as indices of toxicity. In the study, no ...

Author Details

African Journals Online (AJOL)

Nnamani, PO. Vol 8, No 1 (2010) - Articles Piroxicam-Loaded P90gylated Tallow Fat-Based Solid Lipid Microparticles: Characterization and in Vivo Evaluation Abstract · Vol 8, No 1 (2010) - Articles New Approach to Solid Lipid Microparticles USING Biocompatible Homolipids-Templated Heterolipid Micricarriers for ...

Characterics of exposure to non-steroid anti-inflammatory drugs in European databases.

NARCIS (Netherlands)

Vries, F. de; Kieler, H.; Dijk, L. van; Svensson, T.; Staa, T. van

2010-01-01

Background: A systematic review reported that users of naproxen, ibuprofen and piroxicam did not have an increased risk of myorcardial infarction (MI), whilst users of diclofenac and indomethacin showed significantly increased risk of MI (RRs 1.4 and 1.3). While there may be biological plausible

A step toward development of printable dosage forms for poorly soluble drugs

DEFF Research Database (Denmark)

Raijada, Dharaben Kaushikkumar; Genina, Natalja; Fors, Daniela

2013-01-01

The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkjet...

PENGENDALIAN PERSEDIAAN BAHAN BAKU OBAT DENGAN MENGGUNAKAN METODE EOQ PROBABILISTIK BERDASARKAN PERAMALAN EXPONENTIAL SMOOTHING PADA PT. XYZ

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Fila Dristiana

2015-10-01

Full Text Available PT. XYZ is one of the manufactures of parmacheutical. Problems which often appeared are surplus and shortage material. Inventory material control not optimum because order only esimate. With exponential smoothing method can be devise of demand next period and EOQ Probabilistic for to know economic order quantity, total safety stock and reorder point so can minimization inventory cost. Purpose of research are to know exponential smoothing method what representatif for manufacture and give recomendation of this research. Results of research are exponential smoothing method representatif for manufacture and EOQ probabilistic method for Antalgin, Paracetamol and Piroxicam material are economic order quantity in the amount of 313 kg, 928 kg and 33 kg, safety stock 160 kg, 403 kg and 2kg and reorder point 325 kg, 1080 kg dan 14 kg. So total inventory cost of Antalgin, Paracetamol and Piroxicam material in the amount of Rp.3.847.146, Rp.5.025.081 and Rp.1.932.255.

ACTION OF CHEMICALLY DIFFERENT PROSTAGLANDIN BLOCKERS ON THE ADRENAL HORMONES IN PIGEONS DURING STRESS.

Science.gov (United States)

Sarkar, S; Ghosh, S; Sengupta, S; Dasadhikari, S; Ghosh, A

1999-01-01

The effect of prostaglandin (PG) inhibitors differing in their chemical nature, viz. Aspirin (acetylsalicylic acid), Mefenamic acid (fenamates), Diclofenac (phenylacetic acid derivative) and Piroxicam (oxicam derivative) on the adrenal hormones was studied in acutely stressed pigeons. None of these PG blockers exerted any significant effect on the catecholamine and corticosterone content of the control, i.e. unstressed pigeon adrenal gland excepting mefenamic acid which caused a release of epinephrine. Aspirin, diclofenac and piroxicam did not modulate the catecholamine or corticosterone secretion whereas mefenamic acid caused a released of both epinephrine and norepinephrine and increased the adrenal corticosterone content in the acutely stressed pigeons. These results were compared with those obtained from studies on the effects of other chemically different PG blockers, indomethacin (a methylated indole derivative) and ibuprofen (a propionic acid derivative). It is suggested that chemically and structurally different PG inhibitors show diverse action in the same species under similar stress conditions.

Browse Title Index

African Journals Online (AJOL)

Items 151 - 200 of 246 ... Vol 14, No 1 (2017), Influence of storage conditions on the physical and release properties of piroxicam suppositories formulated with lipophilic bases, Abstract. Francis A. Oladimeji ... Vol 6, No 1 (2009), Pharmacognostic profile and in vitro cytotoxic activity of Adenema hyssopifolium G. Don, Abstract.

The In Vivo Analgesic Activity of Aqueous and Ethanolic Extracts of ...

African Journals Online (AJOL)

The standard drug, Piroxicam also produced a significant (P < 0.05) reduction in writhings, producing pain inhibition of 70.3 %. Conclusions: The analgesic effects produced by crude extracts of both experimental plants confirm that they are endowed with analgesic properties. Further work is suggested to isolate active ...

Diseño y validación de un método espectrofotométrico para el control de calidad del piroxicam jalea 0,5 % Design and validation of a spectrophotometry method used in quality control of a 0,5 % Piroxican jelly

Directory of Open Access Journals (Sweden)

Yania Suárez Pérez

2009-12-01

Full Text Available La jalea de piroxicam al 0,5 % es un nuevo producto en fase de desarrollo de la Empresa Laboratorio "Roberto Escudero Díaz". En el presente trabajo se diseñó un método por espectrofotometría UV, para lo cual se empleó ácido clorhídrico etanólico como disolvente y 328 nm como longitud de onda de máxima absorción. Se estableció un procedimiento simple y rápido para procesar la muestra previa al análisis. Posteriormente se aplicó la validación de este según exigencias regulatorias actuales. El método resultó suficientemente específico, lineal, preciso y exacto en el rango de 3,125 a 9,375 µg/mL. Se aplicó a la cuantificación del principio activo en 3 lotes de la formulación desarrollada, con resultados satisfactorios sin diferencias estadísticamente significativas según el procesamiento aplicado.The 0.5 % jelly Piroxican is a new product in developing phase from "Roberto Escudero Díaz" Laboratory Enterprise. In present paper a UV spectrophotometry method was designed using ethanol chloride acid as solvent and 328 nm as maximal absorption wave length. A simple and fast procedure was established to processing the sample previous to analysis. Subsequently, we applied the validation of it according current regulatory demands. Method was enough specific, linear, precise and exact at the 3.125 to 9.375 µg/mL. Active principle quantification was applied in three batches of developed formula achieving satisfactory results without statistically significant differences according the applied procedure.

IL-33 promotes GATA-3 polarization of gut-derived T cells in experimental and ulcerative colitis

DEFF Research Database (Denmark)

Seidelin, Jakob Benedict; Coskun, Mehmet; Kvist, Peter Helding

2015-01-01

of the immune response in experimental colitis (piroxicam-accelerated colitis (PAC) in IL-10 -/- mice, dextran sodium sulfate (DSS) model) and UC.METHODS: Colonic IL-33 expression was determined in UC (8 active UC, 8 quiescent UC, and 7 controls) and experimental colitis. Mesenteric lymph node (MesLN) T cells...

In situ epicatechin-loaded hydrogel implants for local drug delivery ...

African Journals Online (AJOL)

In vivo anti-inflammatory activity was determined and compared with 2 % piroxicam gel as standard. Motor function activity in a rat model of spinal injury was examined comparatively with i.v. methylprednisolone as standard. Results: The N-methyl pyrrolidone solution (containing 1 % w/w epicatechin with 2 to 10 % w/w ...

Preventing Crystal Agglomeration of Pharmaceutical Crystals Using Temperature Cycling and a Novel Membrane Crystallization Procedure for Seed Crystal Generation

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Elena Simone

2018-01-01

Full Text Available In this work, a novel membrane crystallization system was used to crystallize micro-sized seeds of piroxicam monohydrate by reverse antisolvent addition. Membrane crystallization seeds were compared with seeds produced by conventional antisolvent addition and polymorphic transformation of a fine powdered sample of piroxicam form I in water. The membrane crystallization process allowed for a consistent production of pure monohydrate crystals with narrow size distribution and without significant agglomeration. The seeds were grown in 350 g of 20:80 w/w acetone-water mixture. Different seeding loads were tested and temperature cycling was applied in order to avoid agglomeration of the growing crystals during the process. Focused beam reflectance measurement (FBRM; and particle vision and measurement (PVM were used to monitor crystal growth; nucleation and agglomeration during the seeded experiments. Furthermore; Raman spectroscopy was used to monitor solute concentration and estimate the overall yield of the process. Membrane crystallization was proved to be the most convenient and consistent method to produce seeds of highly agglomerating compounds; which can be grown via cooling crystallization and temperature cycling.

The Phytochemical Constituents, Analgesic and Anti-inflammatory ...

African Journals Online (AJOL)

This effect was comparable to the observed effect with Piroxicam (0.5mg/kg) which was used as a standard. The effect was also dose- dependent. Furthermore, Jatropha ... This also supports its use traditionally as an anti-snake bite, rheumatism and anti- cancer or anti-tumor agent. Further study is on the way to find out the ...

Tautomerism and biological activity of beta-diketoner, triketoner, beta-ketoesters and beta-ketoamides. A mini review

DEFF Research Database (Denmark)

Hansen, Poul Erik

2017-01-01

The review deals with β-diketones, β-ketoester, β-ketoamides, triketones, their tautomerism and biological activity. In addition, it covers briefly methods to detect tautomerism in particular NMR and deuterium isotope effects on chemical shifts, both primary and secondary. A number of typical sys...... systems are treated such as: usnic acid, tetracyclines, piroxicam, curcurmines, humulones, acyltetramic acids and quinolone 3-esters....

Fixed Drug Eruptions (FDE) in an Urban Centre in South-South ...

African Journals Online (AJOL)

TNHJOURNALPH

Piroxicam. 1. 3.03. Naloxone. 1. 3.03. Ibuprofen. 1. 3.03. Buscopan. 1. 3.03. Ampiclox. 1. 3.03. Tetracycline. 1. 3.03. Quinine. 1. 3.03. Fixed drug eruptions most often involved the face and the lips in co-trimoxazole, with. 16(37.5%) patients affected, and a male preponderance of 9(56.25%). The only case of genital affectation ...

Randomized controlled trial about pain medication flupirtine ignores recent pharmacovigilance warnings

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Puljak L

2018-01-01

Full Text Available Livia Puljak1,2 1Laboratory for Pain Research, University of Split School of Medicine, Split, Croatia; 2Department for Development, Research and Health Technology Assessment, Agency for Quality and Accreditation in Health Care and Social Welfare, Zagreb, CroatiaOn October 16, 2017 in the Journal of Pain Research, a randomized controlled trial (RCT comparing efficacy and safety of flupirtine versus piroxicam in postoperative pain in patients undergoing lower limb surgery was published.1 However, this paper fails to report important information. Author’s reply Sowmya Chinnaiyan,1 Narayana Sarala,1 Heddur Shanthappa Arun21Department of Pharmacology, 2Department of Orthopedics, Sri Devaraj Urs Medical College, Sri Devaraj Urs Academy of Higher Education and Research, Kolar, Karnataka, India We thank Livia Puljak for the valuable insights on the article titled “A comparative study of efficacy and safety of flupirtine  versus piroxicam in postoperative pain in patients undergoing lower limb surgery” published in the Journal of Pain Research. The concerns highlighted in the Letter to the Editor have been answered.View the original paper by Chinnaiyan and colleagues. 

Concomitant monitoring of implant formation and drug release of in situ forming poly (lactide-co-glycolide acid) implants in a hydrogel matrix mimicking the subcutis using UV-vis imaging.

Science.gov (United States)

Sun, Yu; Jensen, Henrik; Petersen, Nickolaj J; Larsen, Susan W; Østergaard, Jesper

2018-02-20

For poly (lactide-co-glycolide acid) (PLGA)-based in situ forming implants, the rate of implant formation plays an important role in determining the overall drug release kinetics. Currently, in vitro techniques capable of characterizing the processes of drug release and implant formation at the same time are not available. A hydrogel-based in vitro experimental setup was recently developed requiring only microliter of formulation and forming a closed system potentially suitable for interfacing with various spectroscopic techniques. The aim of the present proof-of-concept study was to investigate the feasibility of concomitant UV imaging, Vis imaging and light microscopy for detailed characterization of the behavior of in situ forming PLGA implants in the hydrogel matrix mimicking the subcutis. The model compounds, piroxicam and α-lactalbumin were added to PLGA-1-methyl-2-pyrrolidinone and PLGA-triacetin solutions. Upon bringing the PLGA-solvent-compound pre-formulation in contact with the hydrogel, Vis imaging and light microscopy were applied to visualize the depot formation and UV imaging was used to quantify drug transport in the hydrogel. As compared to piroxicam, the α-lactalbumin invoked an acceleration of phase separation and an increase of implant size. α-Lactalbumin was released faster from the PLGA-1-methyl-2-pyrrolidinone system than the PLGA-triacetin system opposite to the piroxicam release pattern. A linear relationship between the rate of implant formation and initial compound release within the first 4h was established for the PLGA-NMP systems. This implies that phase separation may be one of the controlling factors in drug release. The rate of implant formation may be an important parameter for predicting and tailoring drug release. The approach combining UV imaging, Vis imaging and light microscopy may facilitate understanding of release processes and holds potential for becoming a useful tool in formulation development of in situ forming

Direct comparison of low- and mid-frequency Raman spectroscopy for quantitative solid-state pharmaceutical analysis.

Science.gov (United States)

Lipiäinen, Tiina; Fraser-Miller, Sara J; Gordon, Keith C; Strachan, Clare J

2018-02-05

This study considers the potential of low-frequency (terahertz) Raman spectroscopy in the quantitative analysis of ternary mixtures of solid-state forms. Direct comparison between low-frequency and mid-frequency spectral regions for quantitative analysis of crystal form mixtures, without confounding sampling and instrumental variations, is reported for the first time. Piroxicam was used as a model drug, and the low-frequency spectra of piroxicam forms β, α2 and monohydrate are presented for the first time. These forms show clear spectral differences in both the low- and mid-frequency regions. Both spectral regions provided quantitative models suitable for predicting the mixture compositions using partial least squares regression (PLSR), but the low-frequency data gave better models, based on lower errors of prediction (2.7, 3.1 and 3.2% root-mean-square errors of prediction [RMSEP] values for the β, α2 and monohydrate forms, respectively) than the mid-frequency data (6.3, 5.4 and 4.8%, for the β, α2 and monohydrate forms, respectively). The better performance of low-frequency Raman analysis was attributed to larger spectral differences between the solid-state forms, combined with a higher signal-to-noise ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

Screening and quantitative determination of twelve acidic and neutral pharmaceuticals in whole blood by liquid-liquid extraction and liquid chromatography-tandem mass spectrometry

DEFF Research Database (Denmark)

Simonsen, Kirsten Wiese; Steentoft, Anni; Buck, Maike

2010-01-01

. The method was fully validated for salicylic acid, paracetamol, phenobarbital, carisoprodol, meprobamate, topiramate, etodolac, chlorzoxazone, furosemide, ibuprofen, warfarin, and salicylamide. The method also tentatively includes thiopental, theophylline, piroxicam, naproxen, diclophenac, and modafinil......We describe a multi-method for simultaneous identification and quantification of 12 acidic and neutral compounds in whole blood. The method involves a simple liquid-liquid extraction, and the identification and quantification are performed using liquid chromatography-tandem mass spectrometry...

Método analítico para a determinação de meloxicam em plasma humano por cromatografia líquida de alta eficiência (CLAE Determination of meloxicam in human plasma by HPLC

Directory of Open Access Journals (Sweden)

Valentina Porta

2005-06-01

Full Text Available Desenvolveu-se e validou-se método analítico simples, rápido e específico para quantificação de meloxicam (inibidor da COX-2 em plasma humano através da cromatografia líquida de alta eficiência, para aplicação em estudos de bioequivalência. Piroxicam foi utilizado como padrão interno. Empregou-se cromatografia em fase reversa com coluna modelo Synergi RP-MAX (150 x 4,6 mm, à temperatura de 30 ºC e fase móvel constituída por mistura de acetonitrila e tampão fosfato 0,025 mol/L pH 4,5 (40:60, v/v, a um fluxo de 1,0 mL/min. Os analitos foram detectados por UV a 364 nm. As amostras de plasma foram acidificadas com ácido clorídrico 1 mol/L, extraídas utilizando-se éter terc-butil metílico e, após filtração e secagem, o resíduo foi reconstituído em 250 mL de fase móvel para injeção em CLAE. Os tempos de retenção para meloxicam (padrão e piroxicam (padrão interno foram 3,35 e 4,19 minutos, respectivamente. Este método apresentou linearidade na faixa de concentração entre 50-4000 ng/mL (R² = 0,9995, com limite de quantificação inferior de 50 ng/mL e exatidão de 114%. O método analítico desenvolvido neste trabalho demonstrou especificidade, linearidade, precisão e exatidão adequadas, permitindo sua aplicação em ensaios de bioequivalência.A simple, rapid and specific high-performance liquid cromatographic (HPLC method was developed and validated to estimate meloxicam (COX-2 inhibitor levels in human plasma. Piroxicam was used as internal standard. Reversed phase chromatography was conducted using a Synergi RP-MAX (150 x 4.6 mm column at 30 ºC and a mobile phase of acetonitrile and 0.025 mol/L pH 4,5 phosphate buffer (40:60, v/v, at a flow rate of 1mL/min. Analytes were detected at 364 nm. Plasma samples were acidified with 1 mol/L hydrochloric acid and extracted with tert-butyl methyl ether, evaporated to dryness, reconstituted in 250 mL of mobile phase and injected in the column. The retention time of

Counterion effects on nano-confined metal–drug–DNA complexes

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Nupur Biswas

2016-01-01

Full Text Available We have explored morphology of DNA molecules bound with Cu complexes of piroxicam (a non-steroidal anti-inflammatory drug molecules under one-dimensional confinement of thin films and have studied the effect of counterions present in a buffer. X-ray reflectivity at and away from the Cu K absorption edge and atomic force microscopy studies reveal that confinement segregates the drug molecules preferentially in a top layer of the DNA film, and counterions enhance this segregation.

Gelucire Based In Situ Gelling Emulsions: A Potential Carrier for Sustained Stomach Specific Delivery of Gastric Irritant Drugs

Directory of Open Access Journals (Sweden)

Ashwin Saxena

2013-01-01

Full Text Available Non steroidal anti-inflammatory drugs (NSAIDs are commonly prescribed medications to the geriatric patients for the treatment of arthritis and other painful disorders. The major side effects of NSAIDs are related to their effects on the stomach and bowels. The present study concerns assessment of the potential of liquid in situ gelling emulsion formulations (emulgels as patient compliant stomach specific sustained release carrier for the delivery of highly gastric irritant drug, Piroxicam. Emulgels were prepared, without using any emulgent, by mixing different concentrations of molten Gelucire 39/01 with low viscosity sodium alginate solution prepared in deionized water at 50°C. CaCO3 was used as buoyancy imparting as well as crosslinking agent. Emulgels so prepared were homogenous, physically stable, and rapidly formed into buoyant gelled mass when exposed to simulated gastric fluid (SGF, pH 1.2. Drug release studies carried out in SGF revealed significant retardation (P<0.05 of Piroxicam release from emulgels compared to conventional in situ gelling formulations prepared without Gelucire 39/01. Pharmacodynamic studies carried out in albino rats revealed significantly increased analgesic/anti-inflammatory response from in situ emulgels compared to conventional in situ gelling formulations. Further, in vivo toxicity studies carried out in albino rats revealed no signs of gastric ulceration upon prolonged dosing.

Health-related quality of life assessments in osteoarthritis during NSAID treatment.

Science.gov (United States)

de Bock, G H; Hermans, J; van Marwijk, H W; Kaptein, A A; Mulder, J D

1996-08-01

There is some evidence that nabumetone (1000 mg once daily) in comparison with piroxicam (20 mg once daily) in patients with OA in general practice is associated with a lower incidence and less severe occurrence of stomach pain but with more withdrawals due to lack of efficacy. The aim of this analysis was to investigate whether these differences are reflected in health-related quality of life assessments. Patients (n = 198) included in this study were selected in general practice according to a protocol. The patients were randomized and treated for a period of six weeks. Clinical assessments were performed by the general practitioner (CP) during treatment. The Sickness Impact Profile (SIP), the Activities of Daily Living (ADL), and a pain questionnaire were filled out by the patients before and after treatment. As measured with the SIP, the ADL and the pain questionnaire, there were no significant differences between nabumetone and piroxicam. The correlations between (changes in) patient assessments and (changes in) clinical assessments were low. The differences between the two drugs regarding withdrawals and adverse events were not reflected by patient health-related quality of life assessments. There was a low correlation between patient health-related quality of life assessment and clinical assessments. To get a complete picture of the efficacy and safety of a drug, patient health-related quality of life assessments should be a part of a clinical trial.

A short history of anti-rheumatic therapy. III. Non steroidal anti-inflammatory drugs

Directory of Open Access Journals (Sweden)

P. Marson

2011-06-01

Full Text Available The chemical advances of the 20th century led to the synthesis of non steroidal anti-inflammatory drugs (NSAIDs, beginning from phenylbutazone and indomethacin and continuing with other new drugs, including ibuprofen, diclofenac, naproxen, piroxicam and, more recently, the highly selective COX-2 inhibitors (coxibs. This progress derived from the discovery of the mechanism of action of these drugs: the inhibition of synthesis of prostaglandins due to the cycloxigenase enzyme system, according to the experimental contributions of John R. Vane.

Investigation of Pseudomonas aeruginosa quorum-sensing signaling system for identifying multiple inhibitors using molecular docking and structural analysis methodology.

Science.gov (United States)

Soheili, Vahid; Bazzaz, Bibi Sedigheh Fazly; Abdollahpour, Nooshin; Hadizadeh, Farzin

2015-12-01

Pseudomonas aeruginosa is an opportunistic human pathogen and a common Gram-negative bacterium in hospital-acquired infections. It causes death in many burn victims, cystic-fibrosis and neutropenic-cancer patients. It is known that P. aeruginosa biofilm maturation and production of cell-associated and extracellular virulence factors such as pyocyanin, elastase and rhamnolipids are under the control of a quorum-sensing (QS) system. Among several proteins involved in the Pseudomonas QS mechanism, LasR and PqsE play an important role in its cascade signaling system. They can cause increases in QS factors, biofilm maturation, and the production of virulence factors. Therefore, inhibition of these proteins can reduce the pathogenicity of P. aeruginosa. According to the structure of corresponding auto-inducers bound to these proteins, in silico calculations were performed with some non-steroidal anti-inflammatory drugs (NSAIDs) to estimate possible interactions and find the co-inhibitors of LasR and PqsE. The results showed that oxicams (Piroxicam and Meloxicam) can interact well with active sites of both proteins with the Ki of 119.43 nM and 4.0 μM for Meloxicam and 201.39 nM and 4.88 μM against LasR and PqsE, respectively. These findings suggested that Piroxicam and Meloxicam can be used as potential inhibitors for control of the P. aeruginosa QS signaling system and biofilm formation, and may be used in the design of multiple inhibitors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modulating drug release from gastric-floating microcapsules through spray-coating layers.

Directory of Open Access Journals (Sweden)

Wei Li Lee

Full Text Available Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone (PCL coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose. The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system.

Solid-phase extraction-spectrophotometric determination of uranium(VI) in natural waters

Energy Technology Data Exchange (ETDEWEB)

Sadeghi, Susan; Mohammadzadeh, Darush [Department of Chemistry, University of Birjand, Birjand (Iran); Yamini, Yadollah [Department of Chemistry, Tarbiat Moddars University, Tehran (Iran)

2003-03-01

A method for the extraction and determination of uranyl ion in natural waters using octadecyl bonded silica membrane disks modified with piroxicam and spectrophotometry with arsenazo(III) is proposed. The perconcentration step was studied with regard to experimental parameters such as amount of extractant, type and amount of eluent, pH, flow rates and tolerance limit of diverse ions on the recovery of uranyl ion. The limit of detection of the proposed method is 0.4 {mu}g L{sup -1} of uranyl. The method was applied to the recovery of uranyl from different water samples. (orig.)

