WorldWideScience

Sample records for etoricoxib celecoxib ibuprofen

  1. Cost-Effectiveness Evaluation of Etoricoxib versus Celecoxib and Nonselective NSAIDs in the Treatment of Ankylosing Spondylitis in Norway

    Directory of Open Access Journals (Sweden)

    Jeroen P. Jansen

    2011-01-01

    Full Text Available Objectives. To evaluate the cost-effectiveness of etoricoxib (90 mg relative to celecoxib (200/400 mg, and the nonselective NSAIDs naproxen (1000 mg and diclofenac (150 mg in the initial treatment of ankylosing spondylitis in Norway. Methods. A previously developed Markov state-transition model was used to estimate costs and benefits associated with initiating treatment with the different competing NSAIDs. Efficacy, gastrointestinal and cardiovascular safety, and resource use data were obtained from the literature. Data from different studies were synthesized and translated into direct costs and quality adjusted life years by means of a Bayesian comprehensive decision modeling approach. Results. Over a 30-year time horizon, etoricoxib is associated with about 0.4 more quality adjusted life years than the other interventions. At 1 year, naproxen is the most cost-saving strategy. However, etoricoxib is cost and quality adjusted life year saving relative to celecoxib, as well as diclofenac and naproxen after 5 years of follow-up. For a willingness-to-pay ceiling ratio of 200,000 Norwegian krones per quality adjusted life year, there is a >95% probability that etoricoxib is the most-cost-effective treatment when a time horizon of 5 or more years is considered. Conclusions. Etoricoxib is the most cost-effective NSAID for initiating treatment of ankylosing spondylitis in Norway.

  2. Comparing etoricoxib and celecoxib for preemptive analgesia for acute postoperative pain in patients undergoing arthroscopic anterior cruciate ligament reconstruction: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Glabglay Prapakorn

    2010-10-01

    Full Text Available Abstract Background The efficacy of selective cox-2 inhibitors in postoperative pain reduction were usually compared with conventional non-selective conventional NSAIDs or other types of medicine. Previous studies also used selective cox-2 inhibitors as single postoperative dose, in continued mode, or in combination with other modalities. The purpose of this study was to compare analgesic efficacy of single preoperative administration of etoricoxib versus celecoxib for post-operative pain relief after arthroscopic anterior cruciate ligament reconstruction. Methods One hundred and two patients diagnosed as anterior cruciate ligament injury were randomized into 3 groups using opaque envelope. Both patients and surgeon were blinded to the allocation. All of the patients were operated by one orthopaedic surgeon under regional anesthesia. Each group was given either etoricoxib 120 mg., celecoxib 400 mg., or placebo 1 hour prior to operative incision. Post-operative pain intensity, time to first dose of analgesic requirement and numbers of analgesic used for pain control and adverse events were recorded periodically to 48 hours after surgery. We analyzed the data according to intention to treat principle. Results Among 102 patients, 35 were in etoricoxib, 35 in celecoxib and 32 in placebo group. The mean age of the patients was 30 years and most of the injury came from sports injury. There were no significant differences in all demographic characteristics among groups. The etoricoxib group had significantly less pain intensity than the other two groups at recovery room and up to 8 hours period but no significance difference in all other evaluation point, while celecoxib showed no significantly difference from placebo at any time points. The time to first dose of analgesic medication, amount of analgesic used, patient's satisfaction with pain control and incidence of adverse events were also no significantly difference among three groups. Conclusions

  3. Craving and drug reward: A comparison of celecoxib and ibuprofen in detoxifying opiate addicts

    Directory of Open Access Journals (Sweden)

    sara jafari

    2017-10-01

    Full Text Available OBJECTIVE: Craving for substance abuse is a usual and complicated problem in patients, with opioid addiction, who are in their opioid cessation process. Craving has been added as one of the diagnostic criteria of substance use disorders in DSM-5. AIM: The present trial was intended to compare effects of celecoxib versus ibuprofen in reducing pain and in decreasing the desire to use opiates in patients undergoing opiate detoxification. (n=32. PATIENTS AND METHOD: A total of 32 patients (both inpatients and outpatients, who were undergoing opiate detoxification procedure entered this 4 week study. Subjects who suffered pain due to opiate withdrawal were randomized into two groups; group one received celecoxib 200 milligrams once daily and group two received ibuprofen 400 milligrams four times per day.  Self-reported Desire for Drug Questionnaire (DDQ was utilized at baseline and at the end of the study to evaluate changes in opiate craving. RESULTS: After 4 weeks of treatment, with either ibuprofen or celecoxib, significant improvements in pain and craving were noted in each group. However no significant difference between the two groups was observed after 4 weeks of treatment with celecoxib and ibuprofen. CONCLUSION: The study noted that both celecoxib and ibuprofen, reduce craving in patients with opiate craving after 4 weeks of treatment without any significant difference between the two groups. The results suggest further study of celecoxib and other NSAIDs in the maintenance treatment of opiate craving.

  4. Differential blood pressure effects of ibuprofen, naproxen, and celecoxib in patients with arthritis: the PRECISION-ABPM (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen Ambulatory Blood Pressure Measurement) Trial.