Pharmacological treatment of actinic keratosis

Directory of Open Access Journals (Sweden)

Ewa Zwierzyńska

2016-09-01

Full Text Available Actinic keratosis (AK is a disease characterized by hyperkeratotic lesions on skin damaged by ultraviolet. radiation. These lesions may progress to squamous cell or basal cell carcinoma. Currently pharmacotherapy and different surgical procedures are used in AK therapy. The most common treatment options are 5-fluorouracil, imiquimod, diclofenac, ingenol mebutate, and first and third generation retinoids (retinol, adapalene, tazarotene. Furthermore, research is being carried out in order to test new medications including nicotinamide, resiquimod, piroxicam, potassium dobesilate and oleogel based on a triterpene extract (betulin, betulinic acid. Recently, the preventive effect of acetylsalicylic acid and celecoxib has also been investigated.

Solid-phase extraction-spectrophotometric determination of uranium(VI) in natural waters

International Nuclear Information System (INIS)

Sadeghi, Susan; Mohammadzadeh, Darush; Yamini, Yadollah

2003-01-01

A method for the extraction and determination of uranyl ion in natural waters using octadecyl bonded silica membrane disks modified with piroxicam and spectrophotometry with arsenazo(III) is proposed. The perconcentration step was studied with regard to experimental parameters such as amount of extractant, type and amount of eluent, pH, flow rates and tolerance limit of diverse ions on the recovery of uranyl ion. The limit of detection of the proposed method is 0.4 μg L -1 of uranyl. The method was applied to the recovery of uranyl from different water samples. (orig.)

Piroxicam treatment augments bone abnormalities in interleukin-10 knockout mice

DEFF Research Database (Denmark)

Holgersen, Kristine; Dobie, Ross; Farquharson, Colin

2015-01-01

BACKGROUND: Osteoporosis and fractures are common complications of inflammatory bowel disease. The pathogenesis is multifactorial and has been partly attributed to intestinal inflammation. The aim of this study was to evaluate bone status and assess the association between bone loss and gut infla...

Association of individual non-steroidal anti-inflammatory drugs and chronic kidney disease: a population-based case control study.

Directory of Open Access Journals (Sweden)

Ylenia Ingrasciotta

Full Text Available Non-steroidal anti-inflammatory agents (NSAIDs are known to be associated with renal damage. No clear evidence exists regarding differential risk of chronic kidney disease (CKD, specifically, across various NSAIDs.The aim of this population-based case-control study was to evaluate the association between use of individual NSAIDs and risk of CKD in a general population of Southern Italy.A nested case-control study was carried out using the general practice Arianna database, identifying incident CKD patients as cases and matched controls from 2006 to 2011. The date of first CKD diagnosis was defined as the index date (ID. Conditional logistic regressions were performed to estimate the risk of CKD associated with NSAIDs by class and individual drugs as compared to non-use during different time windows (within one year, six or three months prior to ID, with the latter being defined as current users. Among current users, the effect of cumulative exposure to these drugs was evaluated.Overall, 1,989 CKD cases and 7,906 matched controls were identified. A statistically significant increase in the risk of CKD was found for current users of oxicams (adjusted OR: 1.68; 95% CI: 1.15-2.44 and concerning individual compounds, for ketorolac (adj. OR: 2.54; 95% CI: 1.45-4.44, meloxicam (adj. OR: 1.98; 95% CI: 1.01-3.87 and piroxicam (adj. OR: 1.95; 95% CI: 1.19-3.21.The risk of CKD varies across individual NSAIDs. Increased risk has been found for ketorolac, which may precipitate subclinical CKD through acute renal damage, and long-term exposure to oxicams, especially meloxicam and piroxicam.

INVESTIGATION OF DRUG RELEASE FROM BIODEGRADABLE PLG MICROSPHERES: EXPERIMENT AND THEORY

Energy Technology Data Exchange (ETDEWEB)

ANDREWS, MALCOLM J. [Los Alamos National Laboratory; BERCHANE, NADER S. [Los Alamos National Laboratory; CARSON, KENNETH H. [Los Alamos National Laboratory; RICE-FICHT, ALLISON C. [Los Alamos National Laboratory

2007-01-30

Piroxicam containing PLG microspheres having different size distributions were fabricated, and in vitro release kinetics were determined for each preparation. Based on the experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the system size was increased. The mathematical model gave a good fit to the experimental release data.

New Synthesis, Structure and Analgesic Properties of Methyl 1-R-4-Methyl-2,2-Dioxo-1H-2λ6,1-Benzothiazine-3-Carboxylates

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Liliana Azotla-Cruz

2017-01-01

Full Text Available According to the principles of the methodology of bioisosteric replacements a series of methyl 1-R-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates has been obtained as potential analgesics. In addition, a fundamentally new strategy for the synthesis of compounds of this chemical class involving the introduction of N-alkyl substituent at the final stage in 2,1-benzothiazine nucleus already formed has been proposed. Using nuclear magnetic resonance (NMR spectroscopy, mass spectrometry and X-ray diffraction analysis it has been proven that in the DMSO/K2CO3 system the reaction of methyl 4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylate and alkyl halides leads to formation of N-substituted derivatives with good yields regardless of the structure of the alkylating agent. The peculiarities of NMR (1Н and 13С spectra of the compounds synthesized, their mass spectrometric behavior and the spatial structure are discussed. In N-benzyl derivative the ability to form a monosolvate with methanol has been found. According to the results of the pharmacological testing conducted on the model of the thermal tail-flick it has been determined that replacement of 4-ОН-group in methyl 1-R-4-hydroxy-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates for the methyl group is actually bioisosteric since all methyl 1-R-4-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxylates synthesized demonstrated a statistically significant analgesic effect. The majority of the substances can inhibit the thermal pain response much more effective than piroxicam in the same dose. Under the same conditions as an analgesic the N-methyl-substituted analog exceeds not only piroxicam, but more active meloxicam as well. Therefore, it deserves in-depth biological studies on other experimental models.

Postmarketing cohort study to assess the safety profile of oral dexketoprofen trometamol for mild to moderate acute pain treatment in primary care.

Science.gov (United States)

Carne, Xavier; Rios, Jose; Torres, Ferran

2009-10-01

Recently, new concerns on the safety profile of nonsteroidal anti-inflammatory drugs (NSAIDs) have been raised by the European Medicines Agency (EMEA) and other regulatory authorities. The safety profile of oral dexketoprofen trometamol for the treatment of acute mild to moderate pain of different causes in actual conditions of use in the primary care setting was assessed. A prospective cohort study was designed to evaluate the tolerability of dexketoprofen compared with other commonly prescribed analgesics. Medications were given according to specifications in the summary of product characteristics. The intensity of pain was assessed at baseline and at days 1 and 7 of drug treatment using a 100-mm visual analog scale (VAS). Adverse events (AEs) were recorded. A total of 7,337 patients (median age [IQR] = 46 [33-61] years) were included in the study comparing dexketoprofen (n = 5,429), diclofenac (n = 485), ibuprofen (n = 479), paracetamol (n = 459), metamizole (n = 207), aceclofenac (n = 103), naproxen (n = 74), piroxicam (n = 69) and dexibuprofen (n = 32). The reasons for use were: musculoskeletal disorders, headache, dysmenorrhea and odontalgia. Treatment compliance was very high. Metamizole-paracetamol and dexketoprofen showed the lowest prevalence of AEs (2.7% and 3.6%, respectively), while aceclofenac-diclofenac showed the highest prevalence (8.2%) (P dexketoprofen, 1.57 (0.79-3.13) for ibuprofen and dexibuprofen, 2.31 (0.64-8.27) for naproxen, 2.63 (0.85-8.15) for piroxicam and 3.37 (1.87-6.06) for aceclofenac-diclofenac. These results confirm the safety of oral treatment with dexketoprofen in patients with acute pain of various etiologies observed in previous studies and support the use of dexketoprofen as a first-line drug for the approved therapeutic indications. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

Modulation of expression of Programmed Death-1 by administration of probiotic Dahi in DMH-induced colorectal carcinogenesis in rats.

Science.gov (United States)

Mohania, Dheeraj; Kansal, Vinod K; Kumar, Manoj; Nagpal, Ravinder; Yamashiro, Yuichiro; Marotta, Francesco

2013-09-01

Interaction of probiotic bacteria with the host immune system elicits beneficial immune modulating effects. Although, there are many published studies on interaction of probiotics with immune system focusing on activation of immune system by bacterial cell wall through the engagement of Toll-like receptor family; very few studies have focused on molecules involved in the T-cell activation, and not much work has been executed to study the correlation of probiotics and programmed death-1 in colorectal carcinogenesis in animal models. Hence, the present study was carried out to assess the effect of probiotic Dahi on expression of programmed death (PD-1) in colorectum of 1, 2-dimethylhydrazine treated Wistar rats. DMH was injected subcutaneously at the rate of 40 mg/kg body weight per animal twice a week for 2 weeks. A total of 168 male Wistar rats were randomly allocated to seven groups, each group having twenty-four animals. The rats were euthanized at the 8th, 16th and 32nd week of the experiment and examined for the expression of PD-1 in colorectal tissues by immunohistochemical staining. Expression of PD-1 was observed in colorectal tissues of normal and DMH-treated rats. Feeding rats with probiotic Dahi or the treatment with piroxicam decreased the expression of PD-1 in DMH-induced colorectal mucosa, and the combined treatment with probiotic Dahi and piroxicam was significantly more effective in reducing the expression of PD-1. PD-1 expressed independent of carcinogen administration in normal colonic mucosa and may play a role in modulation of immune response in DMH-induced colorectal carcinogenesis. The present study suggests that probiotic Dahi can be used as an effective chemopreventive agent in the management of colorectal cancer.

In vitro and In vivo Characterisation of Piroxicam-Loaded Dika Wax ...

African Journals Online (AJOL)

HP

edu.ng; Tel.: +234- .... inversion and allowed to cool at room temperature to ... on a microscope slide, the slide was covered with a cover slip ... counted (n = 100) with the image analyzer, and ..... of lipospheres as carries for bioactive compounds.

Simultaneous determination of 12 pharmaceuticals in water samples by ultrasound-assisted dispersive liquid-liquid microextraction coupled with ultra-high performance liquid chromatography with tandem mass spectrometry.

Science.gov (United States)

Guan, Jin; Zhang, Chi; Wang, Yang; Guo, Yiguang; Huang, Peiting; Zhao, Longshan

2016-11-01

A new analytical method was developed for simultaneous determination of 12 pharmaceuticals using ultrasound-assisted dispersive liquid-liquid microextraction (DLLME) followed by ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS). Six nonsteroidal anti-inflammatory drugs (NSAIDs, ketoprofen, mefenamic acid, tolfenamic acid, naproxen, sulindac, and piroxicam) and six antibiotics (tinidazole, cefuroxime axetil, ciprofloxacin, sulfamethoxazole, sulfadiazine, and chloramphenicol) were extracted by ultrasound-assisted DLLME using dichloromethane (800 μL) and methanol/acetonitrile (1:1, v/v, 1200 μL) as the extraction and dispersive solvents, respectively. The factors affecting the extraction efficiency, such as the type and volume of extraction and dispersive solvent, vortex and ultrasonic time, sample pH, and ionic strength, were optimized. The ultrasound-assisted process was applied to accelerate the formation of the fine cloudy solution by using a small volume of dispersive solvent, which increased the extraction efficiency and reduced the equilibrium time. Under the optimal conditions, the calibration curves showed good linearity in the range of 0.04-20 ng mL -1 (ciprofloxacin and sulfadiazine), 0.2-100 ng mL -1 (ketoprofen, tinidazole, cefuroxime axetil, naproxen, sulfamethoxazole, and sulindac), and 1-200 ng mL -1 (mefenamic acid, tolfenamic acid, piroxicam, and chloramphenicol). The LODs and LOQs of the method were in the range of 0.006-0.091 and 0.018-0.281 ng mL -1 , respectively. The relative recoveries of the target analytes were in the range from 76.77 to 99.97 % with RSDs between 1.6 and 8.8 %. The developed method was successfully applied to the extraction and analysis of 12 pharmaceuticals in five kinds of water samples (drinking water, running water, river water, influent and effluent wastewater) with satisfactory results. Graphical Abstract Twelve pharmaceuticals in water samples analyted by UHPLC

Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage

Science.gov (United States)

Blandizzi, Corrado; Fornai, Matteo; Colucci, Rocchina; Natale, Gianfranco; Lubrano, Valter; Vassalle, Cristina; Antonioli, Luca; Lazzeri, Gloria; Tacca, Mario Del

2005-01-01

AIM: This study investigated the mechanisms of protection afforded by the proton pump inhibitor lansoprazole against gastric injury induced by different non-steroidal anti-inflammatory drugs (NSAIDs) in rats. METHODS: Male Sprague-Dawley rats were orally treated with indomethacin (100 µmol/kg), diclofenac (60 µmol/kg), piroxicam (150 µmol/kg) or ketoprofen (150 µmol/kg). Thirty minutes before NSAIDs, animals were orally treated with lansoprazole 18 or 90 µmol/kg. Four hours after the end of treatments, the following parameters were assessed: gastric mucosal PGE2, malondialdehyde (MDA), myeloperoxidase (MPO) or non-proteic sulfhydryl compounds (GSH) levels; reverse transcription-polymerase chain reaction (RT-PCR) of mucosal COX-2 mRNA; gastric acid secretion in pylorus-ligated animals; in vitro effects of lansoprazole (1-300 µmol/L) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate. RESULTS: All NSAIDs elicited mucosal necrotic lesions which were associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels were detected in the gastric mucosa of indomethacin- or piroxicam-treated animals. Indomethacin enhanced mucosal cyclooxygenase-2 expression, while not affecting cyclooxygenase-1. At the oral dose of 18 µmol/kg lansoprazole partly counteracted diclofenac-induced mucosal damage, whereas at 90 µmol/kg it markedly prevented injuries evoked by all test NSAIDs. Lansoprazole at 90 µmol/kg reversed also the effects of NSAIDs on MPO, MDA and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced cyclooxygenase-2 expression. However, both lansoprazole doses markedly inhibited acid secretion in pylorus-ligated rats. Lansoprazole concentration-dependently reduced the oxidation of LDLs in vitro. CONCLUSION: These results suggest that, besides the inhibition of acid secretion, lansoprazole protection against NSAID

Monitoring of multiple solid-state transformations at tablet surfaces using multi-series near-infrared hyperspectral imaging and multivariate curve resolution

DEFF Research Database (Denmark)

Alexandrino, Guilherme L; Khorasani, Milad Rouhi; Amigo Rubio, Jose Manuel

2015-01-01

The assessment of the solid-state stability of active pharmaceutical ingredient (API) and/or excipients in solid dosage forms during manufacturing and storage is mandatory for safeguarding quality of the final products. In this work, the solid-state transformations in tablets prepared as blends...... of piroxicam monohydrate (API), polyvinylpyrrolidone and the lactose forms monohydrate or anhydrate were studied when the tablets were exposed to the 23-120°C range. Multi-series near-infrared hyperspectral images were obtained from the surface of each sample for unveiling the local evolution of the solid......-state transformations. The preprocessed spectra from the images (dataset) were arranged in augmented matrices, according to the composition of the tablets, and the profile of the overlapped compounds (relative concentration) along the solid-state transformations in the pixels was resolved by using multivariate curve...

Topical Niosome Gel of Zingiber cassumunar Roxb. Extract for Anti-inflammatory Activity Enhanced Skin Permeation and Stability of Compound D.

Science.gov (United States)

Priprem, Aroonsri; Janpim, Khwanhatai; Nualkaew, Somsak; Mahakunakorn, Pramote

2016-06-01

An extract of Zingiber cassumunar Roxb. (ZC) was encapsulated in niosomes of which a topical gel was formed. (E)-4-(3',4'-dimethoxyphenyl)but-3-en-1-ol or compound D detected by a gradient HPLC was employed as the marker and its degradation determined to follow zero-order kinetics. Niosomes significantly retarded thermal-accelerated decomposition of compound D in the gel (p D. Niosomes enhanced in vitro permeation rate of compound D from the gel. Topical applications of ZC noisome gel gave a faster change in tail flick latency than piroxicam gel and hydrocortisone cream (p anti-inflammatory activity up to 6 h using croton oil-induced ear edema model in mice (p > 0.05). Thus, encapsulation of ZC extract in niosomes enhanced chemical stability and skin permeation with comparable topical anti-inflammatory effects to steroid and NSAID.

Radioiodination and bio-evaluation of some anti-inflammatory drugs

International Nuclear Information System (INIS)

Mohamed, H.H.

2009-01-01

This thesis deals with the electrophilic substitution radioiodination reaction of non-steroidal anti-inflammatory drugs namely, Piroxicam (Pirox), Meloxicam (Melox), Etodolac and Naproxen for using them as anti-inflammatory imaging agent. The factors affecting the percent of radiochemical yields such as drug concentration, ph of the reaction mixtures, different oxidizing agents, reaction time, temperature and different organic media were studied. We can divide the objective of this thesis into three parts: First part performs to compare the electrophilic substitution radioiodination reaction of Piroxicam (Pirox) and Meloxicam (Melox) with Iodine-125 where both chloramine-T (CAT) and iodogen were used as oxidizing agents. The maximum radiochemical yield of 125 I-Piroxicam ( 125 I-Pirox) was (94%) using 3.7 MBq of Na 125 I, 0.4 mM of Pirox as substrate, 3.6 mM of chloramine-T (CAT) as oxidizing agent in acetone at neutral ph=7 at 60 degree C within 20 min where the maximum radiochemical yield of ( 125 I-Melox) was (92%) using 0.7 mM of Melox as substrate, 0.62 mM of iodogen as oxidizing agent in acetone at neutral ph=7 at 25 degree C within 30 min. The radiochemical yields were determined by TLC using methylene chloride: ethyl acetate (3: 7 v/v) as a developing system and by high-pressure liquid chromatography (HPLC) using reversed phase RP-18 column and methanol: water (70: 30 v/v) as mobile phase at flow rate (1 ml/min). Tracers showed good localization in inflamed muscle either (septic or sterile). The collected data indicates that Pirox can be used as anti-inflammatory imaging agent at 24 h post injection however Melox can be used as anti-inflammatory imaging agent at 2 h due to its shorter biological half life (t 1/2 ) compared with Pirox. Second part describes a fast and efficient method for radiolabeling of etodolac with iodine-125, where both chloramine-T and iodogen were used as oxidizing agents. The labeling reaction was carried out via electrophilic

Triple-component nanocomposite films prepared using a casting method: Its potential in drug delivery

Directory of Open Access Journals (Sweden)

Sadia Gilani

2018-04-01

Full Text Available The purpose of this study was to fabricate a triple-component nanocomposite system consisting of chitosan, polyethylene glycol (PEG, and drug for assessing the application of chitosan–PEG nanocomposites in drug delivery and also to assess the effect of different molecular weights of PEG on nanocomposite characteristics. The casting/solvent evaporation method was used to prepare chitosan–PEG nanocomposite films incorporating piroxicam-β-cyclodextrin. In order to characterize the morphology and structure of nanocomposites, X-ray diffraction technique, scanning electron microscopy, thermogravimetric analysis, and Fourier transmission infrared spectroscopy were used. Drug content uniformity test, swelling studies, water content, erosion studies, dissolution studies, and anti-inflammatory activity were also performed. The permeation studies across rat skin were also performed on nanocomposite films using Franz diffusion cell. The release behavior of films was found to be sensitive to pH and ionic strength of release medium. The maximum swelling ratio and water content was found in HCl buffer pH 1.2 as compared to acetate buffer of pH 4.5 and phosphate buffer pH 7.4. The release rate constants obtained from kinetic modeling and flux values of ex vivo permeation studies showed that release of piroxicam-β-cyclodextrin increased with an increase in concentration of PEG. The formulation F10 containing 75% concentration of PEG showed the highest swelling ratio (3.42±0.02 in HCl buffer pH 1.2, water content (47.89±1.53% in HCl buffer pH 1.2, maximum cumulative drug permeation through rat skin (2405.15±10.97 μg/cm2 in phosphate buffer pH 7.4, and in vitro drug release (35.51±0.26% in sequential pH change mediums, and showed a significantly (p<0.0001 higher anti-inflammatory effect (0.4 cm. It can be concluded from the results that film composition had a particular impact on drug release properties. The different molecular weights of PEG have a

Phytochemical, analgesic and anti-inflammatory effects of the ethylacetate extract of the leaves of Pseudocedrella kotschyii.

Science.gov (United States)

Musa, Y M; Haruna, A K; Ilyas, M; Yaro, A H; Ahmadu, A A; Usman, H

2007-10-27

Phytochemical screening was carried out on the ethylacetate portion of the ethanolic extract of the leaves of Pseudocedrella kotschyii and then evaluated for its analgesic (acetic acid-induced writhing) and anti-inflammatory (raw egg albumin-induced oedema) activities in mice and rats respectively. Phytochemical screening of the ethylacetate partition portion of ethanolic extract revealed the presence of flavonoids, glycosides and tannins as major chemical constituents. Alkaloids saponins, cardiac glycosides, steroids were not dictated in the extract. The ethylacetate extract (50 and 100 mg/kg i.p) exhibited significant activity (pacetic acid-induced writhing in a dose dependent manner. In the anti-inflammatory activity the ethylacetate extract (50 and 100 mg/kg i.p.) caused a slight effect against the raw egg albumin-induced oedema. The effect was however observed not to be dose dependent. All these effects were compared with standard drug piroxicam (20 mg/kg i.p.).

High-resolution gene expression profiling using RNA sequencing in patients with inflammatory bowel disease and in mouse models of colitis

DEFF Research Database (Denmark)

Holgersen, Kristine; Kutlu, Burak; Fox, Brian

2015-01-01

pathways and assess the similarity between the experimental models and human disease. RNA sequencing was performed on colon biopsies from CD patients, UC patients and non-IBD controls. Genes shown to be significantly dysregulated in human IBD were used to study gene expression in colons from a piroxicam......Proper interpretation of data from preclinical animal studies requires a thorough knowledge about the pathophysiology of both the human disease and animal models. In this study, the expression of IBD-associated genes was characterised in mouse models of colitis to examine the underlying molecular......-accelerated colitis interleukin-10 knockout (PAC IL-10 k.o.), an adoptive transfer (AdTr) and a dextran sulfate sodium (DSS) colitis mouse model. 92 out of 115 literature-defined genes linked to IBD were significantly differentially expressed in inflamed mucosa of CD and/or UC patients compared with non-IBD controls...

Differential analgesic effects of low-dose epidural morphine and morphine-bupivacaine at rest and during mobilization after major abdominal surgery

DEFF Research Database (Denmark)

Dahl, J B; Rosenberg, J; Hansen, B L

1992-01-01

In a double-blind, randomized study, epidural infusions of low-dose morphine (0.2 mg/h) combined with low-dose bupivacaine (10 mg/h) were compared with epidural infusions of low-dose morphine (0.2 mg/h) alone for postoperative analgesia at rest and during mobilization and cough in 24 patients after...... elective major abdominal surgery. All patients in addition received systemic piroxicam (20 mg daily). No significant differences were observed between the groups at any assessment of pain at rest (P greater than 0.05), whereas pain in the morphine/bupivacaine group was significantly reduced during...... mobilization from the supine into the sitting position 12 and 30 h after surgical incision and during cough 8, 12, and 30 h after surgical incision (P less than 0.05). We conclude, that low-dose epidural bupivacaine potentiates postoperative low-dose epidural morphine analgesia during mobilization and cough...

Papillary Adenocarcinoma of the descending colon in a dog: case report

Directory of Open Access Journals (Sweden)

M.G.P.A. Ferreira

Full Text Available ABSTRACT The aim of this report was to describe the clinical findings and therapeutic management of a case of papillary adenocarcinoma of the descending colon in a Beagle. The patient presented soft stools, haematochezia, tenesmus, and dyschezia. Clinical examination revealed alterations on the ultrasonographic features of the descending colon suggestive of colitis and neoplasia. Following local mass resection, histopathology analysis revealed mild lymphoplasmocytic enteritis and papillary adenocarcinoma of the colon. Enterectomy for tumoral resection and biopsy of locoregional lymph nodes were carried out. Subsequent to the surgical procedure, it was possible to confirm the previous diagnosis and the tumor was classified as intestinal intraluminal papillary adenocarcinoma, with incomplete surgical margins. Adjuvant chemotherapy was performed using carboplatin, cyclophosphamide, and piroxicam, leading to remission of clinical signs and absence of any clinical or imaging alterations compatible with the patient’s previous clinical condition.