    Science.gov (United States)

    Ruschitzka, Frank; Borer, Jeffrey S; Krum, Henry; Flammer, Andreas J; Yeomans, Neville D; Libby, Peter; Lüscher, Thomas F; Solomon, Daniel H; Husni, M Elaine; Graham, David Y; Davey, Deborah A; Wisniewski, Lisa M; Menon, Venu; Fayyad, Rana; Beckerman, Bruce; Iorga, Dinu; Lincoff, A Michael; Nissen, Steven E

    2017-11-21

    Non-steroidal anti-inflammatory drugs (NSAIDs), both non-selective and selective cyclooxygenase-2 (COX-2) inhibitors, are among the most widely prescribed drugs worldwide, but associate with increased blood pressure (BP) and adverse cardiovascular (CV) events. PRECISION-ABPM, a substudy of PRECISION was conducted at 60 sites, to determine BP effects of the selective COX-2 inhibitor celecoxib vs. the non-selective NSAIDs naproxen and ibuprofen. In this double-blind, randomized, multicentre non-inferiority CV-safety trial, 444 patients (mean age 62 ± 10 years, 54% female) with osteoarthritis (92%) or rheumatoid arthritis (8%) and evidence of or at increased risk for coronary artery disease received celecoxib (100-200 mg bid), ibuprofen (600-800 mg tid), or naproxen (375-500 mg bid) with matching placebos in a 1: 1: 1 allocation, to assess the effect on 24-h ambulatory BP after 4 months. The change in mean 24-h systolic BP (SBP) in celecoxib, ibuprofen and naproxen-treated patients was -0.3 mmHg [95% confidence interval (CI), -2.25, 1.74], 3.7 (95% CI, 1.72, 5.58) and 1.6 mmHg (95% CI, -0.40, 3.57), respectively. These changes resulted in a difference of - 3.9 mmHg (P = 0.0009) between celecoxib and ibuprofen, of - 1.8 mmHg (P = 0.12) between celecoxib and naproxen, and of - 2.1 mmHg (P = 0.08) between naproxen and ibuprofen. The percentage of patients with normal baseline BP who developed hypertension (mean 24-h SBP ≥ 130 and/or diastolic BP ≥ 80 mmHg) was 23.2% for ibuprofen, 19.0% for naproxen, and 10.3% for celecoxib (odds ratio 0.39, P = 0.004 and odds ratio 0.49, P = 0.03 vs. ibuprofen and naproxen, respectively). In PRECISION-ABPM, allocation to the non-selective NSAID ibuprofen, compared with the COX-2 selective inhibitor celecoxib was associated with a significant increase of SBP, and a higher incidence of new-onset hypertension. gov number NCT00346216. Published on behalf of the European

  5. Cardiovascular risk associated with celecoxib or etoricoxib: a meta-analysis of randomized controlled trials which adopted comparison with placebo or naproxen

    NARCIS (Netherlands)

    Vecchis, R. De; Baldi, C.; Biase, G. Di; Ariano, C.; Cioppa, C.; Giasi, A.; Valente, L.; Cantatrione, S.

    2014-01-01

    AIM: The present meta-analysis attempted to assess whether an unfavourable cardiovascular risk profile could be identified in the case of two COX2 selective inhibitors (COXIBs), namely celecoxib and etoricoxib. Based on the data from the literature, our meta-analysis aimed to assess the probability

  6. Celecoxib and Ibuprofen Restore the ATP Content and the Gluconeogenesis Activity in the Liver of Walker-256 Tumor-Bearing Rats

    Directory of Open Access Journals (Sweden)

    Camila Oliveira de Souza

    2015-07-01

    Full Text Available Background/Aims: The main purpose of this study was to investigate the effects of celecoxib and ibuprofen, both non-steroidal anti-inflammatory drugs (NSAIDs, on the decreased gluconeogenesis observed in liver of Walker-256 tumor-bearing rats. Methods: Celecoxib and ibuprofen (both at 25 mg/Kg were orally administered for 12 days, beginning on the same day when the rats were inoculated with Walker-256 tumor cells. Results: Celecoxib and ibuprofen treatment reversed the reduced production of glucose, pyruvate, lactate and urea from alanine as well as the reduced production of glucose from pyruvate and lactate in perfused liver from tumor-bearing rats. Besides, celecoxib and ibuprofen treatment restored the decreased ATP content, increased triacylglycerol levels and reduced mRNA expression of carnitine palmitoyl transferase 1 (CPT1, while ibuprofen treatment restored the reduced mRNA expression of peroxisome proliferator-activated receptor alpha (PPARα in the liver of tumor-bearing rats. Both treatments tended to decrease TNFα, IL6 and IL10 in the liver of tumor-bearing rats. Finally, the treatment with celecoxib, but not with ibuprofen, reduced the growth of Walker-256 tumor. Conclusion: Celecoxib and ibuprofen restored the decreased gluconeogenesis in the liver of Walker-256 tumor-bearing rats. These effects did not involve changes in tumor growth and probably occurred by anti-inflammatory properties of these NSAIDs, which increased expression of genes associated with fatty acid oxidation (PPARα and CPT1 and consequently the ATP production, normalizing the energy status in the liver of tumor-bearing rats.