Cyclooxygenase inhibitors induce apoptosis in oral cavity cancer cells by increased expression of nonsteroidal anti-inflammatory drug-activated gene

International Nuclear Information System (INIS)

Kim, Kyung-Su; Yoon, Joo-Heon; Kim, Jin Kook; Baek, Seung Joon; Eling, Thomas E.; Lee, Won Jae; Ryu, Ji-Hwan; Lee, Jeung Gweon; Lee, Joo-Hwan; Yoo, Jong-Bum

2004-01-01

We have investigated whether NAG-1 is induced in oral cavity cancer cells by various NSAIDs and if apoptosis induced by NSAIDs can be linked directly with the induction of NAG-1. NAG-1 expression was increased by diclofenac, aceclofenac, indomethacin, ibuprofen, and sulindac sulfide, in the order of NAG-1 induction, but not by acetaminophen, piroxicam or NS-398. Diclofenac was the most effective NAG-1 inducer. Incubation with diclofenac inhibited cell proliferation and induced apoptosis. The expression of NAG-1 was observed in advance of the induction of apoptosis. Conditioned medium from NAG-1-overexpressing Drosophila cells inhibited SCC 1483 cells proliferation and induced apoptosis. In summary, some NSAIDs induce NAG-1 expression in oral cavity cancer cells and the induced NAG-1 protein appears to mediate apoptosis. Therefore, NSAIDs may be considered as a possible chemopreventive agent against oral cavity cancer

Analgesic and anti-inflammatory effects of the methanol stem bark extract of Prosopis africana.

Science.gov (United States)

Ayanwuyi, Lydia O; Yaro, Abdullahi H; Abodunde, Olajumoke M

2010-03-01

Prosopis africana (Guill. & Perr.) Taub. (Mimosoideae) is a shrub used for menstrual and general body pain in Nupe land in north central Nigeria. In this study, the methanol extract of the stem bark of Prosopis africana (at doses of 62.5, 125, and 250 mg/kg) was evaluated for analgesic and anti-inflammatory activities using acetic acid-induced writhing assay and carrageenan-induced inflammation in rats. The extract significantly (P acetic acid-induced writhing with the highest activity observed at the highest dose, 250 mg/kg (76.89%) comparable to that of piroxicam (83.16%) the standard agent used. In the carrageenan-induced inflammation assay, the extract showed significant anti-inflammatory activity (P screening revealed the presence of flavonoids, saponins, carbohydrates, cardiac glycosides, tannins, and alkaloids. The oral median lethal dose was found to be 3807.9 mg/kg in mice and > 5000 mg/kg in rats. This study supports the folkloric claim of the use of Prosopis africana in the management of pain.

Liquid chromatographic method for simultaneous determination of citalopram with NSAIDs in bulk drug, pharmaceutical formulation and human serum

International Nuclear Information System (INIS)

Ali, S.N.; Akram, S.

2017-01-01

A high performance liquid chromatographic method was developed and validated to simultaneously quantify citalopram with piroxicam, celecoxib and diclofenac sodium. Chromatographic analysis was performed at ambient temperature using Shimadzu Shim-pack CLC-ODS (M) 25M column linked to a UV-visible detector adjusted at 230 nm, employing 80:20 (v/v) methanol: water (pH 3.5) as mobile phase with flow rate 1.0 mL min-1. Validation was performed in the ranges 0.6-20, 0.9-28, 0.6-20 and 1.0-32 mu g mL-1 with lowest level corresponding to detection limit 16.45, 23.33, 27.66 and 14.44 ng mL-1 respectively. With-in the day precision ranged from 0.14-1.67% and between-day precision from 0.40-1.50%, accuracies were 99.61-100.86%. The analytes were successfully detected without any observable interference in pharmaceutical formulation and human serum samples demonstrating effectiveness of method. (author)

Use of diffusion-ordered NMR spectroscopy and HPLC-UV-SPE-NMR to identify undeclared synthetic drugs in medicines illegally sold as phytotherapies.

Science.gov (United States)

Silva, Lorena M A; Filho, Elenilson G A; Thomasi, Sérgio S; Silva, Bianca F; Ferreira, Antonio G; Venâncio, Tiago

2013-09-01

The informal (and/or illegal) e-commerce of pharmaceutical formulations causes problems that governmental health agencies find hard to control, one of which concerns formulas sold as natural products. The purpose of this work was to explore the advantages and limitations of DOSY and HPLC-UV-SPE-NMR. These techniques were used to identify the components of a formula illegally marketed in Brazil as an herbal medicine possessing anti-inflammatory and analgesic properties. DOSY was able to detect the major components present at higher concentrations. Complete characterization was achieved using HPLC-UV-SPE-NMR, and 1D and 2D NMR analyses enabled the identification of known synthetic drugs. These were ranitidine and a mixture of orphenadrine citrate, piroxicam, and dexamethasone, which are co-formulated in a remedy called Rheumazim that is used to relieve severe pain, but it is prohibited in Brazil because of a lack of sufficient pharmacokinetic and pharmacodynamic information. Copyright © 2013 John Wiley & Sons, Ltd.

The memory formalism in the diffusion of drugs through skin membrane

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Caputo, Michele; Cametti, Cesare, E-mail: cesare.cametti@roma1.infn.i [Dipartimento di Fisica, Universita di Roma ' La Sapienza' , Piazzale A. Moro 2, I-00185 Rome (Italy) and CNR-INFM-SOFT, Unita di Roma1 Rome (Italy)

2009-06-21

The diffusion of drugs across a composite structure such as a biological membrane is a rather complex phenomenon, where the assumptions on which the Fick equations are based are not always true, because of the inhomogeneous nature of the lipid membrane, the diffusion rate and the solubility of the drug being strongly dependent on the local position across the membrane. These problems are particularly strengthened in composite structures of a considerable thickness such as the human skin, where the high heterogeneity provokes the transport through different simultaneous pathways. In this note, we generalize the diffusion model based on Fick's second equation by the introduction of a space-dependent diffusion constant within the memory formalism (diffusion with memory) approach. The model predictions have been compared with experimental results concerning the permeation of two different compounds through human skin in vivo, such as piroxicam, an anti-inflammatory drug and 4-cyanophenol, a test chemical model compound. In both cases, reasonably good agreement has been found.

Transitional cell carcinomas in four fishing cats (Prionailurus viverrinus).

Science.gov (United States)

Sutherland-Smith, Meg; Harvey, Catherine; Campbell, Mark; McAloose, Denise; Rideout, Bruce; Morris, Patrick

2004-09-01

Transitional cell carcinomas (TCC) of the urinary bladder were diagnosed in four related fishing cats (Prionailurus viverrinus). The major clinical sign in each case was persistent hematuria unresponsive to medical therapy. Cystotomy and biopsy provided an antemortem diagnosis in three of the fishing cats before euthanasia because of progression of clinical signs. The diagnosis was made in the fourth cat after euthanasia because of renal failure. Hematuria improved temporarily in one of the cats diagnosed antemortem and treated with piroxicam and carboplatin. Attempts to isolate a herpesvirus in two of the cats failed. Histopathologic appearance of the TCC was similar to that described for other species. TCC metastasis to the lungs was noted at necropsy in one cat; metastatic disease was not noted in the other fishing cats on gross or histopathologic examination. TCC of the urinary bladder appears to be more prevalent in fishing cats than in other species of domestic or nondomestic felids.

The memory formalism in the diffusion of drugs through skin membrane

International Nuclear Information System (INIS)

Caputo, Michele; Cametti, Cesare

2009-01-01

The diffusion of drugs across a composite structure such as a biological membrane is a rather complex phenomenon, where the assumptions on which the Fick equations are based are not always true, because of the inhomogeneous nature of the lipid membrane, the diffusion rate and the solubility of the drug being strongly dependent on the local position across the membrane. These problems are particularly strengthened in composite structures of a considerable thickness such as the human skin, where the high heterogeneity provokes the transport through different simultaneous pathways. In this note, we generalize the diffusion model based on Fick's second equation by the introduction of a space-dependent diffusion constant within the memory formalism (diffusion with memory) approach. The model predictions have been compared with experimental results concerning the permeation of two different compounds through human skin in vivo, such as piroxicam, an anti-inflammatory drug and 4-cyanophenol, a test chemical model compound. In both cases, reasonably good agreement has been found.

On some toxinological aspects of the starfish Stellaster equestris (Retzius, 1805

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U Kanagarajan

2008-01-01

Full Text Available Whole-body extracts in methanol were obtained from the starfish Stellaster equestris. The crude toxin was fractionated stepwise using diethylaminoethyl (DEAE cellulose column chromatography. The crude toxin was lethal to male albino mice at a dose of 1.00 mL (containing 531.0 µg/mL protein when injected intraperitoneally (IP but the toxicity was abolished in all cases except one upon fractionation. The crude toxin and all the adsorbed fractions exhibited potent hemolytic activity on chicken, goat and human blood. However, group B human erythrocytes were resistant to lysis by all fractions and group O by most of the fractions. Paw edema in mice was caused by the crude toxin and all fractions. Pheniramine maleate and piroxicam blocked the toxicity when administered earlier than, or along with, the crude or fractionated toxins but not when administered after the envenomation. Pretreatment with either of these drugs also blocked edema formation.

Influence of some anti-inflammatory drugs on the activity of aryl hydrocarbon hydroxylase and the cytochrome P450 content

Energy Technology Data Exchange (ETDEWEB)

Mostafa, M.H.; Sheweita, S.A.; Abdel-Moneam, N.M. (Alexandria Univ. (Egypt))

1990-06-01

The metabolism of benzo({alpha})pyrene is mediated by the mixed function oxidase system including the cytochrome P450-dependent aryl hydrocarbon hydroxylase. The data of the present study revealed the ability of various commonly used anti-inflammatory drugs to alter the activity of this enzyme system, where all the tested drugs, namely phenyl butazone, ketoprofen, piroxicam, and acetaminophen, caused an increase in both the activity of aryl hydrocarbon hydroxylase and the cytochrome P450 content whether administered as a single dose or as a repeated dose for 6 consecutive days. The percentage of change for all drugs except phenyl butazone was proportional to the duration of drug administration. On the other hand, pyrazole which is chemically related to phenyl butazone, had no significant effect when administered as a single dose but caused a decrease in both studied parameters when administered as a repeated dose for 6 consecutive days. The mechanisms by which these commonly used drugs modify the aryl hydrocarbon hydroxylase activity and the cytochrome p450 content are discussed in the text.

Analgesic Usage in Elderly at Public Health Center: A study in West Java, Indonesias

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Gembong Soeyono Putro

2017-03-01

Full Text Available Background: Various analgesics prescriptions for elderly are not appropriate according to the guideline and can cause the increase of side effects such as gastric problems. Puskesmas as a public health center in Indonesia has an important role in anticipating this problem. The objectives of this study was to identify the analgesic usage in elderly patients at the public health center. Methods: This retrospective descriptive study was conducted for 3 months at Tanjungsari public health center, Sumedang, West Java, Indonesia, using total sampling. The data was taken from 417 medical records from 2013. The data taken from medical records were: sex, analgesic drug, diagnosis, and drug for gastric problem. Results: From the collected data, the most analgesics prescribed for the elderly patients was paracetamol, followed by Piroxicam, Mefenamic acid, and Ibuprofen. Not all of the elderly patients who received NSAIDs, were given gastric drug. Conclusions: The most prescribed analgesic drug given to elderly patients at the public health center is paracetamol. [AMJ.2017;4(1:16–9

Radiation proctitis in the rat. Sequential changes and effects of anti-inflammatory agents

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Northway, M.G.; Scobey, M.W.; Geisinger, K.R.

1988-11-01

Female Wistar rats were treated with single exposure irradiation to 2 cm of distal colon to cause radiation proctitis. All animals were evaluated by examination, colonoscopy and histologic evaluation for changes post-irradiation. Exposures of 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5 and 30 Gy caused dose-related clinical and histologic changes peaking at 7 to 15 days post-exposure. Rats treated with 20 Gy were colonoscoped and biopsied daily and showed sequential post-irradiation endoscopic changes ranging from mucosal edema and mild inflammatory changes to erosion and ulcers. Histologically, crypt abscess and mural wall necrosis similar to changes found in the human rectum after radiotherapy were noted. Treatment with nonsteroidal anti-inflammatory agents, (aspirin, indomethacin, piroxicam), misoprostol (a prostaglandin E1 analogue), or sucralfate (an anti-ulcer agent) did not ameliorate nor exacerbate radiation proctitis in rats exposed to 22.5 Gy. We conclude from these data that the female Wistar rat is a good model for studying radiation proctitis because endoscopic, histologic, and clinical changes seen post-exposure closely resemble those found in man.

Clinical, Epidemiological and Therapeutic Evaluation in 14 Cases of Inflammatory Breast Cancer in Canines

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Celina Gomes da Silva

2014-06-01

Full Text Available With the aim of evaluating clinical aspects, age, breed, presence of metastasis, chemotherapeutical protocol, use of COX-2 inhibitors and survival rate in female dogs diagnosed with inflammatory carcinoma at the Hospital Veterinario de Uberaba (HVU, a retrospective analysis was performed on the medical records of 14 female dogs seen at HVU between July, 2011 and July, 2012 and diagnosed with inflammatory breast cancer. The breeds included were crossbred, poodle, Brazilian terrier, teckel and Belgian shepherd. Average age: 11.1 years. Outbreaks of distant metastasis were detected in 7 animals, out of which 5 patients received COX-2 inhibitors as sole treatment and only 4 received chemotherapeutical treatment. The protocol, constituted by piroxicam, cyclophosphamide, carboplatin and doxorubicin showed the highest survival time (210 days. In conclusion, inflammatory carcinoma is a disease of bad prognosis, short survival time and produces systemic alterations that reduce therapeutic response. Apparently, the most accurate therapeutic form is the association of COX-2 inhibitors and chemotherapeutics; however, controlled clinical studies are needed in order to evaluate these suggestions.

Radioiodination and Biological Evaluation of some Drugs for Inflammatory Foci Imaging

International Nuclear Information System (INIS)

El Refaie, M.S.A.

2011-01-01

A radiopharmaceutical is defined as a chemical or pharmaceutical preparation labeled with a radionuclide in tracer or therapeutic concentration, used as a diagnostic or therapeutic agent. A radiopharmaceutical agent is usually administrated into a vein. Depending on which type of scan is being performed, the imaging will be done either immediately, a few hours later, or even several days after the injection. Imaging time varies, generally ranging from 20 to 45 minutes.In this thesis, we are more interested in the drugs that can be used for the treatment of all kinds of inflammation whether septic or aseptic. The inflammation by itself can be a controllable disease, but as the inflammation, specially the chronic type, can be the reason and the beginning of many more serious diseases as autoimmune disease, pulmonary disease, cardiovascular disease, neurological disease and cancer, the study and the early diagnosis of the inflammation can prevent many future problems for the patient. The study of the inflammation has been discussed before by labeling drugs with Iodine-125 for the imaging of inflammatory foci like etodolac, meloxicam, piroxicam and other drugs.

Radiation proctitis in the rat. Sequential changes and effects of anti-inflammatory agents

International Nuclear Information System (INIS)

Northway, M.G.; Scobey, M.W.; Geisinger, K.R.

1988-01-01

Female Wistar rats were treated with single exposure irradiation to 2 cm of distal colon to cause radiation proctitis. All animals were evaluated by examination, colonoscopy and histologic evaluation for changes post-irradiation. Exposures of 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5 and 30 Gy caused dose-related clinical and histologic changes peaking at 7 to 15 days post-exposure. Rats treated with 20 Gy were colonoscoped and biopsied daily and showed sequential post-irradiation endoscopic changes ranging from mucosal edema and mild inflammatory changes to erosion and ulcers. Histologically, crypt abscess and mural wall necrosis similar to changes found in the human rectum after radiotherapy were noted. Treatment with nonsteroidal anti-inflammatory agents, (aspirin, indomethacin, piroxicam), misoprostol (a prostaglandin E1 analogue), or sucralfate (an anti-ulcer agent) did not ameliorate nor exacerbate radiation proctitis in rats exposed to 22.5 Gy. We conclude from these data that the female Wistar rat is a good model for studying radiation proctitis because endoscopic, histologic, and clinical changes seen post-exposure closely resemble those found in man

Alkylglycerol Derivatives, a New Class of Skin Penetration Modulators

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Sergio Alberto Bernal-Chávez

2017-01-01

Full Text Available The absorption modulating activity of two alkylglycerol derivatives (batyl and chimyl alcohol on skin barrier properties was evaluated. Biophysical tests such as transepidermal water loss (TEWL and attenuated total reflectance–Fourier transform infrared (ATR-FTIR spectroscopy, as well as in vitro skin permeation studies, were performed in order to determine the effect of these compounds as chemical absorption modulators. Four drugs were used as models: three NSAIDS (diclofenac, naproxen, and piroxicam and glycyrrhizic acid. The results showed that treatment of the skin with alkylglycerols caused (i a reduction on the amount of drug permeated; (ii a reduction in TEWL; and (iii changes in the ATR-FTIR peaks of stratum corneum lipids, indicative of a more ordered structure. All of these findings confirm that alkyl glycerols have an absorption retarding effect on the drugs tested. Such effects are expected to give rise to important applications in the pharmaceutical and cosmetic sectors, in cases where it is desirable for the drug to remain in the superficial layers of the skin to achieve a local effect.

Autonomic failure mimicing dopamine agonist induced vertigo in a patient with macroprolactinoma.

Science.gov (United States)

Seiler, L; Braune, S; Borm, K; Magerkurth, C; Talazko, J; Peters, T; Reincke, M

2002-10-01

A 68-year-old man presented with general fatigue, increasing adynamia, weakness, vertigo and recurrent syncope. Six weeks earlier the diagnosis of a macroprolactinoma had been established based on a greatly elevated prolactin concentration (161 170 micro U/l) and MR-evidence of a 3.5 cm measuring pituitary mass. The patient had been started on cabergoline (1.5 mg weekly). Orthostatic hypotension due to the dopamine agonist was considered very likely and carbergoline therapy was stopped. However, there was no relief of the symptoms and further syncopes followed. Testing of blood pressure and heart rate regulation, selective testing of postganglionic cardiac neurons with [ 123 J] metaiodobenzylguanidine scintigraphy provided evidence of grossly impaired neurogenic cardiovascular regulation due to failure of postganglionic efferent sympathetic activity. This is characteristic for pure autonomic failure. The patient was treated symptomatically with high fluid intake, compression stockings, fludrohydrocortisone (0.1 mg o.d.s.), piroxicam (20 mg o.d.s.) and etilephrin (10 mg q.d.s.), which enabled him to cope with daily activities without syncope. This case shows that vertigo in a patient with macroprolactinoma is not always related to drug therapy but may be related to other causes.

Time-Gated Raman Spectroscopy for Quantitative Determination of Solid-State Forms of Fluorescent Pharmaceuticals.

Science.gov (United States)

Lipiäinen, Tiina; Pessi, Jenni; Movahedi, Parisa; Koivistoinen, Juha; Kurki, Lauri; Tenhunen, Mari; Yliruusi, Jouko; Juppo, Anne M; Heikkonen, Jukka; Pahikkala, Tapio; Strachan, Clare J

2018-04-03

Raman spectroscopy is widely used for quantitative pharmaceutical analysis, but a common obstacle to its use is sample fluorescence masking the Raman signal. Time-gating provides an instrument-based method for rejecting fluorescence through temporal resolution of the spectral signal and allows Raman spectra of fluorescent materials to be obtained. An additional practical advantage is that analysis is possible in ambient lighting. This study assesses the efficacy of time-gated Raman spectroscopy for the quantitative measurement of fluorescent pharmaceuticals. Time-gated Raman spectroscopy with a 128 × (2) × 4 CMOS SPAD detector was applied for quantitative analysis of ternary mixtures of solid-state forms of the model drug, piroxicam (PRX). Partial least-squares (PLS) regression allowed quantification, with Raman-active time domain selection (based on visual inspection) improving performance. Model performance was further improved by using kernel-based regularized least-squares (RLS) regression with greedy feature selection in which the data use in both the Raman shift and time dimensions was statistically optimized. Overall, time-gated Raman spectroscopy, especially with optimized data analysis in both the spectral and time dimensions, shows potential for sensitive and relatively routine quantitative analysis of photoluminescent pharmaceuticals during drug development and manufacturing.

Effects of benzydamine eye drops on the rabbit's eye reaction to surgical, physical, and chemical stimuli

Energy Technology Data Exchange (ETDEWEB)

Tomazzoli, L.; Bonora, A.; Luparini, M.R.; Durando, L.; Ciarniello, M.G.; Cioli, V.; Bonomi, L.

The effects of benzydamine eye drops on the ocular reaction to different irritating stimuli in rabbits are reported. Benzydamine at the concentration of 0.1% reduces inflammatory tissue changes induced by AgNO3 burning of the cornea and inhibits the blood-aqueous barrier breakdown due to peripheral iridectomy or laser irradiation of the iris. Benzydamine reduces the aqueous PGE2 concentration to a similar extent as a 0.5% commercially available eye drop formulation of piroxicam. This result is in contrast with previous in vitro results demonstrating that benzydamine is devoid of any effects on PG synthesis. The possibility that PGE2 reduction is an indirect effect due to other biochemical activities of benzydamine is discussed. In the normal eye benzydamine manifests a local anaesthetic effect which is not accompanied by irritative changes in the anterior segment of the eye, changes in the intraocular pressure or pupillary size. It is suggested that in the clinical use of benzydamine eye drops the local anaesthetic activity may contribute to reducing both the neurogenic component of ocular inflammation and acute pain following injuries to the eye.

Synthesis, Spatial Structure and Analgesic Activity of Sodium 3-Benzylaminocarbonyl-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazin-4-olate Solvates

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Igor V. Ukrainets

2016-10-01

Full Text Available In order to obtain and then test pharmocologically any possible conformers of the new feasible analgesic N-benzyl-4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide, its 4-O-sodium salt was synthesized using two methods. X-ray diffraction study made possible to determine that, depending on the chosen synthesis conditions, the above-mentioned compound forms either monosolvate with methanol or monohydrate, where organic anion exists in the form of three different conformers. Pharmacological testing of the two known pseudo-enantiomeric forms of the original N-benzylamide and of the two solvates of its sodium salt was performed simultaneously under the same conditions and in equimolar doses. Comparison of the results obtained while studying the peculiarities of the synthesized compounds spatial structure and biological properties revealed an important structure-action relationship. In particular, it was shown that the intensity of analgesic effect of different conformational isomers of N-benzyl-4-hydroxy-1-methyl-2,2-dioxo-1H-2λ6,1-benzothiazine-3-carboxamide may change considerably: while low active conformers are comparable with piroxicam, highly active conformers are more than twice as effective as meloxicam.

Green analytical determination of emerging pollutants in environmental waters using excitation-emission photoinduced fluorescence data and multivariate calibration.

Science.gov (United States)

Hurtado-Sánchez, María Del Carmen; Lozano, Valeria A; Rodríguez-Cáceres, María Isabel; Durán-Merás, Isabel; Escandar, Graciela M

2015-03-01

An eco-friendly strategy for the simultaneous quantification of three emerging pharmaceutical contaminants is presented. The proposed analytical method, which involves photochemically induced fluorescence matrix data combined with second-order chemometric analysis, was used for the determination of carbamazepine, ofloxacin and piroxicam in water samples of different complexity without the need of chromatographic separation. Excitation-emission photoinduced fluorescence matrices were obtained after UV irradiation, and processed with second-order algorithms. Only one of the tested algorithms was able to overcome the strong spectral overlapping among the studied pollutants and allowed their successful quantitation in very interferent media. The method sensitivity in superficial and underground water samples was enhanced by a simple solid-phase extraction with C18 membranes, which was successful for the extraction/preconcentration of the pollutants at trace levels. Detection limits in preconcentrated (1:125) real water samples ranged from 0.04 to 0.3 ng mL(-1). Relative prediction errors around 10% were achieved. The proposed strategy is significantly simpler and greener than liquid chromatography-mass spectrometry methods, without compromising the analytical quality of the results. Copyright © 2014 Elsevier B.V. All rights reserved.

[Use of topical non-steroidal anti-inflammatory drugs in aggravated and decompensated arthroses].

Science.gov (United States)

Chlud, K

1999-01-01

Pain in osteoarthritis of the big weight bearing joints is either derived from periarticular ligaments, tendons, fascias, muscles, bursae--periarthropathy as sign of decompensation or from the reactive synovitis with or without effusion. NSAIDs (ibuprofen, diclofenac, indometacin, some salicylates, etofenamate and piroxicam) have demonstrated relevant advantages of the percutaneous route over the systemic one in soft tissue rheumatism. NSAIDs, mentioned above, locally administered as cream, gel or spray, quickly penetrate through the corneal layer of the skin and the site of application, reach highly effective concentrations in subcutis, fascias, tendons, ligaments and muscles, less in joint-capsule and -fluid indicating direct penetration. The blood levels of topical NSAIDs are extremely low with no systemic side effects, especially no gastric toxicity; however, local skin irritation is observed (1 to 2%). In contrast to this, systemic (oral) NSAIDs lead primarily via high blood levels to a lower concentration--only one tenth--in periarticular soft tissues with a high incidence of side effects. In conclusion the percutaneous application of certain NSAIDs has become a well established therapeutic regimen in painful osteoarthritis and in all other inflammatory degenerative and posttraumatic alterations of soft tissue structure.

Enhancement by platelets of oxygen radical responses of human neutrophils

International Nuclear Information System (INIS)

McCulloch, K.K.; Powell, J.; Johnson, K.J.; Ward, P.A.

1986-01-01

When human blood neutrophils were incubated with immune complexes (consisting of IgG antibody) in the presence of platelets, there was a 2 to 10 fold enhancement in the generation of O- 2 and H 2 O 2 . This enhancement phenomenon was proportional to the dose of immune complex added and the number of platelets present. The response was not agonist specific since similar enhancement also occurred with the following agonists: phorbol myristate acetate, opsonized zymosan particles and the chemotactic peptide N-formyl-met-leu-phe. The platelet related phenomenon of enhanced O- 2 generation could not be reproduced by the addition of serotonin, histamine or platelet-derived growth factor and was not affected by prior treatment of platelets with cyclooxygenase inhibitors (indomethacin, piroxicam) or lipoxygenase inhibitors (nafazatrom, BW755C or nordihydroguaiaretic acid). However, activation of platelets by thrombin caused release into the platelet supernatant fluid of a factor that, only in the presence of immune complexes, caused enhanced O- 2 responses to neutrophils. These data indicate that platelets potentiate oxygen radical responses of human neutrophils and suggest a mechanisms by which platelets may participate in tissue injury which is mediated by oxygen radical products from activated neutrophils

Establishment of cocrystal cocktail grinding method for rational screening of pharmaceutical cocrystals.

Science.gov (United States)

Yamamoto, Katsuhiko; Tsutsumi, Shunichirou; Ikeda, Yukihiro

2012-11-01

Cocrystals (CCs) used in the pharmaceutical industry are defined as complex crystals formed by reaction between an API and a cocrystal former (CCF); unlike salts, CCs do not show proton transfer. Recently, pharmaceutical CCs have been used to improve the drug-likeness of APIs, such as solubility and stability. Grinding is more effective for CC synthesis than crystallization from solution because in the former case, the API can predominantly interact with the CCF without being affected by solvents. However, this method is tedious because the API is ground with only one CCF at a time. We developed a cocktail cocrystal grinding (CCG) method, in which a mixture of CCFs having the same functional group was used. No false negatives/positives were observed in CCG when carbamazepine was used as the model compound. This method could be used to obtain CCs of piroxicam and spironolactone. False negatives were observed for only one compound from among three model compounds, indicating that CCG facilitates efficient CC detection and that it has higher throughput than does the conventional method. Further, CCG is fast and suitable for rational CC screening, and it helps identify the partial structure of CCFs that forms synthons with an API. Copyright © 2012 Elsevier B.V. All rights reserved.

Enhancement by platelets of oxygen radical responses of human neutrophils

Energy Technology Data Exchange (ETDEWEB)

McCulloch, K.K.; Powell, J.; Johnson, K.J.; Ward, P.A.

1986-03-01

When human blood neutrophils were incubated with immune complexes (consisting of IgG antibody) in the presence of platelets, there was a 2 to 10 fold enhancement in the generation of O-/sub 2/ and H/sub 2/O/sub 2/. This enhancement phenomenon was proportional to the dose of immune complex added and the number of platelets present. The response was not agonist specific since similar enhancement also occurred with the following agonists: phorbol myristate acetate, opsonized zymosan particles and the chemotactic peptide N-formyl-met-leu-phe. The platelet related phenomenon of enhanced O-/sub 2/ generation could not be reproduced by the addition of serotonin, histamine or platelet-derived growth factor and was not affected by prior treatment of platelets with cyclooxygenase inhibitors (indomethacin, piroxicam) or lipoxygenase inhibitors (nafazatrom, BW755C or nordihydroguaiaretic acid). However, activation of platelets by thrombin caused release into the platelet supernatant fluid of a factor that, only in the presence of immune complexes, caused enhanced O-/sub 2/ responses to neutrophils. These data indicate that platelets potentiate oxygen radical responses of human neutrophils and suggest a mechanisms by which platelets may participate in tissue injury which is mediated by oxygen radical products from activated neutrophils.

SUITABILITY OF MEDICATIONS USED BY THE ELDERLY PARTICIPANTS OF A SOCIAL GROUP, ACCORDING TO THE BEERS CRITERIA

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Geysa Donária de Miranda Mascarenhas

2014-09-01

Full Text Available The dynamic process defined as aging progressively reduces the functional capacity of the elderly and added to the lifestyle, they can to testify to the high number of pathologies. Thus, pharmacotherapy for this age group requires special care, keeping in view its peculiarities. Given this need, a group of researchers has developed criteria that allowed the identification of inappropriate medications. Thus, the aim of this study was to investigate the suitability of medications used by the elderly participants of a social group, in Vitória da Conquista, BA, according to the Beers criteria. This research was an exploratory descriptive study and data collection conducted through semi - structured interviews. It was asked to bring all the elderly who were using medications and / or prescriptions. It was found that 12.7% of the drugs used by the elderly appeared in the list of inappropriate medicines and 42% of respondents make use of polypharmacy. Among the most prescribed inappropriate medications, there is acetylsalicylic acid, diclofenac, diazepam, piroxicam, ibuprofen and amitriptyline. The class of inappropriate drugs most used by seniors was anti - inflammatory drugs. Given this, all health professionals need to put into practice the criteria for selecting medications this age group as the reality of existing drugs in Brazil.

Stevens–Johnson syndrome and toxic epidermal necrolysis in an academic hospital setting: a 5-year retrospective study

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Ewa Stocka-Łabno

2016-10-01

Full Text Available Introduction: Toxic epidermal necrolysis and Stevens–Johnson syndrome are acute life-threatening mucocutaneous reactions to drugs. The aims of the study were to identify these drugs and characterize population prone to these reactions. Materials and Methods: Data including demographics, culprit drug, clinical characteristics, course of disease, treatment given, and therapeutic responses were retrospectively collected from medical records of 31 patients admitted to Department of Dermatology from January 2009 to December 2014. Results: Drugs most commonly involved in Stevens–Johnson syndrome were antimicrobials: ciprofloxacin, doxycycline, cefuroxime, trimethoprim, amoxicillin, clindamycin, co-trimoxazole (50% of patients and nonsteroidal anti-inflammatory drugs: ibuprofen, naproxen, metamizole, piroxicam (29% of patients. Drugs involved in toxic epidermal necrolysis were antimicrobials: sulfasalazine, co-trimoxazole, cefuroxime, clindamycin (71% of patients and anticonvulsants: lamotrigine (29% of patients. The comorbidities’ characteristic for the group of patients affected by toxic epidermal necrolysis were psychiatric and autoimmune disorders. The most common complication was infection. Two patients died and in both cases the cause of death was sepsis. Conclusion: The study indicates that in observed population drugs with the highest risk of most severe reactions are lamotrigine (anticonvulsant and antimicrobials (most commonly sulfonamides, therefore it is advisable to consider carefully administration of these drugs, especially to patients with history of autoimmune reactions.

Suitability of medications used by the elderly participants of a social group, according to the Beers criteria

Directory of Open Access Journals (Sweden)

Geysa Donária de Miranda Mascarenhas

2014-07-01

Full Text Available The dynamic process defined as aging progressively reduces the functional capacity of the elderly and added to the lifestyle, they can to testify to the high number of pathologies. Thus, pharmacotherapy for this age group requires special care, keeping in view its peculiarities. Given this need, a group of researchers has developed criteria that allowed the identification of inappropriate medications. Thus, the aim of this study was to investigate the suitability of medications used by the elderly participants of a social group, in Vitória da Conquista, BA, according to the Beers criteria. This research was an exploratory descriptive study and data collection conducted through semi - structured interviews. It was asked to bring all the elderly who were using medications and / or prescriptions. It was found that 12.7% of the drugs used by the elderly appeared in the list of inappropriate medicines and 42% of respondents make use of polypharmacy. Among the most prescribed inappropriate medications, there is acetylsalicylic acid, diclofenac, diazepam, piroxicam, ibuprofen and amitriptyline. The class of inappropriate drugs most used by seniors was anti - inflammatory drugs. Given this, all health professionals need to put into practice the criteria for selecting medications this age group as the reality of existing drugs in Brazil.

POLYURETHANE COMPOSITES AS DRUG CARRIERS:: RELEASE PATTERNS

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M. V. Grigoreva

2013-10-01

Full Text Available Biodegradable polyurethanes attract interest of those developing composite materials for biomedical applications. One of their features is their ability to serve as carriers, or matrixes, for medicines and other bioactive compounds to produce a therapeutic effect in body through targeted and/or prolonged delivery of these compounds in the process of their controlled release from matrix. The review presents polyurethane composites as matrices for a number of drugs. The relation between structure of the composites and their degradability both in vitro and in vivo and the dependence of drug release kinetics on physicochemical properties of polyurethane matrix are highlighted. The release of drugs (cefazolin, naltrexone and piroxicam from the composites based on cross-linked polyurethanes (synthesized from laprols, Mw between 1,500 and 2,000 Da and toluylene diisocyanate demonstrated more or less the same pattern (about 10 days in vitro and three to five days in vivo. In contrast, the composites with dioxydine based on a linear polyurethanes (synthesized from oligotetramethilene glycol, Mw 1,000 Da, diphenylmethane-4,4’-diisocyanate and 1,4-butanediol retained their antimicrobial activity at least 30 days. They also showed a significantly higher breaking strength as compared to that of the composites based on cross-linked polyurethanes.

Changes in colonic motility induced by sennosides in dogs: evidence of a prostaglandin mediation.

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Staumont, G; Fioramonti, J; Frexinos, J; Bueno, L

1988-01-01

The effects of sennosides on colonic motility were investigated in eight conscious dogs chronically fitted with two strain gauge transducers in the proximal colon, an intracolonic silicone catheter and a polyethylene catheter implanted in a branch of the right colonic artery. Oral sennosides (30 mg/kg) inhibited colonic motility for 12 to 18 h after a three to six hours delay, and associated with giant contractions and diarrhoea. The minimal oral dose of sennosides to produce such changes varied from 5 to 15 mg/kg. Intracolonic sennosides at the minimal effective dose and at 30 mg/kg reproduced the effects of oral sennosides, but with a shorter latency (0.5-1.5 h). Intracolonic PGE2 (100 micrograms/kg) in viscous gel medium or intra-arterial PGE2 (10 micrograms/h) inhibited colonic motility and induced giant contractions often associated with defecation. The colonic motor changes induced by intracolonic sennosides at the minimal effective dose, but not those induced by intracolonic PGE2, were blocked by intra-arterial indomethacin (10 micrograms/h) or piroxicam (5 micrograms/h). These results suggest that colonic motor actions of sennosides are mediated through a local prostaglandins synthesis, as they were blocked by cyclooxygenase inhibitor and reproduced by PGE2. PMID:3197991

Comparison of Mass Transfer Models for Determination of the Intestinal Permeability

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P Zakeri-Milani

2008-09-01

Full Text Available Background and the purpose of the study: In determination of the permeability of the intestinal wall by external perfusion techniques, several models have been proposed. In the present study three models were used for experimental results that differ in their convection and diffusion assumptions. Material and Methods: Permeability coefficients for 13 compounds (metoprolol, propranolol, naproxen, ketoprofen, furosemide, hydrochlorothiazide, cimetidine, ranitidine, atenolol, piroxicam, antipyrine, ibuprofen and carbamazepine with known human intestinal permeability values were determined in anaesthetized rats by different mass transfer models and plotted versus the observed human intestinal permeabilities. Results: The calculated dimensionless wall permeability values were in the range of 0.37 - 4.85, 0.38-6.54 and 0.41-16.59 for complete radial mixing, mixing tank and laminar flow models respectively. The results indicated that all of the models work relatively well for our data despite fundamentally different assumptions. The wall permeabilities were in the order laminar flow > mixing tank > complete radial mixing. Conclusion: Although laminar flow model provides the most direct measure of the intrinsic wall permeability, it has limitations for highly permeable drugs such as ibuprofen. The normal physiological hydrodynamics is more complex and more investigation is required to find out the real hydrodynamics.

Transport rankings of non-steroidal antiinflammatory drugs across blood-brain barrier in vitro models.

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Iveta Novakova

Full Text Available The aim of this work was to conduct a comprehensive study about the transport properties of NSAIDs across the blood-brain barrier (BBB in vitro. Transport studies with celecoxib, diclofenac, ibuprofen, meloxicam, piroxicam and tenoxicam were accomplished across Transwell models based on cell line PBMEC/C1-2, ECV304 or primary rat brain endothelial cells. Single as well as group substance studies were carried out. In group studies substance group compositions, transport medium and serum content were varied, transport inhibitors verapamil and probenecid were added. Resulted permeability coefficients were compared and normalized to internal standards diazepam and carboxyfluorescein. Transport rankings of NSAIDs across each model were obtained. Single substance studies showed similar rankings as corresponding group studies across PBMEC/C1-2 or ECV304 cell layers. Serum content, glioma conditioned medium and inhibitors probenecid and verapamil influenced resulted permeability significantly. Basic differences of transport properties of the investigated NSAIDs were similar comparing all three in vitro BBB models. Different substance combinations in the group studies and addition of probenecid and verapamil suggested that transporter proteins are involved in the transport of every tested NSAID. Results especially underlined the importance of same experimental conditions (transport medium, serum content, species origin, cell line for proper data comparison.

Amtolmetin: A Reappraisal of NSAID with Gastroprotection.

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Garg, Amit; Shoeb, Ahsan; Moodahadu, Latha Subramanya; Sharma, Akhilesh; Gandhi, Arul; Akku, Shyam

2016-01-01

Aim. To assess the gastrosparing effect of amtolmetin guacyl (AMG) against other nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with osteo-/rheumatoid arthritis. Methods. A literature search was done in the electronic databases (PubMed, Google Scholar, Embase, and Scopus) with key words "amtolmetin guacyl", "amtolmetin", and "arthritis"; filters were applied to obtain publications between 01-Jan-1985 and 01-Oct-2015, which were "clinical trials" in osteo-/rheumatoid arthritis patients and in "English language." Studies were assessed using the Jadad criteria and trials with score ≥ 3 were included in the analysis to compare the safety and efficacy of AMG against other NSAIDs. Results. Search yielded 19 publications of which 3 were included for analysis. Baseline characteristics of patients were comparable between the AMG group and other NSAIDs (diclofenac, celecoxib, and piroxicam) groups in all trials. Efficacy of AMG was similar to the other NSAIDs compared in the trials. The number of adverse events (AEs) reported was similar between both the groups; however, severe AEs reported were significantly lower in the AMG group. Of note was the significant lower number of duodenal ulcers after treatment in the AMG group. Conclusions. AMG has efficacy similar to other NSAIDs and a safer gastrointestinal AE profile when compared to the other NSAIDs.

Optimal management of orthodontic pain.

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Topolski, Francielle; Moro, Alexandre; Correr, Gisele Maria; Schimim, Sasha Cristina

2018-01-01

Pain is an undesirable side effect of orthodontic tooth movement, which causes many patients to give up orthodontic treatment or avoid it altogether. The aim of this study was to investigate, through an analysis of the scientific literature, the best method for managing orthodontic pain. The methodological aspects involved careful definition of keywords and diligent search in databases of scientific articles published in the English language, without any restriction of publication date. We recovered 1281 articles. After the filtering and classification of these articles, 56 randomized clinical trials were selected. Of these, 19 evaluated the effects of different types of drugs for the control of orthodontic pain, 16 evaluated the effects of low-level laser therapy on orthodontic pain, and 21 evaluated other methods of pain control. Drugs reported as effective in orthodontic pain control included ibuprofen, paracetamol, naproxen sodium, aspirin, etoricoxib, meloxicam, piroxicam, and tenoxicam. Most studies report favorable outcomes in terms of alleviation of orthodontic pain with the use of low-level laser therapy. Nevertheless, we noticed that there is no consensus, both for the drug and for laser therapy, on the doses and clinical protocols most appropriate for orthodontic pain management. Alternative methods for orthodontic pain control can also broaden the clinician's range of options in the search for better patient care.

Perbedaan Tolerabilitas Meloxicam dengan Natrium Diklofenak terhadap Saluran Cerna pada Pasien Rawat Jalan di PoliklinikPenyakit Saraf Rumah Sakit Angkatan Laut Dr. Mintohardjo Jakarta 2011

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Lailan Azizah

2013-06-01

Full Text Available Abstrak Obat anti inflamasi non steroid dihubungkan dengan insiden efek samping yang tinggi terhadap saluran cerna. Penghambatan enzim siklooksigenase merupakan dasar efikasi dan toksisitas obat anti inflamasi non steroid. Penelitian ini bertujuan untuk mengevaluasi jenis obat anti inflamasi non steroid yang digunakan di poliklinik penyakit saraf Rumah Sakit Angkatan Laut (Rumkital Dr. Mintohardjo Jakarta dan mengevaluasi tolerabilitas meloxicam 15 mg dengan natrium diklofenak 100 mg terhadap saluran cerna. Metode penelitian ini observasi cross-sectional dan cohortprospektif pada periode Desember 2010–Maret 2011. Pengambilan data mengenai keluhan dispepsia terkait penggunaan obat anti inflamasi non steroid terdiri dari nyeri abdomen atas, mual, muntah, kembung abdomen, dan cepat kenyang dilakukan melalui wawancara berdasarkan kuesioner the porto alegre dyspeptic symptoms questionnaire (PADYQyaitu sebelum, setelah 2 minggu, dan setelah 4 minggu pengobatan. Hasil penelitian menyatakan obat anti inflamasi non steroid paling banyak diresepkan di poliklinik penyakit saraf Rumkital Dr. Mintohardjo adalah meloxicam (48,21%, selanjutnya natrium diklofenak (31,07%, asam mefenamat (15,36%, piroxicam (3,93% dan asetaminofen (1,43%. Meloxicam secara bermakna menunjukkan risiko yang lebih kecil terhadap insiden saluran cerna daripada natrium diklofenak setelah 2 minggu pengobatan dalam hal keluhan nyeri abdomen atas dan kembung abdomen dengannilai kebermaknaan pengujian masing-masing sebesar 0,020 dan 0,037. Berdasarkan hasil penelitian ini diketahui meloxicam memiliki tolerabilitas saluran cerna lebih baik daripada natrium diklofenak setelah 2 minggu pengobatan. AbstractPerbedaan Tolerabilitas Meloxicam dengan Natrium Diklofenak terhadap Saluran Cerna pada Pasien Rawat Jalan di Poliklinik Penyakit Saraf Rumah Sakit Angkatan Laut Dr. Mintohardjo, Jakarta 2011. Non-steroidal anti-inflammatory drugs (NSAIDs are associated with a high incidence of

Preparation, structural analysis, and properties of tenoxicam cocrystals.

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Patel, Jagdishwar R; Carlton, Robert A; Needham, Thomas E; Chichester, Clinton O; Vogt, Frederick G

2012-10-15

Cocrystals of tenoxicam, a non-steroidal anti-inflammatory drug, are screened, prepared, and characterized in this study. Nine tenoxicam cocrystals were identified using solvent-drop grinding (SDG) techniques. Structural characterization was performed using powder X-ray diffraction (PXRD), differential scanning calorimetry, and multinuclear solid-state NMR (SSNMR). Thermal analysis, PXRD, and 1D SSNMR are used to detect solvates and phase mixtures encountered in SDG cocrystal screening. 2D SSNMR methods are then used to confirm cocrystal formation and determine structural aspects for selected cocrystals formed with saccharin, salicylic acid, succinic acid, and glycolic acid in comparison to Forms I and III of tenoxicam. Molecular association is demonstrated using cross-polarization heteronuclear dipolar correlation (CP-HETCOR) methods involving (1)H and (13)C nuclei. Short-range (1)H-(13)C CP-HETCOR and (1)H-(1)H double-quantum interactions between atoms of interest, including those engaged in hydrogen bonding, are used to reveal local aspects of the cocrystal structure. (15)N SSNMR is used to assess ionization state and the potential for zwitterionization in the selected cocrystals. The tenoxicam saccharin cocrystal was found to be similar in structure to a previously-reported cocrystal of piroxicam and saccharin. The four selected cocrystals yielded intrinsic dissolution rates that were similar or reduced relative to tenoxicam Form III. Copyright © 2012 Elsevier B.V. All rights reserved.

Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials

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Pajaree Sriuttha

2018-01-01

Full Text Available Background. Nonsteroidal anti-inflammatory drugs (NSAIDs are the most widely used medication in several countries, including Thailand. NSAIDs have been associated with hepatic side effects; however, the frequency of these side effects is uncertain. Aim of the Review. To systematically review published literature on randomized, controlled trials that assessed the risk of clinically significant hepatotoxicity associated with NSAIDs. Methods. Searches of bibliographic databases EMBASE, PubMed, and the Cochrane Library were conducted up to July 30, 2016, to identify randomized controlled trials of ibuprofen, naproxen, diclofenac, piroxicam, meloxicam, mefenamic acid, indomethacin, celecoxib, and etoricoxib in adults with any disease that provide information on hepatotoxicity outcomes. Results. Among the 698 studies, 18 studies met the selection criteria. However, only 8 studies regarding three NSAIDs (celecoxib, etoricoxib, and diclofenac demonstrated clinically significant hepatotoxic evidence based on hepatotoxicity justification criteria. Of all the hepatotoxicity events found from the above-mentioned three NSAIDs, diclofenac had the highest proportion, which ranged from 0.015 to 4.3 (×10−2, followed by celecoxib, which ranged from 0.13 to 0.38 (×10−2, and etoricoxib, which ranged from 0.005 to 0.930 (×10−2. Conclusion. Diclofenac had higher rates of hepatotoxic evidence compared to other NSAIDs. Hepatotoxic evidence is mostly demonstrated as aminotransferase elevation, while liver-related hospitalization or discontinuation was very low.

Unusual interleukin-1 and -6 expression in fetal cartilage is associated with placental abnormalities.