  7. A comparative study between the efficacy of tramadol, celecoxib and ibuprofen in pain control after root canal therapy of tooth

    Directory of Open Access Journals (Sweden)

    Eshagh A. Saberi

    2011-01-01

    Full Text Available Background: Root canal therapy of teeth can relief the endodontic pain, but post-endodontic pain and discomfort are its undesirable effects. There are many studies on various drugs for alleviation of post-endodontic pain. The aim of this study was to compare the analgesic effect of tramadol, celecoxib and ibuprofen in vital teeth.Materials & Method: In this double blind randomized clinical trial study, 104 patients with vital first mandibular molar tooth were selected. The patients were divided in to four groups, tramadol (A, celecoxib (B, ibuprofen (C and placebo (D. The similar capsules were filled with50mg tramadol HCL, 100mg celecoxib, 400mg ibuprofen and starch . Each patient received randomly one capsule one hour before treatment. If the pain persists, the patient received one tablet of 325 mg acetaminophen every 6 hours. The groups were controlled for 3 days. The data were collected one hour before and 6, 12, 24, 48, 72 hours after treatment. Results were analyzed using kruskal-wallis and Mann-Whitney U tests.Results: The results showed that after 12 (p=0.039 and 24(p=0.024 hours of treatment, tramadol was better in pain relief in comparison with other groups and there was one difference between tramadol and ibuprofen after treatment after 12 hours (p=0.013. But there was no significant deference between drug groups at 6, 48 and 72 hour after treatment.Conclusion: Tramadol prescription in comparison with celecoxib, ibuprofen and placebo has greater analgesic effect after root canal therapy in vital teeth. In addition tramadol may be a good medicine for post-endodontic pain control

  8. Comparison of Preemptive Effects of Celecoxib and Ibuprofen on Postoperative Pain in Addicted Patients Undergoing Lower Abdominal Surgery

    Directory of Open Access Journals (Sweden)

    A. Farhanchi

    2017-10-01

    Full Text Available Background and Objective: Pain is a common postoperative complaint, and the use of analgesics before surgical trauma can effectively prevent peripheral and central sensitization. We aimed to compare the preemptive effects of ibuprofen and celecoxib on post-operative pain after lower abdominal surgery in addicted patients. Materials and Methods: In this clinical trial, after obtaining informed consent, 114 addicted patients undergoing lower abdominal surgery were randomly divided into three groups of 38. The first group was given a 200 mg dose of oral celecoxib, 400 mg of ibuprofen was orally administered to patients in the second group, and the third group was given redsop hcrats as placebo by a nurse who prepared these drugs in the form of capsules. Postoperative pain was assessed by using a 10-cm ruler as the visual analogue scale at intervals of 1 and 6 hours after surgery. Postoperative opioid consumption was recorded in those periods. The obtained data were analyzed using the appropriate statistical tests in SPSS software. Results: Mean pain scores at 1 hour after surgery were not significantly different across the three groups, whereas at 6 hours after surgery, pain scores were significantly lower in the ibuprofen and celecoxib groups in comparison to the placebo group (P=0.001 and P=0.005, respectively. Postoperative nausea and vomiting was not significantly different among the three groups. Conclusion: Despite the significant difference in mean pain scores among the study groups, the opioid consumption doses were not significantly different among the groups. Thus, the preemptive prescription of nonsteroidal anti-inflammatory drugs in addicted patient does not have any noticeable effects.

  9. Efficiency of naproxen/esomeprazole in association for osteoarthrosis treatment in Spain.

    Science.gov (United States)

    Capel, Margarita; Tornero, Jesús; Zamorano, José Luis; Oyagüez, Itziar; Casado, Miguel Ángel; Sánchez-Covisa, Joaquín; Lanas, Angel

    2014-01-01

    To assess, from the perspective of the National Healthcare System, the efficiency of a fixed-dose combination of naproxen and esomeprazole (naproxen/esomeprazole) in the treatment of osteoarthritis (OA) compared to other NSAID, alone or in combination with a proton pump inhibitor (PPI). A Markov model was used; it included different health states defined by gastrointestinal (GI) events: dyspepsia, symptomatic or complicated ulcer; or cardiovascular (CV) events: myocardial infarction, stroke or heart failure. The model is similar to the one used by NICE in its NSAID evaluation of OA published in 2008. The total costs (€, 2012), including drug and event-related costs, and the health outcomes expressed in quality-adjusted life years (QALY) were estimated in patients with increased GI risk, aged 65 or over, for a 1-year time horizon and a 6-month treatment with celecoxib (200mg/day), celecoxib+PPI, diclofenac (150mg/day)+PPI, etoricoxib (60mg/day), etoricoxib+PPI, ibuprofen (1,800mg/day)+PPI, naproxen (1,000mg/day)+PPI or naproxen/esomeprazole (naproxen 1,000mg/esomeprazole 40mg/day). The selected PPI was omeprazole (20mg/day). Naproxen/esomeprazole was a dominant strategy (more effective and less costly) compared to celecoxib, etoricoxib and diclofenac+PPI. Celecoxib+PPI and etoricoxib+PPI were more effective. Considering a cost-effectiveness threshold of €30,000 per additional QALY, naproxen/esomeprazole was cost-effective compared to ibuprofen+PPI and naproxen+PPI with incremental cost-effectiveness ratios (ICER) of €15,154 and €5,202 per additional QALY, respectively. A fixed-dose combination of naproxen and esomeprazole is a cost-effective, and even dominant, alternative compared to other options in OA patients with increased GI risk. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  10. Safety of Etoricoxib, Celecoxib, and Nonselective Nonsteroidal Antiinflammatory Drugs in Ankylosing Spondylitis and Other Spondyloarthritis Patients

    DEFF Research Database (Denmark)

    Kristensen, L E; Jakobsen, A K; Askling, J

    2015-01-01

    OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular, and cardio......OBJECTIVE: Safety data regarding the use of etoricoxib and other nonsteroidal antiinflammatory drugs (NSAIDs) in ankylosing spondylitis (AS) and other spondyloarthritis (SpA) patients are rather limited. Our objective was to estimate and compare rates of gastrointestinal, renovascular...

  11. Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    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.

  12. Etoricoxib (arcoxia in rheumatology

    Directory of Open Access Journals (Sweden)

    Fatima Magomedovna Kudaeva

    2011-06-01

    Full Text Available The paper gives information on the selective COX-2 inhibitor etoricoxib registered for use in many countries of the world. It gives a brief description of a few key trials of the efficacy and tolerability of etoricoxib in rheumatology

  13. Etoricoxib (arcoxia in rheumatology

    Directory of Open Access Journals (Sweden)

    Fatima Magomedovna Kudaeva

    2011-01-01

    Full Text Available The paper gives information on the selective COX-2 inhibitor etoricoxib registered for use in many countries of the world. It gives a brief description of a few key trials of the efficacy and tolerability of etoricoxib in rheumatology

  14. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis.

    Science.gov (United States)

    Trelle, Sven; Reichenbach, Stephan; Wandel, Simon; Hildebrand, Pius; Tschannen, Beatrice; Villiger, Peter M; Egger, Matthias; Jüni, Peter

    2011-01-11

    To analyse the available evidence on cardiovascular safety of non-steroidal anti-inflammatory drugs. Network meta-analysis. Bibliographic databases, conference proceedings, study registers, the Food and Drug Administration website, reference lists of relevant articles, and reports citing relevant articles through the Science Citation Index (last update July 2009). Manufacturers of celecoxib and lumiracoxib provided additional data. All large scale randomised controlled trials comparing any non-steroidal anti-inflammatory drug with other non-steroidal anti-inflammatory drugs or placebo. Two investigators independently assessed eligibility. The primary outcome was myocardial infarction. Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data. 31 trials in 116 429 patients with more than 115 000 patient years of follow-up were included. Patients were allocated to naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib, or placebo. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction (rate ratio 2.12, 95% credibility interval 1.26 to 3.56), followed by lumiracoxib (2.00, 0.71 to 6.21). Ibuprofen was associated with the highest risk of stroke (3.36, 1.00 to 11.6), followed by diclofenac (2.86, 1.09 to 8.36). Etoricoxib (4.07, 1.23 to 15.7) and diclofenac (3.98, 1.48 to 12.7) were associated with the highest risk of cardiovascular death. Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Naproxen seemed least harmful. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug.

  15. The Effect of Etoricoxib on Hepatic Ischemia-Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Celalettin Semih Kunak

    2015-01-01

    Full Text Available Ischemia-reperfusion (I/R damage is known to be a pathological process which continues with the increase of oxidants and expands with the inflammatory response. There is not any study about protective effect of etoricoxib on the liver I/R damage in literature. Objective. This study investigates the effect of etoricoxib on oxidative stress induced by I/R of the rat liver. Material and Methods. Experimental animals were divided into four groups as liver I/R control (LIRC, 50 mg/kg etoricoxib + liver I/R (ETO-50, 100 mg/kg etoricoxib + liver I/R (ETO-100, and healthy group (HG. ETO-50 and ETO-100 groups were administered etoricoxib, while LIRC and HG groups were orally given distilled water by gavage. Hepatic artery was clamped for one hour to provide ischemia, and then reperfusion was provided for 6 hours. Oxidant, antioxidant, and COX-2 gene expressions were studied in the liver tissues. ALT and AST were measured. Results. Etoricoxib in 50 and 100 mg/kg doses changed the levels of oxidant/antioxidant parameters such as MDA, MPO, tGSH, GSHRd, GST, SOD, NO, and 8-OH/Gua in favour of antioxidants. Furthermore, etoricoxib prevented increase of COX-2 gene expression and ALT and AST levels. This important protective effect of etoricoxib on the rat liver I/R can be tested in the clinical setting.

  16. WHY IS THE STUDY OF THE COMPLEX SAFETY OF CELECOXIB FOR ARTHRITIS, WHICH IS CALLED PRECISION, LAST BUT NOT LEAST?

    Directory of Open Access Journals (Sweden)

    Yu. V. Muravyev

    2017-01-01

    Full Text Available The paper discusses the results of the long-term PRECISION study specially designed for the prospective comparative evaluation primarily of the cardiovascular safety of celecoxib, ibuprofen, and naproxen, which are long used for the treatment of pain in patients with arthritis. 