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Robert Klepacz

2010-06-01

Full Text Available Unusual expression of interleukin-1alpha, -1beta and -6 was previously found in the epiphyseal cartilage of rat fetuses prenatally exposed to various non-steroidal anti-inflammatory drugs (NSAID, i.e., ibuprofen, piroxicam, tolmetin and selective cyclooxygenase-2 inhibitor (DFU. The aim of the present study was to evaluate the role of placenta in such phenomenon. Morphology of the organ, thickness of basal and labyrinth layer, immunoexpression of COX isoenzymes were examined, and confronted with maternal biochemical data and fetal developmental parameters. Higher maternal urea level, as well as lower placental weight and labyrinth thickness were found in the group of fetuses who revealed expression of genes coded the selected interleukins, when compared with the xenobiotic-exposed pups without the selected genes expression and untreated control. A significant correlation between placental weight and maternal total protein or urea level was revealed. Histological changes like inflammatory infiltration and calcification were observed sporadically. Location and intensity of COX-1 staining was similar in all cases. However, more intense COX-2 staining for majority of cells of the basal zone and in dispersed giant cells of the labyrinth was found in inflamed organs. It could be concluded that abnormal expression of the selected interleukins is associated with low placental weight and decrease of its thickness, especially labyrinth zone, as well as with high maternal urea level.

Amtolmetin: A Reappraisal of NSAID with Gastroprotection

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Amit Garg

2016-01-01

Full Text Available Aim. To assess the gastrosparing effect of amtolmetin guacyl (AMG against other nonsteroidal anti-inflammatory drugs (NSAIDs in patients with osteo-/rheumatoid arthritis. Methods. A literature search was done in the electronic databases (PubMed, Google Scholar, Embase, and Scopus with key words “amtolmetin guacyl”, “amtolmetin”, and “arthritis”; filters were applied to obtain publications between 01-Jan-1985 and 01-Oct-2015, which were “clinical trials” in osteo-/rheumatoid arthritis patients and in “English language.” Studies were assessed using the Jadad criteria and trials with score ≥ 3 were included in the analysis to compare the safety and efficacy of AMG against other NSAIDs. Results. Search yielded 19 publications of which 3 were included for analysis. Baseline characteristics of patients were comparable between the AMG group and other NSAIDs (diclofenac, celecoxib, and piroxicam groups in all trials. Efficacy of AMG was similar to the other NSAIDs compared in the trials. The number of adverse events (AEs reported was similar between both the groups; however, severe AEs reported were significantly lower in the AMG group. Of note was the significant lower number of duodenal ulcers after treatment in the AMG group. Conclusions. AMG has efficacy similar to other NSAIDs and a safer gastrointestinal AE profile when compared to the other NSAIDs.

A Systematic Study of Molecular Interactions of Anionic Drugs with a Dimethylaminoethyl Methacrylate Copolymer Regarding Solubility Enhancement.

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Saal, Wiebke; Ross, Alfred; Wyttenbach, Nicole; Alsenz, Jochem; Kuentz, Martin

2017-04-03

The methacrylate-copolymer Eudragit EPO (EPO) has raised interest in solubility enhancement of anionic drugs. Effects on aqueous drug solubility at rather low polymer concentrations are barely known despite their importance upon dissolution and dilution of oral dosage forms. We provide evidence for substantial enhancement (factor 4-230) of aqueous solubility of poorly water-soluble anionic drugs induced by low (0.1-5% (w/w)) concentration of EPO for a panel of seven acidic crystalline drugs. Diffusion data (determined by 1 H nuclear magnetic resonance spectroscopy) indicate that the solubility increasing effect monitored by quantitative ultraperformance liquid chromatography was caused primarily by molecular API polymer interactions in the bulk liquid phase. Residual solid API remained unaltered as tested by X-ray powder diffraction. The solubility enhancement (SE) revealed a significant rank correlation (r Spearman = -0.83) with rDiff API , where SE and rDiff API are defined ratios of solubility and diffusion coefficient in the presence and absence of EPO. SE decreased in the order of indomethacin, mefenamic acid, warfarin, piroxicam, furosemide, bezafibrate, and tolbutamide. The solubilizing effect was attributed to both ionic and hydrophobic interactions between drugs and EPO. The excellent solubilizing properties of EPO are highly promising for pharmaceutical development, and the data set provides first steps toward an understanding of drug-excipient interaction mechanisms.

Multimodal non-surgical treatment of a feline tracheal adenocarcinoma

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Carolina Azevedo

2017-02-01

Full Text Available Case summary A 10-year-old, castrated male domestic shorthair cat presented with a 2–3 month history of weight loss, lethargy and coughing. Thoracic radiographs revealed a soft tissue opacity overlying the dorsal trachea from the first rib to second rib and the ventral aspect of the trachea extending from the second rib to approximately the fourth rib. CT confirmed a mass involving the dorsal, right lateral and ventral aspects of the trachea narrowing the lumen and extending from vertebra C7 through T4. Bronchoscopy revealed a partially circumferential irregular and multilobulated tracheal mass, which was biopsied. The histopathological diagnosis was tracheal adenocarcinoma. The cat was treated with a definitive course of external beam radiation therapy (RT; 3 Gy × 18, cytotoxic chemotherapy, a tyrosine kinase inhibitor and palliative RT. The cat remained asymptomatic for 2 months and the mass remained stable radiographically for 11 months after RT. Relevance and novel information With multimodal treatment the cat had a survival time of 755 days. Initial treatment included definitive RT, carboplatin and piroxicam, followed by toceranib phosphate and palliative RT when the mass recurred. This case report describes the first documented use of non-surgical treatment and long-term outcome of tracheal adenocarcinoma in a cat. This case report is an indication that prolonged survival can be achieved with multimodal therapy.

Cuantificación de glibenclamida en muestras de limpieza de equipos farmacéuticos mediante cromatografía líquida de alta resolución Quantification of glibenclamide in cleaning samples of pharmaceutical equipment through high performance liquid chromatography

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Alen Nils Baeza Fonte

2012-03-01

Full Text Available Objetivo: proponer un procedimiento analítico selectivo para la cuantificación de glibenclamida en muestras de limpieza de equipos farmacéuticos mediante cromatografía líquida de alta resolución. Métodos: la fase móvil consistió en una mezcla equivalente de volúmenes de acetonitrilo y solución amortiguadora KH2PO4 de concentración 0,037 mol/L a pH 5,25 y flujo 1,5 mL/min, en una columna Nucleosil 100 C8. La glibenclamida se inyectó con progesterona como estándar interno y empleando detector UV a una l= 230 nm. Resultados: el método resultó lineal en el intervalo de concentraciones de 0,4-150 mg/mL, teniendo como límites de detección y cuantificación 10 y 40 ng/mL respectivamente y siendo específico al analito en presencia del placebo, sus productos de degradación y a otros ingredientes farmacéuticamente activos. Se consideraron potenciales de interferencias para el método propuesto: captopril, clortalidona, dexametasona, digoxina, 8-cloroteofilina, difenhidramina HCl, fenobarbital, haloperidol, hidroclorotiazida, ácido fumárico, ketotifeno, metoclopramida HCl, piridoxina HCl, piroxicam, prednisona y nifedipino. Se identificaron: ibuprofeno, indometacina, trifluoperazina HCl, tioridazina HCl e imipramina HCl, como interferentes del procedimiento en concentraciones cercanas a 10 mg/mL. Conclusiones: el método desarrollado es sensible, rápido y especialmente selectivo para la evaluación de residuales del principio activo glibenclamida en equipos de producción de tabletas, empleando un muestreo por hisopado, y pudiera utilizarse potencialmente cuando exista sospecha de contaminación cruzada de glibenclamida con otros fármacos de los aquí descritos.Objective: to submit a selective analytical method for quantization of glibenclamide in cleaning samples of pharmaceutical equipment using high performance liquid chromatography. Methods: the mobile phase consisted of an equal mixing of acetonitrile/phosphate buffer KH2PO4

Safety of subcutaneous microinjections (mesotherapy) in musicians.

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Navarte, Danik Arana; Rosset-Llobet, Jaume

2011-06-01

Determine the safety and tolerance of mesotherapy as a technique for the treatment of musculoskeletal complaints in musicians. 67 patients (55.2% women) were subjected to a total of 267 mesotherapy sessions. A mesotherapy needle or normal needle was used randomly. The drugs employed were thiocolchicoside and diazepam as muscular relaxants, pentoxifylline or buflomedil as vasodilators, and piroxicam as an anti-inflammatory, as directed. A visual analogue scale was used to quantify the pain produced by the microinjections as well as the degree of immediate and midterm side effects as reported on a standard questionnaire. A mean of 155.5 microinjections were performed per session, of which 45.6% were perceived as painful by the patient with a mean severity of 4.3 out of 10. The pain reduced to 0.5 out of 10 after 24 hours. The most sensitive areas were the levator scapulae and splenius muscles. Systemic symptoms were reported by 5.99% of the musicians after the mesotherapy sessions (muscular weakness 1.5%, rash 1.5%, drowsiness 1.1% and itching 1.1%, being the most frequent). The mean severity of these symptoms was 2.77 out of 10. In all cases the symptoms had completely disappeared after 24 hours. No patient referred to signs of local or systemic infection. The application of drugs by means of subcutaneous injections (mesotherapy) in musicians is a technique that is safe, well tolerated, and without any severe complications.

Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis

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Gross, N.J.; Holloway, N.O.; Narine, K.R. (Medical Radiology Service, Hines VA Hospital, Maywood, IL (United States))

1991-09-01

Corticosteroids have previously been found to be protective against the mortality of radiation pneumonitis in mice, even when given well after lethal lung irradiation. The authors explored the possibility that this effect was due to their well-known anti-inflammatory actions by giving various nonsteroidal inhibitors of arachidonate metabolism to groups of mice that had received 19 Gy to the thorax (bilaterally). Treatments of four cyclooxygenase inhibitors, one lipoxygenase inhibitor, and one leukotriene receptor antagonist, given by various routes in various doses, were commenced 10 weeks after irradiation or sham irradiation and continued throughout the period when death from radiation pneumonitis occurs, 11-26 weeks after irradiation. Each of the treatments had the appropriate effect on arachidonate metabolism in the lungs as assessed by LTB4 and PGE2 levels in lung lavage fluid. The principal end point was mortality. The 5-lipoxygenase inhibitor diethylcarbamazine and the LTD4/LTE4 receptor antagonist LY 171883 markedly reduced mortality in dose-response fashion. The effects of cyclooxygenase inhibitors were divergent; piroxicam and ibuprofen were marginally protective, indomethacin in all doses accelerated mortality, and aspirin reduced mortality in a dose-response fashion. These results suggest that the protective effect of corticosteroids in radiation pneumonitis can be tentatively attributed to their anti-inflammatory actions, and that nonsteroidal anti-inflammatory agents, particularly those that affect lipoxygenase products, may offer equal or better protection than corticosteroids against mortality due to radiation pneumonitis.

Differential stimulation of luminol-enhanced chemiluminescence (CL) and arachidonic acid metabolism in rat peritoneal neutrophils

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Sturm, R.J.; Adams, L.M.; Cullinan, C.A.; Berkenkopf, J.W.; Weichman, B.M.

1986-03-05

Phorbol 12-myristate, 13-acetate (PMA) induced the production of radical oxygen species (ROS) from rat peritoneal neutrophils as assessed by CL. ROS generation occurred in a time- (maximum at 13.5 min) and dose- (concentration range of 1.7-498 nM) related fashion. However, 166 nM PMA did not induce either cyclooxygenase (CO) or lipoxygenase (LPO) product formation by 20 min post-stimulation. Conversely, A23187, at concentrations between 0.1 and 10 ..mu..M, stimulated both pathways of arachidonic acid metabolism, but had little or no effect upon ROS production. When suboptimal concentrations of PMA (5.5 nM) and A23187 (0.1-1 ..mu..M) were coincubated with the neutrophils, a synergistic ROS response was elicited. However, arachidonic acid metabolism in the presence of PMA was unchanged relative to A12187 alone. Nordihydroguaiaretic acid (NDGA) inhibited both PMA-induced CL (IC/sub 50/ = 0.9 ..mu..M) and A23187-induced arachidonic acid metabolism (IC/sub 50/ = 1.7 ..mu..M and 6.0 ..mu..M for LPO and CO, respectively). The mixed LPO-CO inhibitor, BW755C, behaved in a qualitatively similar manner to NDGA, whereas the CO inhibitors, indomethacin, piroxicam and naproxen had no inhibitory effect on ROS generation at concentrations as high as 100 ..mu..M. These results suggest that NDGA and BW755C may inhibit CL and arachidonic acid metabolism by distinct mechanisms in rat neutrophils.

Hierarchically structured self-supported latex films for flexible and semi-transparent electronics

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Määttänen, Anni; Ihalainen, Petri; Törngren, Björn; Rosqvist, Emil; Pesonen, Markus; Peltonen, Jouko

2016-02-01

Different length scale alterations in topography, surface texture, and symmetry are known to evoke diverse cell behavior, including adhesion, orientation, motility, cytoskeletal condensation, and modulation of intracellular signaling pathways. In this work, self-supported latex films with well-defined isotropic/anisotropic surface features and hierarchical morphologies were fabricated by a peel-off process from different template surfaces. In addition, the latex films were used as substrates for evaporated ultrathin gold films with nominal thicknesses of 10 and 20 nm. Optical properties and topography of the samples were characterized using UV-vis spectroscopy and Atomic Force Microscopy (AFM) measurements, respectively. The latex films showed high-level transmittance of visible light, enabling the fabrication of semi-transparent gold electrodes. Electrochemical impedance spectroscopy (EIS) measurements were carried out for a number of days to investigate the long-term stability of the electrodes. The effect of 1-octadecanethiol (ODT) and HS(CH2)11OH (MuOH) thiolation and protein (human serum albumin, HSA) adsorption on the impedance and capacitance was studied. In addition, cyclic voltammetry (CV) measurements were carried out to determine active medicinal components, i.e., caffeic acid with interesting biological activities and poorly water-soluble anti-inflammatory drug, piroxicam. The results show that the fabrication procedure presented in this study enables the formation of platforms with hierarchical morphologies for multimodal (optical and electrical) real-time monitoring of length-scale-dependent biomaterial-surface interactions.

NSAID Antinociception Measured in a Chemical and a Thermal Assay in Mice

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HF Miranda

2001-01-01

Full Text Available The antinociceptive activity of several nonsteroidal anti-inflammatory drugs (NSAIDs that were administered either intraperitoneally or intrathecally was assessed in mice by two algesiometric tests. The first was the writhing test, which assessed the abdominal constrictions that were induced by intraperitoneal acetic acid (a chemical test, and the second was the tail flick test, which measured pain responses to heat stimuli. The corresponding effective doses and their relative potencies were compared because these tests use different nociceptive stimuli with different transmission pathways. The intraperitoneal and intrathecal dose-response curves for the antinociception induced by every NSAID that was tested were parallel in the writhing test. In the tail flick test, however, only the intraperitoneal and intrathecal dose-response curves for ketoprofen, piroxicam, naproxen, nimesulide, paracetamol and diclofenac were parallel. The results obtained in this study confirm that NSAIDs possess different abilities to induce inhibition of cyclooxygenase, and they can be indirectly assessed by their different antinociceptive activities, depending on the algesiometric assays that are used. The antinociception of most NSAIDs might involve central mechanisms. The findings demonstrate the increasing importance of the spinal cord in processing and modulating nociceptive input, because intrathecal administration of NSAIDs is always more effective (in terms of potency than systemic administration; thus, the antinociceptive efficacy of NSAIDs strongly depends on the algesiometric assay that is used and on the type of the nociceptive stimulus to which the test subject is exposed.

Asymptomatic prostatic inflammation in men with clinical BPH and erectile dysfunction affects the positive predictive value of prostate-specific antigen.

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Agnihotri, Shalini; Mittal, Rama Devi; Kapoor, Rakesh; Mandhani, Anil

2014-10-01

To test the hypothesis that sexual dysfunction in elderly men with benign prostatic hyperplasia leads to prostatic inflammation, diagnosed by prostatic fluid interleukin-8 (IL-8), which lowers the positive predictive value of prostate-specific antigen (PSA). Overall, 160 men with lower urinary tract symptoms between 50 and 75 years of age with an elevated PSA level of more than 4 ng/ml with normal digital rectal examination and 50 age-matched controls with normal PSA level were prospectively evaluated for prostatic fluid IL-8 levels. Erectile dysfunction was measured by self-administered questionnaire of the Sexual Health Inventory for Men. Total and free serum PSA levels and IL-8 in prostatic fluid were measured 6 to 8 weeks after a course of 400mg of ofloxacin and 20mg of piroxicam given daily for 2 weeks. Transrectal ultrasonography-guided biopsy was done only when PSA level did not decrease less than 4 ng/ml. Mean ages of patients and controls were 63.18 (standard deviation [SD]±7.10) and 60.18 (SD+6.02) years, respectively. Mean concentration of IL-8 in prostatic fluid of the patients was significantly higher, i.e., 6678 pg/ml (SD±1985.7) than in control, i.e., 1543 pg/ml (SD±375.7) (Pprostatic hyperplasia and erectile dysfunction had significant inflammation of the prostate to cause spurious rise in PSA level resulting in an unnecessary biopsy. Copyright © 2014 Elsevier Inc. All rights reserved.

Commentary on "Asymptomatic prostatic inflammation in men with clinical BPH and erectile dysfunction affects the positive predictive value of prostate-specific antigen." Agnihotri S, Mittal RD, Kapoor R, Mandhani A, Department of Urology & Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.: Urol Oncol 2014; [Epub ahead of print]. doi: 10.1016/j.urolonc.2014.03.004.

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Pu, Chunxiao; Wang, Jia; Wei, Qiang; Han, Ping

2015-02-01

To test the hypothesis that sexual dysfunction in elderly men with benign prostatic hyperplasia leads to prostatic inflammation, diagnosed by prostatic fluid interleukin-8 (IL-8), which lowers the positive predictive value of prostate-specific antigen (PSA). Overall, 160 men with lower urinary tract symptoms between 50 and 75 years of age with an elevated PSA level of more than 4ng/ml with normal digital rectal examination and 50 age-matched controls with normal PSA level were prospectively evaluated for prostatic fluid IL-8 levels. Erectile dysfunction was measured by self-administered questionnaire of the Sexual Health Inventory for Men. Total and free serum PSA levels and IL-8 in prostatic fluid were measured 6 to 8 weeks after a course of 400mg of ofloxacin and 20mg of piroxicam given daily for 2 weeks. Transrectal ultrasonography-guided biopsy was done only when PSA level did not decrease less than 4ng/ml. Mean ages of patients and controls were 63.18 (standard deviation [SD]±7.10) and 60.18 (SD+6.02) years, respectively. Mean concentration of IL-8 in prostatic fluid of the patients was significantly higher, i.e., 6,678pg/ml (SD±1,985.7) than in control, i.e., 1,543pg/ml (SD±375.7) (Pprostatic hyperplasia and erectile dysfunction had significant inflammation of the prostate to cause spurious rise in PSA level resulting in an unnecessary biopsy. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of solvent evaporation rate and formulation factors on solid dispersion physical stability.

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Wu, Jian X; Yang, Mingshi; Berg, Frans van den; Pajander, Jari; Rades, Thomas; Rantanen, Jukka

2011-12-18

New chemical entities (NCEs) often show poor water solubility necessitating solid dispersion formulation. The aim of the current study is to employ design of experiments in investigating the influence of one critical process factor (solvent evaporation rate) and two formulation factors (PVP:piroxicam ratio (PVP:PRX) and PVP molecular weight (P(MW))) on the physical stability of PRX solid dispersion prepared by the solvent evaporation method. The results showed the rank order of an increase in factors contributing to a decrease in the extent of PRX nucleation being evaporation rate>PVP:PRX>P(MW). The same rank order was found for the decrease in the extent of PRX crystal growth in PVP matrices from day 0 up to day 12. However, after 12days the rank became PVP:PRX>evaporation rate>P(MW). The effects of an increase in evaporation rate and PVP:PRX ratio in stabilizing PRX were of the same order of magnitude, while the effect from P(MW) was much smaller. The findings were confirmed by XRPD. FT-IR showed that PRX recrystallization in the PVP matrix followed Ostwald's step rule, and an increase in the three factors all led to increased hydrogen bonding interaction between PRX and PVP. The present study showed the applicability of the Quality by Design approach in solid dispersion research, and highlights the need for multifactorial analysis. Copyright © 2011 Elsevier B.V. All rights reserved.

UPPER GASTROINTESTINAL TRACT HEMORRHAGE AND NONSTEROIDALANTIINFLAMMATORY DRUGS (NSAIDs – A 5-YEAR PROSPECTIVE STUDY

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Pavel Skok

2002-03-01

Full Text Available Background. Adverse effects of nonsteroidal antiinflammatory drugs (NSAIDs are a common cause of digestive tract hemorrhage.Study aims. The purpose of the study was to ascertain the percent of patients taking NSAIDs with upper digestive tract hemorrhage.Type of study. Prospective, analytical.Patients and methods. The study includes patients in which urgent endoscopic investigations of the upper digestive tract were carried out due to gastrointestinal hemorrhage between 1 January 1994 and 31 December 1998.Results. 3366 patients were investigated: 1222 women and 2144 men; the average age of our patients was 57.5 years (SD ± 17.1, a 2–97 year span. In 2905 patients (86.3% the source of bleeding was confirmed in the upper gastrointestinal tract. Among our patients 55% were aged over 60 years, 26.7% were older than 80 years. Sequelae of peptic ulcer disease were the most significant cause of gastrointestinal hemorrhage, in 47.7% of our patients (1387/2905. In the last week prior to bleeding, 19% of patients (552/2905 were taking regularly NSAIDs, corticosteroids, salycilates or anticoagulant therapy at least in single daily dose. The majority of patients, 94.5%, were taking NSAIDs or salycilates. Among NSAIDs they were taking most often ketoprofen, diclofenac or naproxen/ naproxen natrium, less often ibuprofen, nabumeton, etodolac or piroxicam.Conclusions. Upper digestive tract hemorrhage is a serious complication of NSAIDs medication, particularly in older patients

Analisis Adulterasi Jamu Pegal Linu yang Diperoleh dari Pasar di Jakarta dan Sekitarnya (Analysis of Adulterated Jamu Pegal Linu Obtained from the Market in Jakarta

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Retno Gitawati

2014-04-01

Full Text Available Background: “Jamu Pegal Linu” (traditional Indonesian herb for rheumatoid and gouty arthritis is one of the mostpopular jamu products manufactured and widely consumed in the community. Despite the claims that they are made ofnatural herbs, these kinds of jamu are susceptible for being counterfeited and adulterated with drugs that is potentiallyharmful for health. The aim of this study was to identify medicinal adulteration in jamu pegal linu products obtained from the market in Jakarta and surroundings. Method: This study was an experimental laboratory in a cross-sectional design. About 450 samples of jamu pegal linu products were randomly chosen, and the products with different brands wereanalyzed for medicinal adulteration using a thin layer chromatography (TLC method. Product labels of the adulterated jamu were also analyzed for the appropriateness of the product information. Results: Out of the 114 brands of jamu pegal linu analyzed, 52 samples (45.6% were positive for medicinal. The medicinal types detected were paracetamol (30.7%, phenylbutazone (20.4%, piroxicam (7.1% and mefenamic acid (3.5%. Two samples of jamu has been contaminated with molds and found damp. Of the 52 samples positive medicinal, 92.3% include the registration number and only 30.8% include the expiration date in the product labels. About 44.2% include the name of ingredients compositions written incorrectly in the labels. Conclusion: A. limited numbers of Jamu pegal linu products adulterated with medicinal still existed in the market.

Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis

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Gross, N.J.; Holloway, N.O.; Narine, K.R.