  17. Celecoxib versus a non-selective NSAID plus proton-pump inhibitor: what are the considerations?.

    Science.gov (United States)

    Chen, Judy T; Pucino, Frank; Resman-Targoff, Beth H

    2006-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are extensively used worldwide. However, associated adverse gastrointestinal effects (NSAID gastropathy) such as bleeding, perforation and obstruction result in considerable morbidity, mortality, and expense. Although it is essential to employ gastroprotective strategies to minimize these complications in patients at risk, controversy remains on whether celecoxib alone or a non-selective NSAID in conjunction with a proton-pump inhibitor (PPI) is a superior choice. Recent concerns regarding potential cardiovascular toxicities associated with cox-2 selective inhibitors may favor non-selective NSAID/PPI co-therapy as the preferred choice. Concomitant use of low-dose aspirin with any NSAID increases the risk of gastrointestinal complications and diminishes the improved gastrointestinal safety profile of celecoxib; whereas use of ibuprofen plus PPI regimens may negate aspirin's antiplatelet benefits. Evidence shows that concurrent use of a non-selective NSAID (such as naproxen) plus a PPI is as effective in preventing NSAID gastropathy as celecoxib, and may be more cost-effective. Patients failing or intolerant to this therapy would be candidates for celecoxib at the lowest effective dose for the shortest duration of time. Potential benefits from using low-dose celecoxib with a PPI in patients previously experiencing bleeding ulcers while taking NSAIDs remains to be proven. An evidence-based debate is presented to assist clinicians with the difficult decision-making process of preventing NSAID gastropathy while minimizing other complications.

  18. Etoricoxib in the Prevention of Rat Mammary Carcinogenesis

    Directory of Open Access Journals (Sweden)

    P. Orendáš

    2007-01-01

    Full Text Available Several experimental studies suggest that non-steroidal antiinflammatory drugs have chemopreventive effects in mammary carcinogenesis. In this study, tumour suppressive effects of a selective inhibitor of cyclooxygenase-2 (COX-2 etoricoxib in the prevention of N-methyl-Nnitrosourea (NMU-induced mammary carcinogenesis in Sprague-Dawley rats were evaluated. Etoricoxib was administered in the diet, at two concentrations: 1 0.01 mg/g (ETO 0.001% and 2 0.025 mg/g (ETO 0.0025%. Although the chemopreventive effects were not statistically significant, remarkable tumour suppressive effects with the concentration of ETO 0.0025% were recorded. The incidence decreased by 4.31% and tumour frequency per group decreased by 6.67% when compared to the control group. Latency (the period from carcinogen administration to the first tumour appearance increased by 7.28% in dose-dependent manner. The results of our experiments point to dose-dependent tumour suppressive effects of a higher concentration of etoricoxib (ETO 0.0025% when compared to the control group. They suggest that higher etoricoxib concentrations may enhance its tumour suppressive effects.

  19. Gastrointestinal safety of etoricoxib in osteoarthritis and rheumatoid arthritis: A meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xiaoting Feng

    Full Text Available To ascertain if etoricoxib increases the risk of gastrointestinal adverse events (GAEs compared with placebo, diclofenac, and naproxen in the treatment of patients with osteoarthritis (OA or rheumatoid arthritis (RA.Studies were searched in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials from inception to August 2017. Randomized Clinical Trials (RCTs that compared etoricoxib with placebo and other active drug for patients with OA or RA and reported data on gastrointestinal safety (which is of interest to patients and clinicians were included. The follow-up time window for GAEs was defined as within 28 days subsequent to the last dose of study medication. A meta-analysis was conducted using a fixed-effect model. Risk ratios (RRs and 95% confidence intervals (CIs were measured.We found nine randomized clinical trials (RCTs that included information on gastrointestinal safety during follow-up time. Among them, five RCTs compared etoricoxib with placebo, four RCTs compared etoricoxib with diclofenac, and three RCTs compared etoricoxib with naproxen. Etoricoxib did not increase the risk of GAEs compared with placebo. Compared with diclofenac and naproxen, etoricoxib reduced the GAE risk (RR, 0.67; 95% CI, 0.59-0.76; p < 0.00001; 0.59; 0.48-0.72; < 0.00001 during follow-up time.In patients with OA or RA, etoricoxib did not increase the GAE risk compared with placebo, but reduced the GAE risk effectively compared with diclofenac and naproxen during follow-up time.

  20. Comparison of etoricoxib and indomethacin for the treatment of experimental periodontitis in rats

    Directory of Open Access Journals (Sweden)