1991-01-01

Corticosteroids have previously been found to be protective against the mortality of radiation pneumonitis in mice, even when given well after lethal lung irradiation. The authors explored the possibility that this effect was due to their well-known anti-inflammatory actions by giving various nonsteroidal inhibitors of arachidonate metabolism to groups of mice that had received 19 Gy to the thorax (bilaterally). Treatments of four cyclooxygenase inhibitors, one lipoxygenase inhibitor, and one leukotriene receptor antagonist, given by various routes in various doses, were commenced 10 weeks after irradiation or sham irradiation and continued throughout the period when death from radiation pneumonitis occurs, 11-26 weeks after irradiation. Each of the treatments had the appropriate effect on arachidonate metabolism in the lungs as assessed by LTB4 and PGE2 levels in lung lavage fluid. The principal end point was mortality. The 5-lipoxygenase inhibitor diethylcarbamazine and the LTD4/LTE4 receptor antagonist LY 171883 markedly reduced mortality in dose-response fashion. The effects of cyclooxygenase inhibitors were divergent; piroxicam and ibuprofen were marginally protective, indomethacin in all doses accelerated mortality, and aspirin reduced mortality in a dose-response fashion. These results suggest that the protective effect of corticosteroids in radiation pneumonitis can be tentatively attributed to their anti-inflammatory actions, and that nonsteroidal anti-inflammatory agents, particularly those that affect lipoxygenase products, may offer equal or better protection than corticosteroids against mortality due to radiation pneumonitis

Evaluation of the Effect of Mesotherapy in the Management of Osteoarthritis-Related Pain in a Police Working Dog Using the Canine Brief Pain Inventory.

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Alves, João Carlos; Santos, Ana Margarida

2017-03-01

A 9-year-old, 33.4kg (73.63Lb) male entire drug detection Labrador Retriever Dog was presented with an history of constant lameness from the right thoracic limb, aggravated with exercise and work. Clinical examination revealed mild signs of pain on the manipulation of the elbow joint, with reduced range of motion on the end feel of joint flexion and extension and crepitation. Radiographic examination of the right elbow joint revealed severe, chronic osteoarthritis, with osteophyte formation on the humeral epicondyles and articular margin of the distomedial humerus, with a narrowed joint space, and osteophytes on the proximal radius, proximomedial ulna, and anconeal process. A solution comprised of a combination of lidocaine, thiocolchicoside, and piroxicam was prepared and applied around the right elbow joint. The animal was rested for 3 days and normal work load was introduced over a 5-day period. The CPBI was completed by the trainer before treatment (T0), 14 days (T1), 1 (T2), 2 (T3), 3 (T4), 4 (T5), 5 (T6), and 6 (T7) months after treatment. Following the mesotherapy session, pain score results consistently declined until the 3-month evaluation moment. At the 6-month follow-up evaluation, values have risen to near baseline values. No side effects were recorded. Mesotherapy produced significant reduction of pain score results, as measure by the CBPI, and may be a promising treatment option for canine osteoarthritis-related pain. Further studies are required. Copyright © 2017 Elsevier Inc. All rights reserved.

Determining the Molecular Pathways Underlying the Protective Effect of Non-Steroidal Anti-Inflammatory Drugs for Alzheimer's Disease: A Bioinformatics Approach

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Alejo J Nevado-Holgado

Full Text Available Alzheimer's disease (AD represents a substantial unmet need, due to increasing prevalence in an ageing society and the absence of a disease modifying therapy. Epidemiological evidence shows a protective effect of non steroidal anti inflammatory (NSAID drugs, and genome wide association studies (GWAS show consistent linkage to inflammatory pathways; both observations suggesting anti-inflammatory compounds might be effective in AD therapy although clinical trials to date have not been positive.In this study, we use pathway enrichment and fuzzy logic to identify pathways (KEGG database simultaneously affected in both AD and by NSAIDs (Sulindac, Piroxicam, Paracetamol, Naproxen, Nabumetone, Ketoprofen, Diclofenac and Aspirin. Gene expression signatures were derived for disease from both blood (n = 344 and post-mortem brain (n = 690, and for drugs from immortalised human cell lines exposed to drugs of interest as part of the Connectivity Map platform. Using this novel approach to combine datasets we find striking overlap between AD gene expression in blood and NSAID induced changes in KEGG pathways of Ribosome and Oxidative Phosphorylation. No overlap was found in non NSAID comparison drugs. In brain we find little such overlap, although Oxidative Phosphorylation approaches our pre-specified significance level.These findings suggest that NSAIDs might have a mode of action beyond inflammation and moreover that their therapeutic effects might be mediated in particular by alteration of Oxidative Phosphorylation and possibly the Ribosome pathway. Mining of such datasets might prove increasingly productive as they increase in size and richness. Keywords: Alzheimer's disease, NSAID, Inflammation, Fuzzy logic, Ribosome

Neostigmine interactions with non steroidal anti-inflammatory drugs.

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Miranda, Hugo F; Sierralta, Fernando; Pinardi, Gianni

2002-04-01

1. The common mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of the enzyme cyclo-oxygenase (COX), however, this inhibition is not enough to completely account for the efficacy of these agents in several models of acute pain. 2. It has been demonstrated that cholinergic agents can induce antinociception, but the nature of the interaction between these agents and NSAIDs drugs has not been studied. The present work evaluates, by isobolographic analysis, the interactions between the cholinergic indirect agonist neostigmine (NEO) and NSAIDs drugs, using a chemical algesiometric test. 3. Intraperitoneal (i.p.) or intrathecal (i.t.) administration of NEO and of the different NSAIDs produced dose-dependent antinociception in the acetic acid writhing test of the mouse. 4. The i.p. or i.t. co-administration of fixed ratios of ED(50) fractions of NSAIDs and NEO, resulted to be synergistic or supra-additive for the combinations ketoprofen (KETO) and NEO, paracetamol (PARA) and NEO) and diclofenac (DICLO) and NEO administered i.p. However, the same combinations administered i.t. were only additive. In addition, the combinations meloxicam (MELO) and NEO and piroxicam (PIRO) and NEO, administered either i.p. or i.t., were additive. 5. The results suggest that the co-administration of NEO with some NSAIDs (e.g. KETO, PARA or DICLO) resulted in a synergistic interaction, which may provide evidence of supraspinal antinociception modulation by the increased acetylcholine concentration in the synaptic cleft of cholinergic interneurons. The interaction obtained between neostigmine and the NSAIDs could carry important clinical implications.

Effects of NSAIDs on the metabolism of sulphated glycosaminoglycans in healthy and (post) arthritic murine articular cartilage.

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de Vries, B J; van den Berg, W B; Vitters, E; van de Putte, L B

1988-01-01

Several non-steroidal anti-inflammatory drugs (NSAIDs) were studied for their effects on normal and damaged murine articular cartilage, both in vitro and in vivo. In vitro, in the absence of serum, sodium salicylate caused significant suppression of 35S-glycosaminoglycan (GAG) synthesis, whereas tiaprofenic acid, piroxicam, prednisolone sodium phosphate and several other NSAIDs were without effect. Trypsin-mediated proteoglycan depletion did not change the susceptibility of the articular chondrocyte to these drugs. Similarly, no enhancement of drug effect was seen when arthritic cartilage was taken from an acutely inflamed joint, and prenisolone sodium phosphate even seemed to diminish inflammation-mediated suppression of 35S-GAG synthesis. The short term in vivo effects of some of the drugs were tested in mice with unilateral zymosan-induced arthritis. At day 1 after arthritis induction, in vivo 35S-GAG synthesis by the cartilage of the arthritic joint was decreased to 63%. Only sodium salicylate suppressed in vivo 35S-GAG synthesis in the healthy and arthritic joint to the same extent in both. At day 28, GAG synthesis in the postarthritic joint was enhanced to 160%. This type of cartilage appeared to be more susceptible to drug effects, since all drugs tested showed clear suppression of the augmented GAG production in vivo. Finally, in vivo drug effects were tested on normal and enhanced 35S-GAG degradation, the latter in the zymosan-induced arthritic joint. Both tiaprofenic acid and prednisolone sodium phosphate appeared to suppress degradation in healthy and, to some extent, in arthritic cartilage.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of inhibition of myeloperoxidase by anti-inflammatory drugs.

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Kettle, A J; Winterbourn, C C

1991-05-15

Hypochlorous acid (HOCl) is the most powerful oxidant produced by human neutrophils, and should therefore be expected to contribute to the damage caused by these inflammatory cells. It is produced from H2O2 and Cl- by the heme enzyme myeloperoxidase (MPO). We used a H2O2-electrode to assess the ability of a variety of anti-inflammatory drugs to inhibit conversion of H2O2 to HOCl. Dapsone, mefenamic acid, sulfapyridine, quinacrine, primaquine and aminopyrine were potent inhibitors, giving 50% inhibition of the initial rate of H2O2 loss at concentrations of about 1 microM or less. Phenylbutazone, piroxicam, salicylate, olsalazine and sulfasalazine were also effective inhibitors. Spectral investigations showed that the inhibitors acted by promoting the formation of compound II, which is an inactive redox intermediate of MPO. Ascorbate reversed inhibition by reducing compound II back to the active enzyme. The characteristic properties that allowed the drugs to inhibit MPO reversibly were ascertained by determining the inhibitory capacity of related phenols and anilines. Inhibition increased as substituents on the aromatic ring became more electron withdrawing, until an optimum reduction potential was reached. Beyond this optimum, their inhibitory capacity declined. The best inhibitor was 4-bromoaniline which had an I50 of 45 nM. An optimum reduction potential enables inhibitors to reduce MPO to compound II, but prevents them from reducing compound II back to the active enzyme. Exploitation of this optimum reduction potential will help in targeting drugs against HOCl-dependent tissue damage.

Effects of non-steroidal anti-inflammatory drugs on cyanobacteria and algae in laboratory strains and in natural algal assemblages.

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Bácsi, István; B-Béres, Viktória; Kókai, Zsuzsanna; Gonda, Sándor; Novák, Zoltán; Nagy, Sándor Alex; Vasas, Gábor

2016-05-01

In recent years measurable concentrations of non-steroidal anti-inflammatory drugs (NSAIDs) have been shown in the aquatic environment as a result of increasing human consumption. Effects of five frequently used non-steroidal anti-inflammatory drugs (diclofenac, diflunisal, ibuprofen, mefenamic acid and piroxicam in 0.1 mg ml(-1) concentration) in batch cultures of cyanobacteria (Synechococcus elongatus, Microcystis aeruginosa, Cylindrospermopsis raciborskii), and eukaryotic algae (Desmodesmus communis, Haematococcus pluvialis, Cryptomonas ovata) were studied. Furthermore, the effects of the same concentrations of NSAIDs were investigated in natural algal assemblages in microcosms. According to the changes of chlorophyll-a content, unicellular cyanobacteria seemed to be more tolerant to NSAIDs than eukaryotic algae in laboratory experiments. Growth of eukaryotic algae was reduced by all drugs, the cryptomonad C. ovata was the most sensitive to NSAIDs, while the flagellated green alga H. pluvialis was more sensitive than the non-motile green alga D. communis. NSAID treatments had weaker impact in the natural assemblages dominated by cyanobacteria than in the ones dominated by eukaryotic algae, confirming the results of laboratory experiments. Diversity and number of functional groups did not change notably in cyanobacteria dominated assemblages, while they decreased significantly in eukaryotic algae dominated ones compared to controls. The results highlight that cyanobacteria (especially unicellular ones) are less sensitive to the studied, mostly hardly degradable NSAIDs, which suggest that their accumulation in water bodies may contribute to the expansion of cyanobacterial mass productions in appropriate environmental circumstances by pushing back eukaryotic algae. Thus, these contaminants require special attention during wastewater treatment and monitoring of surface waters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Laboratory monitoring of patients treated with antihypertensive drugs and newly exposed to non steroidal anti-inflammatory drugs: a cohort study.

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Jean-Pascal Fournier

Full Text Available BACKGROUND: Drug-Drug Interactions between Non Steroidal Anti-Inflammatory Drugs (NSAIDs and Angiotensin Converting Enzyme Inhibitors (ACEIs, Angiotensin Receptor Blocker (ARBs or diuretics can lead to renal failure and hyperkalemia. Thus, monitoring of serum creatinine and potassium is recommended when a first dispensing of NSAID occur in patients treated with these drugs. METHODS: We conducted a pharmacoepidemiological retrospective cohort study using data from the French Health Insurance Reimbursement Database to evaluate the proportion of serum creatinine and potassium laboratory monitoring in patients treated with ACEI, ARB or diuretic and receiving a first dispensing of NSAID. We described the first dispensing of NSAID among 3,500 patients of a 4-year cohort (6,633 patients treated with antihypertensive drugs and analyzed serum creatinine and potassium laboratory monitoring within the 3 weeks after the first NSAID dispensing. RESULTS: General Practitioners were the most frequent prescribers of NSAIDs (85.5%, 95% CI: 84.3-86.6. The more commonly prescribed NSAIDs were ibuprofen (20%, ketoprofen (15%, diclofenac (15% and piroxicam (12%. Serum creatinine and potassium monitoring was 10.7% (95% CI: 9.5-11.8 in patients treated by ACEIs, ARBs or diuretics. Overall, monitoring was more frequently performed to women aged over 60, treated with digoxin or glucose lowering drugs, but not to patients treated with ACEIs, ARBs or diuretics. Monitoring was more frequent when NSAIDs' prescribers were cardiologists or anesthesiologists. CONCLUSION: Monitoring of serum creatinine and potassium of patients treated with ACEIs, ARBs or diuretics and receiving a first NSAID dispensing is insufficiently performed and needs to be reinforced through specific interventions.

Optimal management of orthodontic pain

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Topolski F

2018-03-01

Full Text Available Francielle Topolski,1 Alexandre Moro,1,2 Gisele Maria Correr,3 Sasha Cristina Schimim1 1Department of Orthodontics, Positivo University, Curitiba, Paraná, Brazil; 2Department of Orthodontics, Federal University of Paraná, Curitiba, Paraná, Brazil; 3Department of Restorative Dentistry, Positivo University, Curitiba, Paraná, Brazil Abstract: Pain is an undesirable side effect of orthodontic tooth movement, which causes many patients to give up orthodontic treatment or avoid it altogether. The aim of this study was to investigate, through an analysis of the scientific literature, the best method for managing orthodontic pain. The methodological aspects involved careful definition of keywords and diligent search in databases of scientific articles published in the English language, without any restriction of publication date. We recovered 1281 articles. After the filtering and classification of these articles, 56 randomized clinical trials were selected. Of these, 19 evaluated the effects of different types of drugs for the control of orthodontic pain, 16 evaluated the effects of low-level laser therapy on orthodontic pain, and 21 evaluated other methods of pain control. Drugs reported as effective in orthodontic pain control included ibuprofen, paracetamol, naproxen sodium, aspirin, etoricoxib, meloxicam, piroxicam, and tenoxicam. Most studies report favorable outcomes in terms of alleviation of orthodontic pain with the use of low-level laser therapy. Nevertheless, we noticed that there is no consensus, both for the drug and for laser therapy, on the doses and clinical protocols most appropriate for orthodontic pain management. Alternative methods for orthodontic pain control can also broaden the clinician’s range of options in the search for better patient care. Keywords: tooth movement, pain control, drug therapy, laser therapy

The short-circuit current of the ileum, but not the colon, is altered in the streptozotocin diabetic rat.

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Forrest, Abigail; Makwana, Rajesh; Parsons, Mike

2006-02-01

Ion transport in control and streptozotocin-diabetic rat colon and ileum was studied using the Ussing chamber technique. No differences were observed between control and diabetic colonic mucosal short-circuit current under either basal or carbachol (100 nmol/L-1 micromol/L)-stimulated or prostaglandin E2 (100 nmol/L-1 micromol/L)-stimulated conditions. Similarly to colonic tissues, no differences in the short circuit current in either carbachol-stimulated or prostaglandin E2-stimulated tissues were observed between control and diabetic ileal mucosa. The basal diabetic ileal short circuit current (99.58 +/- 22.67 microA) was significantly greater than that of control ileal tissues (29.67 +/- 4.45 microA). This difference was abolished by the sodium-glucose-cotransporter inhibitor, phloridzin (50 micromol/L) (118.00 +/- 28.09 microA vs. 25.60 +/- 4.59 microA) and was also prevented by the replacement of glucose with mannitol in the buffer bathing the apical side of the tissue (control: 17.05 +/- 5.85 microA vs. 17.90 +/- 3.10 microA). Acetazolamide (450 micromol/L; a carbonic anhydrase inhibitor), amiloride, and bumetanide (100 micromol/L each; Na+-channel blockers), piroxicam (50 micromol/L; a COX1 cyclooxygenase inhibitor), and ouabain (1 mmol/L; a K+ transport inhibitor) had no effect on the basal short circuit current of either control or diabetic ileal tissues. This indicated that the alteration in the basal short circuit current of diabetic ileal tissues was due to a change in cellular glucose transport, whereas the evoked changes in short circuit current were unaffected by the diabetic state.

Influence of standard and novel LTB4 analogs on human neutrophil chemotaxis measured by the multiwell cap assay.

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Psychoyos, S; Uziel-Fusi, S; Bhagwat, S; Morrissey, M M

1989-11-30

Standard and novel LTB4 analogs were tested for neutrophil chemoattractant activity using the multiwell cap assay (Evans et al. (1986) Biosc. Rep. 6, 1041). The assay uses disposable equipment and measures chemotaxis by the number of cells able to migrate across the full thickness of cellulose nitrate filters. Under standard conditions (90 min incubation at 37 degrees C in buffer containing 2% bovine albumin), LTB4 and 6-cis-LTB1 had EC50 values of 3.5 and 15,000 nM, respectively. 20-hydroxy-LTB4 was equipotent with LTB4 and exhibited a similar biphasic chemotactic response, however, only one third of the number of cells migrated through the filter. 20-carboxy-LTB4 was inactive up to 1,000 nM. 5-desoxy-((6,7)-cis-cyclopropyl)-LTB2, (6,7)-benzo-LTB2 and 5-desoxy-(8,10)-LTB2 had EC50 values of 11,300, 50,000 and 84,000 nM, respectively. Checkerboard analysis indicated a chemokinetic component of 42% for LTB4 at a concentration causing peak chemotaxis. Reduction of albumin in the buffer to 0.5% increased the apparent potencies of LTB4 and 6-cis-LTB1 five-fold. Since LTB4 is a mediator of inflammation, various anti-inflammatory agents were tested at peak concentrations observed in vivo for in vitro inhibition of LTB4-stimulated chemotaxis in the presence of 0.5% albumin. Under the conditions of the assay, chloroquine diphosphate, dexamethasone, indomethacin, penicillamine, piroxicam and diclofenac sodium were inactive; gold sodium thiomalate was inhibitory (IC50 = 20 microM).

[A rare side effect of mesotherapy: Nicolau syndrome].

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Zaragoza, J; Delaplace, M; Benamara, M; Estève, E

2013-11-01

Nicolau's livedoid dermatitis is associated with drug-induced embolism in the cutaneous arterial bed, generally as a result of accidental intra-arterial injection. Herein, we report a case that is somewhat surprising because of its late onset following mesotherapy injections. A 53-year-old man, with a history solely of tendinopathy for which he underwent mesotherapy sessions, consulted for livedoid lesions of the front of the knee with central necrosis. History-taking revealed a final course of mesotherapy three weeks earlier for patellar tendinitis below the left kneecap; intradermal injection of procaine and piroxicam had been unusually and intensely painful. The remainder of the clinical examination revealed additional livedoid lesions on the outside of the left ankle as well as purpuric lesions on the pads of the toes on the left foot. Laboratory tests revealed nothing of note. Skin biopsies of the livedoid circumference of the lesion showed arteriolar emboli of an amorphous material within the dermis obliterating the arteriolar lumen. The clinical appearance of skin lesions after mesotherapy led us to a diagnosis of Nicolau livedoid dermatitis. Nicolau dermatitis is a rare skin complication described as occurring mainly as a result of intramuscular injections. The reported case is special because it comprises Nicolau dermatitis arising out of a session of mesotherapy employing an intradermal injection. However, there are only very few cases in which subcutaneous injections have induced Nicolau dermatitis. The pathophysiology is not well known, but several mechanisms are involved: arterial ischaemia by vasospasm or thrombosis. In this case, the semiotic appearance of the lesions and histological analysis militate in favour of accidental injection of a skin product into an arteriole, resulting in obliteration of the latter. Mesotherapy can induce Nicolau dermatitis. Copyright © 2013. Published by Elsevier Masson SAS.

Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

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Nadanaciva, Sashi [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States); Aleo, Michael D. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Strock, Christopher J. [Cyprotex US, Watertown, MA 02472 (United States); Stedman, Donald B. [Drug Safety Research and Development, Pfizer Inc., Groton, CT 06340 (United States); Wang, Huijun [Computational Sciences, Pfizer Inc., Groton, CT 06340 (United States); Will, Yvonne, E-mail: yvonne.will@pfizer.com [Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer, Inc., Groton, CT 06340 (United States)

2013-10-15

To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary.

Hierarchically structured self-supported latex films for flexible and semi-transparent electronics

International Nuclear Information System (INIS)

Määttänen, Anni; Ihalainen, Petri; Törngren, Björn; Rosqvist, Emil; Pesonen, Markus; Peltonen, Jouko

2016-01-01

Graphical abstract: - Highlights: • Transparent self-supported latex films were fabricated by a peel-off process. • Various template substrates were used for creating e.g. hierarchically structured latex films. • Ultra-thin and semi-transparent conductive gold electrodes were evaporated on the latex films.Electrochemical experiments were carried out to verify the applicability of the electrodes. - Abstract: Different length scale alterations in topography, surface texture, and symmetry are known to evoke diverse cell behavior, including adhesion, orientation, motility, cytoskeletal condensation, and modulation of intracellular signaling pathways. In this work, self-supported latex films with well-defined isotropic/anisotropic surface features and hierarchical morphologies were fabricated by a peel-off process from different template surfaces. In addition, the latex films were used as substrates for evaporated ultrathin gold films with nominal thicknesses of 10 and 20 nm. Optical properties and topography of the samples were characterized using UV–vis spectroscopy and Atomic Force Microscopy (AFM) measurements, respectively. The latex films showed high-level transmittance of visible light, enabling the fabrication of semi-transparent gold electrodes. Electrochemical impedance spectroscopy (EIS) measurements were carried out for a number of days to investigate the long-term stability of the electrodes. The effect of 1-octadecanethiol (ODT) and HS(CH_2)_1_1OH (MuOH) thiolation and protein (human serum albumin, HSA) adsorption on the impedance and capacitance was studied. In addition, cyclic voltammetry (CV) measurements were carried out to determine active medicinal components, i.e., caffeic acid with interesting biological activities and poorly water-soluble anti-inflammatory drug, piroxicam. The results show that the fabrication procedure presented in this study enables the formation of platforms with hierarchical morphologies for multimodal (optical and

Hierarchically structured self-supported latex films for flexible and semi-transparent electronics

Energy Technology Data Exchange (ETDEWEB)

Määttänen, Anni, E-mail: anni.maattanen@abo.fi [Laboratory of Physical Chemistry, Faculty of Science and Engineering, Center for Functional Materials, Åbo Akademi University, Porthaninkatu 3, 20500, Turku (Finland); Ihalainen, Petri, E-mail: petri.ihalainen@abo.fi [Laboratory of Physical Chemistry, Faculty of Science and Engineering, Center for Functional Materials, Åbo Akademi University, Porthaninkatu 3, 20500, Turku (Finland); Törngren, Björn, E-mail: bjorn.torngren@abo.fi [Laboratory of Physical Chemistry, Faculty of Science and Engineering, Center for Functional Materials, Åbo Akademi University, Porthaninkatu 3, 20500, Turku (Finland); Rosqvist, Emil, E-mail: emil.rosqvist@abo.fi [Laboratory of Physical Chemistry, Faculty of Science and Engineering, Center for Functional Materials, Åbo Akademi University, Porthaninkatu 3, 20500, Turku (Finland); Pesonen, Markus, E-mail: markus.pesonen@abo.fi [Physics, Faculty of Science and Engineering, Center for Functional Materials, Åbo Akademi University, Porthaninkatu 3, 20500, Turku (Finland); Peltonen, Jouko, E-mail: jouko.peltonen@abo.fi [Laboratory of Physical Chemistry, Faculty of Science and Engineering, Center for Functional Materials, Åbo Akademi University, Porthaninkatu 3, 20500, Turku (Finland)

2016-02-28

Graphical abstract: - Highlights: • Transparent self-supported latex films were fabricated by a peel-off process. • Various template substrates were used for creating e.g. hierarchically structured latex films. • Ultra-thin and semi-transparent conductive gold electrodes were evaporated on the latex films.Electrochemical experiments were carried out to verify the applicability of the electrodes. - Abstract: Different length scale alterations in topography, surface texture, and symmetry are known to evoke diverse cell behavior, including adhesion, orientation, motility, cytoskeletal condensation, and modulation of intracellular signaling pathways. In this work, self-supported latex films with well-defined isotropic/anisotropic surface features and hierarchical morphologies were fabricated by a peel-off process from different template surfaces. In addition, the latex films were used as substrates for evaporated ultrathin gold films with nominal thicknesses of 10 and 20 nm. Optical properties and topography of the samples were characterized using UV–vis spectroscopy and Atomic Force Microscopy (AFM) measurements, respectively. The latex films showed high-level transmittance of visible light, enabling the fabrication of semi-transparent gold electrodes. Electrochemical impedance spectroscopy (EIS) measurements were carried out for a number of days to investigate the long-term stability of the electrodes. The effect of 1-octadecanethiol (ODT) and HS(CH{sub 2}){sub 11}OH (MuOH) thiolation and protein (human serum albumin, HSA) adsorption on the impedance and capacitance was studied. In addition, cyclic voltammetry (CV) measurements were carried out to determine active medicinal components, i.e., caffeic acid with interesting biological activities and poorly water-soluble anti-inflammatory drug, piroxicam. The results show that the fabrication procedure presented in this study enables the formation of platforms with hierarchical morphologies for multimodal

Characterization and modulation of canine mast cell derived eicosanoids

Science.gov (United States)

Lin, Tzu-Yin; London, Cheryl A.