    M.C.F. Azoubel

    2007-01-01

    Full Text Available We investigated the effect of etoricoxib, a selective cyclooxygenase-2 inhibitor, and indomethacin, a non-selective cyclooxygenase inhibitor, on experimental periodontitis, and compared their gastrointestinal side effects. A ligature was placed around the second upper left molars of female Wistar rats (160 to 200 g. Animals (6 per group were treated daily with oral doses of 3 or 9 mg/kg etoricoxib, 5 mg/kg indomethacin, or 0.2 mL saline, starting 5 days after the induction of periodontitis, when bone resorption was detected, until the sacrifice on the 11th day. The weight and survival rate were monitored. Alveolar bone loss (ABL was measured as the sum of distances between the cusp tips and the alveolar bone. The gastric mucosa was examined macroscopically and the periodontium and gastric and intestinal mucosa were examined by histopathology. The ongoing ABL was significantly inhibited (P < 0.05 by 3 and 9 mg/kg etoricoxib and by indomethacin: control = 4.08 ± 0.47 mm; etoricoxib (3 mg/kg = 1.89 ± 0.26 mm; etoricoxib (9 mg/kg = 1.02 ± 0.14 mm; indomethacin = 0.64 ± 0.15 mm. Histopathology of periodontium showed that etoricoxib and indomethacin reduced inflammatory cell infiltration, ABL, and cementum and collagen fiber destruction. Macroscopic and histopathological analysis of gastric and intestinal mucosa demonstrated that etoricoxib induces less damage than indomethacin. Animals that received indomethacin presented weight loss starting on the 7th day, and higher mortality rate (58.3% compared to etoricoxib (0%. Treatment with etoricoxib, even starting when ABL is detected, reduces inflammation and cementum and bone resorption, with fewer gastrointestinal side effects.

  1. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies.

    Directory of Open Access Journals (Sweden)

    Patricia McGettigan

    2011-09-01

    Full Text Available BACKGROUND: Randomised trials have highlighted the cardiovascular risks of non-steroidal anti-inflammatory drugs (NSAIDs in high doses and sometimes atypical settings. Here, we provide estimates of the comparative risks with individual NSAIDs at typical doses in community settings. METHODS AND FINDINGS: We performed a systematic review of community-based controlled observational studies. We conducted comprehensive literature searches, extracted adjusted relative risk (RR estimates, and pooled the estimates for major cardiovascular events associated with use of individual NSAIDs, in different doses, and in populations with low and high background risks of cardiovascular events. We also compared individual drugs in pair-wise (within study analyses, generating ratios of RRs (RRRs. Thirty case-control studies included 184,946 cardiovascular events, and 21 cohort studies described outcomes in >2.7 million exposed individuals. Of the extensively studied drugs (ten or more studies, the highest overall risks were seen with rofecoxib, 1.45 (95% CI 1.33, 1.59, and diclofenac, 1.40 (1.27, 1.55, and the lowest with ibuprofen, 1.18 (1.11, 1.25, and naproxen, 1.09 (1.02, 1.16. In a sub-set of studies, risk was elevated with low doses of rofecoxib, 1.37 (1.20, 1.57, celecoxib, 1.26 (1.09, 1.47, and diclofenac, 1.22 (1.12, 1.33, and rose in each case with higher doses. Ibuprofen risk was seen only with higher doses. Naproxen was risk-neutral at all doses. Of the less studied drugs etoricoxib, 2.05 (1.45, 2.88, etodolac, 1.55 (1.28, 1.87, and indomethacin, 1.30 (1.19, 1.41, had the highest risks. In pair-wise comparisons, etoricoxib had a higher RR than ibuprofen, RRR = 1.68 (99% CI 1.14, 2.49, and naproxen, RRR = 1.75 (1.16, 2.64; etodolac was not significantly different from naproxen and ibuprofen. Naproxen had a significantly lower risk than ibuprofen, RRR = 0.92 (0.87, 0.99. RR estimates were constant with different background risks for

  2. Cardiovascular and hematologic effects produced by chronic treatment with etoricoxib in normotensive rats Efeitos cardiovasculares e hematológicos produzidos pelo tratamento crônico com etoricoxib em ratos normotensos

    Directory of Open Access Journals (Sweden)

    Nilo César do Vale Baracho

    2009-06-01

    Full Text Available PURPOSE: Evaluate the cardiovascular and hematological effects produced by chronic treatment with two dosis of etoricoxib in Wistar normotensive rats. METHODS: Thirty rats have been used and divided into one control group and two etoricoxib (10mg/kg and 30mg/kg treatments groups for 60 days. The mean arterial pressure (MAP was taken during the whole experimental period and at the end of this period, under anesthesia blood samples were taken, and further the withdrawn of the aorta, heart, brain, liver, and kidneys for the anatomopathologic study. RESULTS: The treatment with etoricoxib (30mg/Kg produced a significant increase of the MAP from the 28th day of the experiment and from the platelets when compared to the control group and to the group treated with 10mg/Kg, besides producing a highly significant difference in hematocrit and in the red blood cells in relation to the control group. On the other hand the treatment with etoricoxib has not caused histopathological changes when compared to the control. CONCLUSION: These data show that the chronic treatment with etoricoxib leads to increase of the MAP, and to important hematological changes which seem to be associated to the hemoconcentration although not producing anatomopathological significant changes.OBJETIVO: Avaliar os efeitos cardiovasculares e hematológicos produzidos pelo tratamento crônico com duas doses de etoricoxib em ratos Wistar normotensos. MÉTODOS: Foram utilizados 30 ratos divididos em um grupo controle e dois grupos tratamentos (10mg/kg e 30mg/kg de etoricoxib por 60 dias. A pressão arterial média (PAM dos animais foi aferida durante todo o período experimental e, ao final deste, sob anestesia, foram coletadas amostras de sangue, além da retirada da aorta, coração, cérebro, fígado e rins para estudo anatomopatológico. RESULTADOS: O tratamento com etoricoxib (30mg/Kg produziu aumento significativo da PAM a partir do 28° dia do experimento e das plaquetas quando

  3. Optimization of fast dissolving etoricoxib tablets prepared by sublimation technique

    OpenAIRE

    Patel D; Patel M

    2008-01-01

    The purpose of this investigation was to develop fast dissolving tablets of etoricoxib. Granules containing etoricoxib, menthol, crospovidone, aspartame and mannitol were prepared by wet granulation technique. Menthol was sublimed from the granules by exposing the granules to vacuum. The porous granules were then compressed in to tablets. Alternatively, tablets were first prepared and later exposed to vacuum. The tablets were evaluated for percentage friability and disintegration time. A 3 2 ...

  4. The effect of etoricoxib premedication on postoperative analgesia requirement in orthopedic and trauma patients

    International Nuclear Information System (INIS)

    Siddiqui, Ahsan K.; Al-Ghamdi, Abdulmohsin A.; Mowafi, Hany A.; Ismail, Salah A.; Sadat-Ali, M.; Al-Dakheel, Dakheel A.

    2008-01-01

    We have hypothesized that etoricoxib premedication would reduce the need for additional opioids following orthopedic trauma surgery. A double blind, controlled study, conducted in King Fahd University Hospital, King Faisal University, Dammam, Kingdom of Saudi Arabia. After obtaining the approval of Research and Ethics Committee and written consent, 200 American Society of Anesthesiology grade I and II patients that underwent elective upper limb or lower limb fracture fixation surgeries during the period from August 2005 to October 2007 were studied. Patients were randomly premedicated using 120 mg of etoricoxib or placebo n=100, each. To alleviate postoperative pain, a patient controlled analgesia device was programmed to deliver one mg of morphine intravenously locked lockout time, 6 minutes. Visual analog scale and total postoperative morphine consumption over 24 hours and the adverse effects were recorded. One hundred patients in each group completed the study period. Etoricoxib premedication provides a statistically significant postoperative morphine sparing effect over 24 hours postoperatively. Total morphine consumption was 44.2 (8.2) in the placebo and 35.17 mg in the etoricoxib groups p<0.001. The incidence of nausea and vomiting requiring treatment was lower in the etoricoxib group. p=0.014. The postoperative blood loss was similar in both groups. Etoricoxib is a suitable premedication before traumatic orthopedic surgery as it enhanced postoperative analgesia and reduced the need for morphine. (author)

  5. Ibuprofen administration attenuates serum TNF-α levels, hepatic glutathione depletion, hepatic apoptosis and mouse mortality after Fas stimulation

    International Nuclear Information System (INIS)

    Cazanave, Sophie; Vadrot, Nathalie; Tinel, Marina; Berson, Alain; Letteron, Philippe; Larosche, Isabelle; Descatoire, Veronique; Feldmann, Gerard; Robin, Marie-Anne; Pessayre, Dominique

    2008-01-01

    Fas stimulation recruits neutrophils and activates macrophages that secrete tumor necrosis factor-α (TNF-α), which aggravates Fas-mediated liver injury. To determine whether nonsteroidal anti-inflammatory drugs modify these processes, we challenged 24-hour-fasted mice with the agonistic Jo2 anti-Fas antibody (4 μg/mouse), and treated the animals 1 h later with saline or ibuprofen (250 mg/kg), a dual cyclooxygenase (COX)-1 and COX-2 inhibitor. Ibuprofen attenuated the Jo2-mediated recruitment/activation of myeloperoxidase-secreting neutrophils/macrophages in the liver, and attenuated the surge in serum TNF-α. Ibuprofen also minimized hepatic glutathione depletion, Bid truncation, caspase activation, outer mitochondrial membrane rupture, hepatocyte apoptosis and the increase in serum alanine aminotransferase (ALT) activity 5 h after Jo2 administration, to finally decrease mouse mortality at later times. The concomitant administration of pentoxifylline (decreasing TNF-α secretion) and infliximab (trapping TNF-α) likewise attenuated the Jo2-mediated increase in TNF-α, the decrease in hepatic glutathione, and the increase in serum ALT activity 5 h after Jo2 administration. The concomitant administration of the COX-1 inhibitor, SC-560 (10 mg/kg) and the COX-2 inhibitor, celecoxib (40 mg/kg) 1 h after Jo2 administration, also decreased liver injury 5 h after Jo2 administration. In contrast, SC-560 (10 mg/kg) or celecoxib (40 or 160 mg/kg) given alone had no significant protective effects. In conclusion, secondary TNF-α secretion plays an important role in Jo2-mediated glutathione depletion and liver injury. The combined inhibition of COX-1 and COX-2 by ibuprofen attenuates TNF-α secretion, glutathione depletion, mitochondrial alterations, hepatic apoptosis and mortality in Jo2-treated fasted mice

  6. Cardiovascular safety of etoricoxib

    Directory of Open Access Journals (Sweden)

    Viktoriya Georgievna Barskova

    2011-01-01

    Full Text Available Meticulous attention is paid to the cardiovascular safety of nonsteroidal anti-inflammatory drugs (NSAIDs, the so-called selective cyclooxy-genase 2 (COX-2 inhibitors in particular. The author considers precisely this matter in case of Russia's recent NSAID etoricoxib that has been tested along with other most studied medications from this group, by applying one of the latest meta-analyses. The EULAR recommendations to use NSAIDs are given.