2013-01-01

Mast cells play an important role in both innate and acquired immunity as well as several pathological conditions including allergy, arthritis and neoplasia. They influence these processes by producing a variety of mediators including cytokines, chemokines and eicosanoids. Very little is currently known about the spectrum of inflammatory mediators, particularly eicosanoids (prostaglandins and leukotrienes), produced by canine mast cells. This is important since modulating mast cell derived eicosanoids may help in the treatment of autoimmune and inflammatory disorders. The purpose of this study was to investigate the spectrum of eicosanoids produced by normal canine mast cells and to evaluate the effects of cytokines and non-steroidal anti-inflammatory mediators (NSAIDS) on eicosanoid production and release. Canine bone marrow derived cultured mast cells (cBMCMCs) expressed COX-1, COX-2, and 5-LOX and synthesized and released PGD2, PGE2, LTB4, and LTC4 following activation by a variety of stimuli. The selective COX-2 NSAIDs carprofen (Rimadyl®) and deracoxib (Deramaxx®) inhibited PGD2 and PGE2 production but only slightly inhibited LTB4 and LTC4. The mixed COX-1/COX-2 inhibitor piroxicam blocked PGD2 and PGE2 production, but upregulated LTC4 following treatment while tepoxilan (Zubrin®), a pan COX/LOX inhibitor, markedly reduced the production of all eicosanoids. The LOX inhibitor nordihydroguaiaretic acid (NDGA) prevented LTB4/LTC4 release and BMBMC degranulation. Pre-incubation of cBMCMCs with IL-4 and SCF sensitized these cells to degranulation in response to substance P. In conclusion, canine BMCMCs produce an array of eicosanoids similar to those produced by mast cells from other species. Tepoxilan appeared to be the most effective NSAID for blocking eicosanoid production and thus may be useful for modulating mast cell mediated responses in dogs. PMID:20036014

Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes

International Nuclear Information System (INIS)

Nadanaciva, Sashi; Aleo, Michael D.; Strock, Christopher J.; Stedman, Donald B.; Wang, Huijun; Will, Yvonne

2013-01-01

To reduce costly late-stage compound attrition, there has been an increased focus on assessing compounds in in vitro assays that predict attributes of human safety liabilities, before preclinical in vivo studies are done. Relevant questions when choosing a panel of assays for predicting toxicity are (a) whether there is general concordance in the data among the assays, and (b) whether, in a retrospective analysis, the rank order of toxicity of compounds in the assays correlates with the known safety profile of the drugs in humans. The aim of our study was to answer these questions using nonsteroidal anti-inflammatory drugs (NSAIDs) as a test set since NSAIDs are generally associated with gastrointestinal injury, hepatotoxicity, and/or cardiovascular risk, with mitochondrial impairment and endoplasmic reticulum stress being possible contributing factors. Eleven NSAIDs, flufenamic acid, tolfenamic acid, mefenamic acid, diclofenac, meloxicam, sudoxicam, piroxicam, diflunisal, acetylsalicylic acid, nimesulide, and sulindac (and its two metabolites, sulindac sulfide and sulindac sulfone), were tested for their effects on (a) the respiration of rat liver mitochondria, (b) a panel of mechanistic endpoints in rat hepatocytes, and (c) the viability and organ morphology of zebrafish. We show good concordance for distinguishing among/between NSAID chemical classes in the observations among the three approaches. Furthermore, the assays were complementary and able to correctly identify “toxic” and “non-toxic” drugs in accordance with their human safety profile, with emphasis on hepatic and gastrointestinal safety. We recommend implementing our multi-assay approach in the drug discovery process to reduce compound attrition. - Highlights: • NSAIDS cause liver and GI toxicity. • Mitochondrial uncoupling contributes to NSAID liver toxicity. • ER stress is a mechanism that contributes to liver toxicity. • Zebrafish and cell based assays are complimentary

Cost-effectiveness analysis for joint pain treatment in patients with osteoarthritis treated at the Instituto Mexicano del Seguro Social (IMSS: Comparison of nonsteroidal anti-inflammatory drugs (NSAIDs vs. cyclooxygenase-2 selective inhibitors

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Mejía-Aranguré Juan

2008-11-01

Full Text Available Abstract Background Osteoarthritis (OA is one of the main causes of disability worldwide, especially in persons >55 years of age. Currently, controversy remains about the best therapeutic alternative for this disease when evaluated from a cost-effectiveness viewpoint. For Social Security Institutions in developing countries, it is very important to assess what drugs may decrease the subsequent use of medical care resources, considering their adverse events that are known to have a significant increase in medical care costs of patients with OA. Three treatment alternatives were compared: celecoxib (200 mg twice daily, non-selective NSAIDs (naproxen, 500 mg twice daily; diclofenac, 100 mg twice daily; and piroxicam, 20 mg/day and acetaminophen, 1000 mg twice daily. The aim of this study was to identify the most cost-effective first-choice pharmacological treatment for the control of joint pain secondary to OA in patients treated at the Instituto Mexicano del Seguro Social (IMSS. Methods A cost-effectiveness assessment was carried out. A systematic review of the literature was performed to obtain transition probabilities. In order to evaluate analysis robustness, one-way and probabilistic sensitivity analyses were conducted. Estimations were done for a 6-month period. Results Treatment demonstrating the best cost-effectiveness results [lowest cost-effectiveness ratio $17.5 pesos/patient ($1.75 USD] was celecoxib. According to the one-way sensitivity analysis, celecoxib would need to markedly decrease its effectiveness in order for it to not be the optimal treatment option. In the probabilistic analysis, both in the construction of the acceptability curves and in the estimation of net economic benefits, the most cost-effective option was celecoxib. Conclusion From a Mexican institutional perspective and probably in other Social Security Institutions in similar developing countries, the most cost-effective option for treatment of knee and/or hip OA

Efeito do meloxicam sobre a lesão de isquemia e reperfusão em músculo esquelético de ratos Effect of meloxicam on ischemia-reperfusion injury in skeletal muscle of rats

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Vitor A. Uhle

2000-01-01

Full Text Available Os antiinflamatórios não esteroidais, derivados do piroxicam, agem como varredores de radicais livres de oxigênio em experimentos in vitro. O objetivo deste trabalho foi analisar o efeito do meloxicam em músculos esqueléticos de ratos submetidos à isquemia e reperfusão com base na análise de liberação de malondialdeído da membrana celular ( indicador de peroxidação lipídica provocada pelos radicais livres. Dezoito ratos Wistar foram divididos em 2 grupos de 9. O grupo I (grupo sham foi tratado previamente com 3g/kg de peso de solução fisiológica e o grupo II com 3g/kg de peso de meloxicam por via peritoneal. Após 5 min os ratos foram submetidos a 3h de isquemia total ( torniquete e 45 min de reperfusão das patas posteriores esquerdas. Colheram-se biópsias dos músculos isquêmicos e reperfundidos e das patas controles (contralaterais para a dosagem de malondialdeído. A análise das diferenças de concentração do malondiadeído nas patas controles e reperfundidas no grupo I (43,7± 60,7; n=9 em relação ao grupo II (21,7± 49,5; n=9 não mostrou alteração significante (p=0,3. Os dados obtidos, neste trabalho, mostram que o meloxicam não protege a musculatura esquelética dos danos causados pela isquemia e reperfusão, com base na análise do malondialdeído tissular após 3h de isquemia e 45 min de reperfusão.

Cuantificación de glibenclamida en muestras de limpieza de equipos farmacéuticos mediante cromatografía líquida de alta resolución

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Alen Nils Baeza Fonte

2012-03-01

Full Text Available Objetivo: proponer un procedimiento analítico selectivo para la cuantificación de glibenclamida en muestras de limpieza de equipos farmacéuticos mediante cromatografía líquida de alta resolución. Métodos: la fase móvil consistió en una mezcla equivalente de volúmenes de acetonitrilo y solución amortiguadora KH2PO4 de concentración 0,037 mol/L a pH 5,25 y flujo 1,5 mL/min, en una columna Nucleosil 100 C8. La glibenclamida se inyectó con progesterona como estándar interno y empleando detector UV a una l= 230 nm. Resultados: el método resultó lineal en el intervalo de concentraciones de 0,4-150 mg/mL, teniendo como límites de detección y cuantificación 10 y 40 ng/mL respectivamente y siendo específico al analito en presencia del placebo, sus productos de degradación y a otros ingredientes farmacéuticamente activos. Se consideraron potenciales de interferencias para el método propuesto: captopril, clortalidona, dexametasona, digoxina, 8-cloroteofilina, difenhidramina HCl, fenobarbital, haloperidol, hidroclorotiazida, ácido fumárico, ketotifeno, metoclopramida HCl, piridoxina HCl, piroxicam, prednisona y nifedipino. Se identificaron: ibuprofeno, indometacina, trifluoperazina HCl, tioridazina HCl e imipramina HCl, como interferentes del procedimiento en concentraciones cercanas a 10 mg/mL. Conclusiones: el método desarrollado es sensible, rápido y especialmente selectivo para la evaluación de residuales del principio activo glibenclamida en equipos de producción de tabletas, empleando un muestreo por hisopado, y pudiera utilizarse potencialmente cuando exista sospecha de contaminación cruzada de glibenclamida con otros fármacos de los aquí descritos.

Anti-inflammatory drugs suppress proliferation and induce apoptosis through altering expressions of cell cycle regulators and pro-apoptotic factors in cultured human osteoblasts

International Nuclear Information System (INIS)

Chang, J.-K.; Li, C.-J.; Liao, H.-J.; Wang, C.-K.; Wang, G.-J.; Ho, M.-L.

2009-01-01

It has been reported that anti-inflammatory drugs (AIDs) inhibited bone repair in animal studies, and suppressed proliferation and induced cell death in rat osteoblast cultures. In this study, we further investigated the molecular mechanisms of AID effects on proliferation and cell death in human osteoblasts (hOBs). We examined the effects of dexamethasone (10 -7 and 10 -6 M), non-selective non-steroidal anti-inflammatory drugs (NSAIDs): indomethacin, ketorolac, piroxicam and diclofenac (10 -5 and 10 -4 M), and COX-2 inhibitor: celecoxib (10 -6 and 10 -5 M) on proliferation, cytotoxicity, cell death, and mRNA and protein levels of cell cycle and apoptosis-related regulators in hOBs. All the tested AIDs significantly inhibited proliferation and arrested cell cycle at G0/G1 phase in hOBs. Celecoxib and dexamethasone, but not non-selective NSAIDs, were found to have cytotoxic effects on hOB, and further demonstrated to induce apoptosis and necrosis (at higher concentration) in hOBs. We further found that indomethacin, celecoxib and dexamethasone increased the mRNA and protein expressions of p27 kip1 and decreased those of cyclin D2 and p-cdk2 in hOBs. Bak expression was increased by celecoxib and dexamethasone, while Bcl-XL level was declined only by dexamethasone. Furthermore, the replenishment of PGE1, PGE2 or PGF2α did not reverse the effects of AIDs on proliferation and expressions of p27 kip1 and cyclin D2 in hOBs. We conclude that the changes in expressions of regulators of cell cycle (p27 kip1 and cyclin D2) and/or apoptosis (Bak and Bcl-XL) by AIDs may contribute to AIDs caused proliferation suppression and apoptosis in hOBs. This effect might not relate to the blockage of prostaglandin synthesis by AIDs

PAMPA--a drug absorption in vitro model. 5. Unstirred water layer in iso-pH mapping assays and pKa(flux)--optimized design (pOD-PAMPA).

Science.gov (United States)

Ruell, Jeffrey A; Tsinman, Konstantin L; Avdeef, Alex

2003-12-01

Iso-pH mapping unstirred parallel artificial membrane permeability assay (PAMPA) was used to measure the effective permeability, P(e), as a function of pH from 3 to 10, of five weak monoprotic acids (ibuprofen, naproxen, ketoprofen, salicylic acid, benzoic acid), an ampholyte (piroxicam), five monoprotic weak bases (imipramine, verapamil, propranolol, phenazopyridine, metoprolol), and a diprotic weak base (quinine). The intrinsic permeability, P(o), the unstirred water layer (UWL) permeability, P(u), and the apparent pK(a) (pK(a)(flux)) were determined from the pH dependence of logP(e). The underlying permeability-pH equations were derived for multiprotic weak acids, weak bases and ampholytes. The average thickness of the unstirred water layer on each side of the membrane was estimated to be nearly 2000 microm, somewhat larger than that found in Caco-2 permeability assays (unstirred). Since the UWL thickness in the human intestine is believed to be about forty times smaller, it is critical to correct the in vitro permeability data for the effect of the UWL. Without such correction, the in vitro permeability coefficient of lipophilic molecules would be indicative only of the property of water. In single-pH PAMPA (e.g. pH 7.4), the uncertainty of the UWL contribution can be minimized if a specially-selected pH (possibly different from 7.4) were used in the assay. From the analysis of the shapes of the log P(e)-pH plots, a method to improve the selection of the assay pH, called pK(a)(flux)-optimized design (pOD-PAMPA), was described and tested. From an optimally-selected assay pH, it is possible to estimate P(o), as well as the entire membrane permeability-pH profile.

Margem de segurança do meloxicam em cães: efeitos deletérios nas células sangüíneas e trato gastrintestinal Margin of safety of meloxicam in dogs: deleterious effects on blood cells and gastrointestinal tract

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Marilac Maria Arnaldo Alencar

2003-06-01

Full Text Available Este trabalho investigou a margem de segurança do inibidor COX-2, meloxicam, em cães, enfocando seus efeitos deletérios nas células sangüíneas e no trato gastrintestinal. Para tanto, após uma avaliação clínico-laboratorial, os cães foram distribuídos nos seguintes grupos: I (placebo; n= 3, II (piroxicam; 1,0mg kg-1; n= 5, III (meloxicam; 0,2mg kg-1; n= 5, IV (meloxicam;1,0mg kg-1; n= 5 e V (meloxicam; 2,0mg kg-1; n= 5. Os fármacos foram usados, por via oral, por 16 dias. No 17º dia, repetiu-se o hemograma completo e, então, procedeu-se a eutanásia seguida pela necrópsia. No grupo I, não houve alterações dignas de nota. No grupo II, todos os cães apresentaram episódios moderados de vômito e diarréia. O perfil celular sangüíneo não foi significativamente modificado. Em dois cães, houve redução no hematócrito e na hemoglobina. Na necropsia, observaram-se focos hemorrágicos e lesões gastriduodenais moderadas. A análise microscópica revelou a presença de gastrite e enterite ulcerativa. No grupo III, quatro cães (80% apresentaram vômito e diarréia, sem alteração no perfil celular sangüíneo. Na análise macroscópica, observaram-se lesões brandas na mucosa gástrica e focos hemorrágicos no duodeno em quatro cães. Na histopatologia, observaram-se lesões sugestivas de discreta gastroenterite. No grupo IV, os cinco cães tiveram vômito e diarréia sanguinolenta. Quatro deles (80% apresentaram anemia (p This study investigated the margin of safety of the COX-2e inhibitor, meloxicam on blood cells and gastrointestinal tract of dogs. After a clinical and laboratorial examination, the dogs were distributed in the following groups: I (placebo; n=3, II (piroxicam: 1.0mg kg-1; n=5, III (meloxicam: 0.2mg kg-1; n=5, IV (meloxican: 1.0mg kg-1; n=5 and V (meloxican: 2.0mg kg-1; n=5. The drugs were given orally for 16 days. On the 17th day the complete hemogram was repeated and the euthanasia and necropsy were then

Effects of non-steroidal anti-inflammatory drugs on cell proliferation and death in cultured epiphyseal-articular chondrocytes of fetal rats

International Nuclear Information System (INIS)

Chang, J.-K.; Wu, S.-C.; Wang, G.-J.

2006-01-01

Previous reports indicated that non-steroidal anti-inflammatory drugs (NSAIDs) suppress bone repair. Our previous study further found that ketorolac delayed the endochondral bone formation, and the critical effective timing was at the early stage of repair. Furthermore, we found that NSAIDs suppressed proliferation and induced cell death of cultured osteoblasts. In this study, we hypothesized that chondrocytic proliferation and death, which plays an important role at the early stage of endochondral bone formation, might be affected by NSAIDs. Non-selective NSAIDs, indomethacin, ketorolac, diclofenac and piroxicam; cyclooxygenase-2 (COX-2) selective NSAIDs, celecoxib and DFU (an analog of rofecoxib); prostaglandins (PGs), PGE1, PGE2 and PGF2α; and each NSAID plus each PG were tested. The effects of NSAIDs on proliferation, cell cycle kinetics, cytotoxicity and cell death of epiphyseal-articular chondrocytes of fetal rats were examined. The results showed that all the tested NSAIDs, except DFU, inhibited thymidine incorporation of chondrocytes at a concentration range (10 -8 to 10 -4 M) covering the theoretic therapeutic concentrations. Cell cycle was arrested by NSAIDs at the G /G 1 phase. Upon a 24 h treatment, LDH leakage and cell death (both apoptosis and necrosis) were significantly induced by the four non-selective NSAIDs in chondrocyte cultures. However, COX-2 inhibitors revealed non-significant effects on cytotoxicity of chondrocytes except higher concentration of celecoxib (10 -4 M). Replenishments of PGE1, PGE2 or PGF2α could not reverse the effects of NSAIDs on chondrocytic proliferation and cytotoxicity. In this study, we found that therapeutic concentrations of non-selective NSAIDs caused proliferation suppression and cell death of chondrocytes, suggesting these adverse effects may be one of the reasons that NSAIDs delay the endochondral ossification during bone repair found in previous studies. Furthermore, these effects of NSAIDs may act via PG

Profile of diseases prevalent in a tribal locality in Jharkhand, India: A family medicine practitioner′s perspective

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Sumit Kumar

2015-01-01

Full Text Available Background: Majority of Indian population is dependent on general practitioners (GPs for medical services at primary care level in India. They are most preferred and considered to be first contact person for medical services at primary care level. But advances in medical science has put more emphasis on specialist culture and average Bachelor of Medicine and Bachelor of Surgery (MBBS graduates who are working as general physician are gradually feeling themselves less competent because they are less exposed to latest advances in treatment of diseases. Amidst such scenario, Christian Medical College (CMC has come up with an idea: "The refer less and resolve more initiative". It has started a decentralized 2-year family medicine distance diploma course (Postgraduate Diploma in Family Medicine (PGDFM now accredited by Dr. MGR Medical University, Chennai, Tamil Nadu, that trains the GPs to become family medicine specialist. Materials and Methods: As component of PGDFM course, this study was conducted to provide better understanding of prevalent ailments and common treatment provided by the GPs in the community at present giving key insight of current practice in rural area by a registered family medicine practitioner. Results: As part of study, among 500 patients evaluated, three most common diagnosis were upper respiratory infections (URIs; 18%, acute gastroenteritis including water-borne diseases (15.8%, and anemia (10.4%. Treatment given to these patients comprised of mostly of antipyretic, analgesic, and antimicrobial agents. Most common drug prescribed was paracetamol for fever. Other common drugs prescribed were amoxicillin/clavulanic acid, chloroquine, artemisin derivative, doxycycline, co-trimoxazole, miltefosine, cephalexin, ceftriaxone sodium, cefixime, oral rehydration salts, ranitidine, omeprazole, pantoprazole, metronidazole, albendazole, ondansetron, diclofenac sodium, piroxicam, ibuprofen, diphenhydramine, codeine-sulfate, amlodipine

Analysis of an Adulterated Herbal Medicinal Product Using Ultra-Performance Liquid Chromatography Coupled with QTOF Mass Spectrometry

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Kate Yu

2016-11-01

Full Text Available The reports of severe adverse effects and fatalities associated with herbal medicinal products adulterated with synthetic compounds have raised global concerns. The objective of this study is to analyze one commercial herbal medicinal product suspected to be adulterated with synthetic drugs in order to identify potential adulterants, to verify if the product contained the herbs listed as ingredients in label claim and to determine quality consistency among different batches of the product. Analyses of suspected product obtained from seven different batches were performed using ultra performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS with multiple data processing tools and multivariate analyses. In addition, 23 individual powdered herbs (12 as per label claim and 11 suspected herbs, 11 marker compounds of the labeled herbs and five suspected synthetic drugs as adulterants were also concurrently analyzed to have clear understanding of product composition. Based on our analysis, the major ingredients of studied product were found to be 5 synthetic compounds: caffeine, chlorphenamine, piroxicam, betamethasone and oxethazaine. Three of them have been found to exceed their recommended doses. From the herbal composition analysis, GanCao (Glycyrrhizae radix et rhizoma was found to be the main ingredient, which is not among the claimed 12 herbs that were supposed to be in the product. Other herbs detected as minor ingredients were MuGua (Chaenomelis fructus, DangGui (Angelicae sinensis radix, and HuangQi (Astragali radix, which are among the 12 herbs that were supposed to be in the product. Based on our results we demonstrated that UPLC-QTOF MS is an effective and versatile tool for the analysis of herbal medicinal products. It is highly desirable to have a streamlined process with automatic workflow and fit-for-purpose database to increase efficiency and productivity of sample analysis. Results of

Correlation between drug–drug interaction-induced Stevens–Johnson syndrome and related deaths in Taiwan

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Fu-Jen Cheng

2016-04-01

Full Text Available Concomitant use of some drugs can lead to interactions between them resulting in severe adverse effects. To date, there are few reports of incidences of Stevens-Johnson syndrome (SJS associated with combination drug administration. Therefore, we studied the relationship between drug combinations and SJS-related mortality, with the hope that a retrospective study of this nature would provide information crucial for the prevention of future drug-drug interaction related deaths attributable to SJS. This retrospective longitudinal study used mortality cases from 1999 to 2008 that were diagnosed as erythema multiforme (International Classification of Diseases, Ninth Revision, Clinical Modification 695.1 from the National Health Insurance database in Taiwan. Statistical comparisons of the results were performed using analysis of variance (ANOVA, independent sample t-tests, and odds ratio (OR. In this way, the relationship between combinations of SJS-inducing drugs and mortality could be determined. A total of 111 patients who had died, including 63 males and 48 females (66.0 ± 20 and 70.0 ± 17.7 years, respectively, were suspected of having experienced drug-drug interaction-related adverse effects. The associated drug combinations included allopurinol and ampicillin (p = 0.049, carbamazepine and sulfamethoxazole/trimethoprim (TMP (p < 0.0001, carbamazepine and phenytoin (p < 0.0001, sulfamethoxazole/TMP and phenytoin (p = 0.015, sulfadoxine and piroxicam (p = 0.045, phenobarbital and cephalexin (p < 0.0001, ampicillin and erythromycin (p < 0.0001, erythromycin and minocycline (p < 0.0001, and vancomycin and ethambutol (p < 0.0001 administered 1 month before the patients' deaths. Caution should be exercised when administering any drugs that may possibly induce SJS. In addition, attention should be paid to ensure prompt identification of possible drug-drug interactions, and patients should be closely monitored. Furthermore

Effect of oral premedication on the anaesthetic efficacy of inferior alveolar nerve block in patients with irreversible pulpitis - A systematic review and network meta-analysis of randomized controlled trials.

Science.gov (United States)

Pulikkotil, S J; Nagendrababu, V; Veettil, S K; Jinatongthai, P; Setzer, F C

2018-02-26

This systematic review (SR; PROSPERO database: CRD42017075160) and network meta-analysis (NMA) identified the most effective oral premedication for anaesthetic success of inferior alveolar nerve blocks (IANB) in cases of irreversible pulpitis. Medline and Ebscohost databases were searched up until 10/2017. Randomized controlled trials (RCT) studying the effect of oral premedication, alone or in combination, on the success of IANB for cases of irreversible pulpitis, compared to placebo or other oral premedications, were included. Quality of the included studies was appraised by the revised Cochrane risk of bias tool for randomized trials. Pairwise analysis, NMA and quality of evidence assessment using GRADE criteria were performed. Nineteen studies (n = 1654 participants) were included. NMA demonstrated that compared to placebo, dexamethasone was most effective in increasing anaesthetic success (RR, 2.92 [95% CI 1.74,4.91]; SUCRA = 0.96), followed by NSAIDs (RR, 1.92 [95% CI 1.63,2.27], SUCRA = 0.738) and Tramadol (RR, 2.03 [95% CI 1.18,3.49], SUCRA = 0.737). Premedication with acetaminophen added to NSAIDs demonstrated similar efficacy as NSAIDs alone (RR, 1.06 [95% CI 0.79,1.43]). Sensitivity analyses proved the superiority of dexamethasone or NSAIDs over any other premedications. Subgroup analyses of specific dosages in comparison with placebo demonstrated that dexamethasone 0.5 mg was most effective, followed by ketorolac 10 mg, piroxicam 20 mg, ibuprofen 400 mg + acetaminophen 500 mg and Tramadol 50 mg. Ibuprofen 400 mg, 600 mg and 800 mg had a significantly improved IANB success, while Ibuprofen 300 mg had no effect. Oral premedication with dexamethasone, NSAIDs or Tramadol significantly increased anaesthetic success. More trials are needed to evaluate the premedication effects of dexamethasone or Tramadol for improved anaesthetic success of IANB when treating irreversible pulpitis. © 2018 International Endodontic Journal. Published by John

Retrospective Study of Reported Adverse Events Due to Complementary Health Products in Singapore From 2010 to 2016

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Yimin Xu

2018-06-01

Full Text Available The objective of this study is to collate and analyse adverse event reports associated with the use of complementary health products (CHP submitted to the Health Sciences Authority (HSA of Singapore for the period 2010–2016 to identify various trends and signals for pharmacovigilance purposes. A total of 147,215 adverse event reports suspected to be associated with pharmaceutical products and CHP were received by HSA between 2010 and 2016. Of these, 143,191 (97.3% were associated with chemical drugs, 1,807 (1.2% with vaccines, 1,324 (0.9% with biological drugs (biologics, and 893 (0.6% with CHP. The number of adverse event reports associated with Chinese Proprietary Medicine, other complementary medicine and health supplements are presented. Eight hundred and ninety three adverse event reports associated with CHP in the 7-year period have been successfully collated and analyzed. In agreement with other studies, adverse events related to the “skin and appendages disorders” were the most commonly reported. Most of the cases involved dermal allergies (e.g., rashes associated with the use of glucosamine products and most of the adulterated products were associated with the illegal addition of undeclared drugs for pain relief. Dexamethasone, chlorpheniramine, and piroxicam were the most common adulterants detected. Reporting suspected adverse events is strongly encouraged even if the causality is not confirmed because any signs of clustering will allow rapid regulatory actions to be taken. The findings from this study help to create greater awareness on the health risks, albeit low, when consuming CHP and dispelling the common misconception that “natural” means “safe.” In particular, healthcare professionals and the general public should be aware of potential adulteration of CHP. The analysis of spontaneously reported adverse events is an important surveillance system in monitoring the safety of CHP and helps in the understanding of the

Non-steroidal anti-inflammatory drugs and gastroprotection with proton pump inhibitors: a focus on ketoprofen/omeprazole.

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Gigante, Antonio; Tagarro, Ignacio

2012-04-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed agents for rheumatic disorders such as osteoarthritis (OA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Despite the known association between NSAID use and gastropathy, however, only around one-third of patients at risk of NSAID-induced gastrointestinal toxicity receive adequate gastroprotection, and as many as 44% of these patients are non-adherent. We review the co-prescription of proton pump inhibitors (PPIs) for the prevention of NSAID-induced gastropathy, with a particular focus on the first fixed-dose NSAID/PPI formulation: ketoprofen/omeprazole modified-release capsules. The ketoprofen/omeprazole fixed-dose combination is available in doses of 100 mg/20 mg, 150 mg/20 mg or 200 mg/20 mg as a single capsule for once-daily administration. Ketoprofen monotherapy has been shown to be generally equivalent to other NSAIDs when used in the treatment of OA. In RA, ketoprofen has demonstrated equivalent efficacy to diclofenac, indometacin, piroxicam, aceclofenac, phenylbutazone, naproxen and flurbiprofen. Studies comparing ketoprofen with ibuprofen and sulindac in patients with RA have, in general, favoured ketoprofen. Studies in AS have generally reported similar efficacy between ketoprofen and phenylbutazone and pirprofen. Prophylaxis with omeprazole is effective for the prevention of gastroduodenal ulcers, maintenance of remission and alleviation of dyspeptic symptoms in NSAID recipients. Omeprazole is well tolerated, and adverse events are generally gastrointestinal in nature. The fixed-dose combination of ketoprofen and omeprazole has demonstrated bioequivalence to the respective monotherapies. The incidence of digestive symptoms and the need for dose reduction was reported to be lower with the combination than with its components. Ketoprofen/omeprazole modified-release capsules are the first fixed-dose NSAID/PPI formulation to be approved. This formulation

Structural damage and changes in eicosanoid metabolites in the gastric mucosa of rats and pigs induced by anti-inflammatory drugs of varying ulcerogenicity.

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Rainsford, K D

1986-01-01

The object of the studies reviewed here has been to correlate the time-course of ultrastructural changes induced by oral administration of a range of non-steroidal anti-inflammatory (NSAI) drugs with effects on eicosanoid metabolism and drug absorption, so as to discriminate what biochemical/cellular and pharmacological factors account for their varying ulcerogenicity. Oral administration of highly ulcerogenic drugs (e.g. aspirin, diclofenac, indomethacin, piroxicam) to rats causes rapid damage to surface and gastric mucous cells, selective parietal cell damage, and extensive disruption of endothelial cells of submucosal microcapillaries (especially with aspirin) with accompanying extravasation of blood cell components. These changes are coincident with depressed levels of PGE2/6-keto-PGF1 alpha (measured by GC/MS or RIA) and uptake of the drugs (measured by scintillation counting or HPLC). Low ulcerogenic NSAI drugs (e.g. azapropazone, benoxaprofen and fenclofenac) causes very little damage to the surface mucosal cells. Azapropazone has been found to be well absorbed, and benoxaprofen and fenclofenac somewhat more slowly, so for the latter two drugs their low rate of absorption might also be a factor in their reduced ulcerogenicity. Aspirin, azapropazone and benoxaprofen have been shown to reduce 5-HETE levels (RIA), although the latter two drugs were more effective than aspirin. Thus, they result in the inhibition of PG production, by cyclo-oxygenase inhibition (with potential adverse effects from excess oxyradical and/or production of HETE's) with inhibition of the lipoxygenase pathway. The time-sequence of changes induced by single oral doses of indomethacin or other NSAI drugs on the ultrastructure and the prostanoid metabolism of the pig gastric mucosa parallelled those seen in the rat. Attempts to determine whether co-administration of NSAI drugs might reduce the inhibition of PG cyclo-oxygenase by more potent inhibitors (e.g. indomethacin) have been

Antihyperalgesic Properties of Honokiol in Inflammatory Pain Models by Targeting of NF-κB and Nrf2 Signaling

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Sidra Khalid

2018-03-01

Full Text Available The present study investigates the possible anti-nociceptive effect of intraperitoneal (i.p. honokiol: a phenolic compound originally isolated from Magnolia officinalis, in acute and chronic inflammatory pain models. Doses of 0.1, 5, and 10 mg/kg honokiol were administered in carrageenan induced pain and the dose (honokiol 10 mg/kg i.p. with most significant response among behavioral tests was selected for further experiments. The i.p. administration of honokiol inhibits mechanical hyperalgesia, mechanical allodynia, and thermal hyperalgesia, without causing any apparent toxicity. To elucidate the effect of honokiol on various cytokines and antioxidant enzymes, quantitative real-time-PCR was performed to determine the expression levels of pro-inflammatory cytokines and antioxidant enzymes. It is demonstrated that honokiol significantly reduced the expression levels of tumor necrosis factor (TNF-α, interleukin-1β (IL-1β, interleukin-6 (IL-6, and vascular endothelial growth factor (VEGF. Similarly, honokiol was also found to potentiate the expression of nuclear factor erythroid 2–related factor 2 (Nrf2, superoxide dismutase 2 (SOD2, and heme oxygenase-1 (HO-1 levels. Additionally, honokiol significantly reduced plasma nitrite levels as compared to complete Freund’s adjuvant (CFA induced group. X-ray analysis and hematoxylin and eosin (H&E staining of inflamed and treated paws showed that honokiol reduced the inflammation with significantly less leukocyte infiltration and soft tissue inflammation. In order to explore the possible mechanism of action of honokiol, agonists [piroxicam (5 mg/kg, tramadol (50 mg/kg, and gabapentin (5 mg/kg i.p.] as well as antagonists [naloxone (4 mg/kg, olanzapine (10 mg/kg, and flumazenil (0.2 mg/kg i.p.] were used to study involvement of various receptors on the anti-nociceptive effect of honokiol. The potential side effects of honokiol on muscle activity were assessed. An adverse effect testing of honokiol by

Treatment of experimental colitis in mice with LMP-420, an inhibitor of TNF transcription

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Cianciolo George

2008-03-01

Full Text Available Abstract Background LMP-420 is a boronic acid-containing purine nucleoside analogue that transcriptionally inhibits TNF production but is non-cytotoxic to TNF-producing cells. Methods This study investigated the efficacy of LMP-420 as an anti-inflammatory agent in acute and chronic colitis induced by oral administration of dextran sulfate sodium (DSS to mice and in chronic colitis following piroxicam administration to IL-10-deficient mice. The severity of colon inflammation was assessed histologically. TNF levels were measured by enzyme immunoassay. Results Administration of DSS for 7 days resulted in severe acute colitis that was associated with a marked increase in stool and colon tissue TNF levels. Initiation of therapy with intraperitoneal (i.p. LMP-420 on day 4 of DSS exposure decreased colonic TNF to near normal levels on day 7. However, neither i.p. nor oral treatment with LMP-420 affected the development or severity of acute DSS colitis. Initiation of LMP-420 therapy after 3 cycles of DSS administration to establish chronic colitis also had no effect on the severity of chronic colitis. Analysis of colonic TNF combined with longitudinal analysis of TNF and TNF receptor (TNF-RII levels in stool during the development of chronic DSS colitis demonstrated that the initially elevated colonic TNF levels returned to normal despite intense on-going inflammation in mice with chronic colitis. RAG-2-/- mice deficient in T and B cells also developed severe ongoing colitis in response to 3 cycles of DSS, but showed marked differences vs. wild type mice in stool TNF and TNF-RII in response to DSS exposure. Systemic and oral LMP-420 treatment for 16 days decreased colonic TNF levels in IL-10-deficient mice with chronic colitis, with a trend to decreased histologic inflammation for oral LMP-420. Conclusion These studies demonstrate that short-term treatment with a transcriptional inhibitor of TNF production can decrease systemic and local colonic levels

FCERI AND HISTAMINE METABOLISM GENE VARIABILITY IN SELECTIVE RESPONDERS TO NSAIDS

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Gemma Amo

2016-09-01

Full Text Available The high-affinity IgE receptor (Fcε RI is a heterotetramer of three subunits: Fcε RIα, Fcε RIβ and Fcε RIγ (αβγ2 encoded by three genes designated as FCER1A, FCER1B (MS4A2 and FCER1G, respectively. Recent evidence points to FCERI gene variability as a relevant factor in the risk of developing allergic diseases. Because Fcε RI plays a key role in the events downstream of the triggering factors in immunological response, we hypothesized that FCERI gene variants might be related with the risk of, or with the clinical response to, selective (IgE mediated non-steroidal anti-inflammatory (NSAID hypersensitivity.From a cohort of 314 patients suffering from selective hypersensitivity to metamizole, ibuprofen, diclofenac, paracetamol, acetylsalicylic acid (ASA, propifenazone, naproxen, ketoprofen, dexketoprofen, etofenamate, aceclofenac, etoricoxib, dexibuprofen, indomethacin, oxyphenylbutazone or piroxicam, and 585 unrelated healthy controls that tolerated these NSAIDs, we analyzed the putative effects of the FCERI SNPs FCER1A rs2494262, rs2427837 and rs2251746; FCER1B rs1441586, rs569108 and rs512555; FCER1G rs11587213, rs2070901 and rs11421. Furthermore, in order to identify additional genetic markers which might be associated with the risk of developing selective NSAID hypersensitivity, or which may modify the putative association of FCERI gene variations with risk, we analyzed polymorphisms known to affect histamine synthesis or metabolism, such as rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and DAO genes.No major genetic associations with risk or with clinical presentation, and no gene-gene interactions, or gene-phenotype interactions (including age, gender, IgE concentration, antecedents of atopy, culprit drug or clinical presentation were identified in patients. However, logistic regression analyses indicated that the presence of antecedents of atopy and the DAO SNP rs2052129 (GG

Malignant melanoma in 63 dogs (2001-2011): the effect of carboplatin chemotherapy on survival.

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Brockley, L K; Cooper, M A; Bennett, P F

2013-01-01

.0002 and p=0.009, respectively). The addition of chemotherapy to local treatments for canine melanoma at oral, digital and cutaneous sites did not lead to a significant increase in survival times. Carboplatin was well tolerated and appeared to have activity against oral melanoma in a subset of patients with gross disease that responded to treatment. Carboplatin with piroxicam could be considered for patients with gross disease when more traditional therapies, such as surgery or radiation therapy, are declined or are not available. In the loco-regional control setting, prospective randomised blinded studies with matched control groups are required to determine if chemotherapy has a role in the treatment of these types of cancer.

Capacidad antioxidante de la sangre de grado (Croton palanostigma sobre la mucosa gástrica, en animales de experimentación

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Miguel Sandoval

2006-09-01

Full Text Available Introducción: El uso de la sangre de grado para el tratamiento de la gastritis y úlceras gástricas se realiza de manera empírica. En investigaciones anteriores hemos observado su capacidad cicatrizante y protectora de la mucosa gástrica, por la estimulación de la secreción de moco, secreción del jugo gástrico sin alterar el pH e incremento de la actividad péptica; por sus componentes, podría además tener capacidad antioxidante, lo que potenciaría su actividad citoprotectora. Objetivo: Determinar la capacidad antioxidante de la sangre de grado (Croton palanostigma sobre la mucosa gástrica en animales de experimentación, por la prueba de TBARS. Diseño: Estudio prospectivo, analítico-experimental y longitudinal. Lugar: Centro de Investigación de Bioquímica y Nutrición Facultad de Medicina UNMSM. Material biológico: Cuarenta ratas albinas machos, entre 220 a 250 g de peso, distribuidas en 4 grupos. Intervenciones: Previo ayuno sólido de 24 h, se administró a las ratas por canulación orogástrica, en dosis única, del modo siguiente: Grupo basal: glucosa 37,5 kcal/kg de peso. Grupo injuria: alcohol 37,7 kcal/kg en glucosa. Grupo control: alcohol 37,7 kcal/kg con piroxicam 10 mg/kg en glucosa. Grupo experimental: alcohol 37,7 kcal/kg con sangre de grado 0,8 mL/kg, en solución de glucosa. Los animales tuvieron agua para consumo ad libitum. Seis horas después, bajo anestesia con éter vaporizado, se practicó una cirugía abdominal, se extrajo el estómago y se obtuvo la porción glandular, se separó una porción representativa de aproximadamente 0,5 g. El tejido gástrico fue homogenizado con buffer fosfato de sodio 50 mmol/L, a pH 7,4. Se determinó la lipoperoxidación midiendo sustancias reactivas al ácido tiobarbitùrico (TBARS, por método espectrofotométrico a 535 nm y se expresó en nmol/gramo de tejido gástrico. Principales medidas de resultados: Capacidad antioxidante de la sangre de grado (Croton palanostigma

Comportamiento de las reacciones adversas a los analgésicos y antiinflamatorios no esteroideos notificadas por el Sistema Cubano de Farmacovigilancia en el 2001

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Giset Jiménez López

2003-12-01

Full Text Available Los fármacos analgésicos y antiinflamatorios no esteroideos comparten algunas actividades terapéuticas y efectos colaterales, su mecanismo de acción está mediado por la inhibición de la ciclooxigenasa (COX 1 y 2, enzima encargada de la biosíntesis de prostaglandinas y otros autacoides similares. En la Unidad Coordinadora de Farmacovigilancia se hace un análisis periódico de las sospechas de reacciones adversas notificadas, y en el 2001 se observó que de los 10 fármacos sospechosos de producir mayor número de reacciones adversas el 50 % corresponde al grupo de los analgésicos y antiinflamatorios no esteroideos, que es a su vez uno de los grupos de mayor consumo en el país. Se realiza una descripción del comportamiento de las sospechas de reacciones adversas relacionadas con aspirina, dipirona, indometacina, ibuprofeno, naproxeno, paracetamol y piroxicam, incluyendo severidad, características demográficas y mecanismo fisiopatológico de estas. En el 2001 se recibieron en la Unidad Coordinadora de Farmacovigilancia 16 195 notificaciones que contenían un total de 33 601 reacciones adversas medicamentosas, de las cuales el 21,5 % correspondió a los analgésicos y antiinflamatorios no esteroideos, grupo este más notificado después de los antimicrobianos. Se encontró que las reacciones de mayor gravedad afectaron a los sistemas hematológico, gastrointestinal y cuerpo como un todo; el sexo femenino y el adulto joven fueron los más afectados. Debido a las reacciones notificadas y a la severidad de estas es necesario mantener vigilancia activa sobre dicho grupo farmacológico y realizar una prescripción adecuada por los médicos con el fin de minimizar el riesgo de sufrir reacciones adversas.The analgesics and nonsteroideal antiinflammatory drugs share some therapeutic activities and side effects. Their action mechanism is mediated by the inhibition of cyclooxygenase (COX 1 and 2, an enzime incharge of the biosynthesis of

Knowledge about Ultraviolet Radiation Hazards and Tanning Behavior of Cosmetology and Medical Students.

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Zuba, Ewelina Bogumiła; Francuzik, Wojciech; Malicki, Przemysław; Osmola-Mańkowska, Agnieszka; Jenerowicz, Dorota

2016-04-01

students reported lower incidence of sunscreen use (83.78% vs. 97.39%; P=0.0019). The age of the first tanning studio visit was also lower for cosmetology students (mean = 16.5 years) than medical students (mean = 17.2 years), (P=0.0290). Figure 1 illustrates the frequency of student tanning studio visits; the difference between groups was significant (P=0.0308). Skin cancers, dysplastic nevi syndrome, and precancerous lesions were reported in the family history by 19 students (10.00%). 12 of those students (63.16%) were also tanning salons users. 85 students (44.74%) reported a history of a sunburn in their childhood and over half of them continue visiting tanning salons. Some American (5) and French (6) studies assessed medical student knowledge and behaviors concerning sun risk and its prevention. The results of these studies indicated that medical school students did not have a satisfactory awareness about sun risk hazards. The French evaluation showed medical student knowledge was comparable to that of the French general population. Studies evaluating Polish student knowledge (7-9) showed ignorance of the term Fitzpatrick's skin phototype. We emphasize this because patients with phototype 1 and 2 are more susceptible to the development of skin cancers (10) and ignorance in this matter may be dangerous. UV rays may promote drug-induced photosensitivity reactions such as phototoxicity and photoallergy (1), with the most common causes being: non-steroidal anti-inflammatory agents (ketoprofen, ibuprofen, piroxicam, diclofenac), cardiovascular drugs (furosemid, amiodarone, thiazides), antibiotics (tetracyclines, ciprofloxacine, sulfonamides), psoralens, and oral contraceptives (11). Our study found deficient knowledge about drugs which may trigger photosensitivity reactions. Cosmetology students reported significantly more risky tanning behavior but did better in knowledge checking questions, which may be explained by their personal interest in this subject or by

A Aspirina e a Asma

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K.S. Babu

2001-03-01

parte dos doentes com AIA, a asma e persistente moderada a grave. Nos casos duvidosos, deve realizar-se a prova de provocação oral com aspirina ou com AINE, que deve ser realizada em mcio hospitalar, pelos riscos que envolve. A prova de provocação nasal com acetilsalicilato de lisina tern igualmente demonstrado ser urn teste seguro, simples e especffico no diagnóstico da AIA.A Iongo prazo, os doentes dcvem cvitar a aspirina e produtos que a contcnham, bem como os AINE's com reacção cruzada à aspirina (ex.: piroxicam, indometacina, diclofenac, naproxeno, ibuprofeno…. Se absolutamente necessários, devem ser preferidos AINE’s com fraca inibição da ciclooxigenase 2 (isofonna desta enzima que e indutfvel durante a inflamação e potencia a sfntese de prostanóides inflamatórios e da ciclooxigenase 1 (isoforrna constitutiva das células no seu estado basal de que e exemplo o acetaminofeno, ou AINE's com inibição rclativa da COX-2, como o nimesulide eo meloxican. Estes fárrnacos só induzem AIA, quando administrados em altas doses ou em doentes com elevada sensibilidade.Quando a terapêutica com AAS ou com AINE’s e essencial ao doente, como acontece nas doenças reumato16gicas ou na profilaxia do enfarte do miocárdia, deve proceder-se á terapêutica de dessensibilização induzindo a tolerancia a estes farrnacos, atraves da ingestão de doses crescentes de aspirina durante 2 a 3 dias, ate atingir 400 mg a 650 mg por dia. A dose de manutenr;ao e habitualmente 100 a 300 mg por dia e deve ser mantida regularmente, caso contrario veritica-se regressao ao nfvel anterior de sensibilidade a este farmaco.As regras gerais de tratamento das exacerbarçães agudas da AIA não di ferem das normas publicadas para o tratamento da asma. Os anti-lcucotrienos (zatirlucast, montelucast, pranlucast e zilcuton são farmacos que atenuam as reacrções brȏnquicas induzidas pela aspirina �