  7. Pharmacokinetic equivalence study of nonsteroidal anti-inflammatory drug etoricoxib

    Directory of Open Access Journals (Sweden)

    Tjandrawinata RR

    2018-04-01

    Full Text Available Raymond R Tjandrawinata,1 Arini Setiawati,2 Dwi Nofiarny,1 Liana W Susanto,1 Effi Setiawati3 1Dexa Laboratories of Biomolecular Sciences Unit, Dexa Medica Group, Cikarang, West Java, Indonesia; 2Department of Pharmacology and Therapeutics, Medical Faculty, University of Indonesia, Jakarta, Indonesia; 3Bioavailability and Bioequivalence Laboratory Unit, PT Equilab International, Jakarta, Indonesia Purpose: The current study aimed to evaluate whether a generic product of etoricoxib 120 mg film-coated tablet (the test drug was bioequivalent to the reference product (Arcoxia® film-coated tablet 120 mg.Methods: This was a randomized, open-label, two-sequence, crossover study under fasting condition, with a 14-day washout period, involving 26 healthy adult male and female subjects. Blood samples were taken and analyzed for plasma concentrations of etoricoxib (Chemical Abstracts Service [CAS] 202409-33-4 using a high-pressure liquid chromatography–ultraviolet detector (HPLC-UV system capable of measuring etoricoxib concentrations ranging from 5.00 to 5002.90 ng/mL, with the lowest limit of quantitation of 5.00 ng/mL. A noncompartmental method was used to determine the pharmacokinetic parameters of a single-dose administration of the drug, including the area under plasma concentration–time curve from time zero to the time of last observed concentration (AUC0-t, the area under plasma concentration–time curve from time zero to infinity (AUC0-∞, the maximum plasma concentration (Cmax, the time to reach the maximum plasma concentration (tmax, and the terminal half-life (t½.Results: After a single-dose administration of etoricoxib 120 mg film-coated tablet, the mean (SD values for the AUC0-72h and Cmax of the test drug were 45913.42 (13142.19 ng·h/mL and 3155.93 (752.81 ng/mL, respectively; the values for the reference drug were 44577.20 (13541.85 ng⋅h/mL and 2915.13 (772.81 ng/mL, respectively. The geometric mean ratios (90% CIs of the test

  8. Etoricoxib - preemptive and postoperative analgesia (EPPA in patients with laparotomy or thoracotomy - design and protocols

    Directory of Open Access Journals (Sweden)

    Hatz Rudolf

    2010-05-01

    Full Text Available Abstract Background and Objective Our objective was to report on the design and essentials of the Etoricoxib protocol- Preemptive and Postoperative Analgesia (EPPA Trial, investigating whether preemptive analgesia with cox-2 inhibitors is more efficacious than placebo in patients who receive either laparotomy or thoracotomy. Design and Methods The study is a 2 × 2 factorial armed, double blinded, bicentric, randomised placebo-controlled trial comparing (a etoricoxib and (b placebo in a pre- and postoperative setting. The total observation period is 6 months. According to a power analysis, 120 patients scheduled for abdominal or thoracic surgery will randomly be allocated to either the preemptive or the postoperative treatment group. These two groups are each divided into two arms. Preemptive group patients receive etoricoxib prior to surgery and either etoricoxib again or placebo postoperatively. Postoperative group patients receive placebo prior to surgery and either placebo again or etoricoxib after surgery (2 × 2 factorial study design. The Main Outcome Measure is the cumulative use of morphine within the first 48 hours after surgery (measured by patient controlled analgesia PCA. Secondary outcome parameters include a broad range of tests including sensoric perception and genetic polymorphisms. Discussion The results of this study will provide information on the analgesic effectiveness of etoricoxib in preemptive analgesia and will give hints on possible preventive effects of persistent pain. Trial registration NCT00716833

  9. A multinational randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arthritis [ISRCTN25142273

    Directory of Open Access Journals (Sweden)

    Zhao Peng

    2002-05-01

    Full Text Available Abstract Background Etoricoxib is a highly selective COX-2 inhibitor which was evaluated for the treatment of rheumatoid arthritis (RA. Methods Double-blind, randomized, placebo and active comparator-controlled, 12-week study conducted at 67 sites in 28 countries. Eligible patients were chronic NSAID users who demonstrated a clinical worsening of arthritis upon withdrawal of prestudy NSAIDs. Patients received either placebo, etoricoxib 90 mg once daily, or naproxen 500 mg twice daily (2:2:1 allocation ratio. Primary efficacy measures included direct assessment of arthritis by counts of tender and swollen joints, and patient and investigator global assessments of disease activity. Key secondary measures included the Stanford Health Assessment Questionnaire, patient global assessment of pain, and the percentage of patients who achieved ACR20 responder criteria response (a composite of pain, inflammation, function, and global assessments. Tolerability was assessed by adverse events and routine laboratory evaluations. Results 1171 patients were screened, 891 patients were randomized (N = 357 for placebo, N = 353 for etoricoxib, and N = 181 for naproxen, and 687 completed 12 weeks of treatment (N = 242 for placebo, N = 294 for etoricoxib, and N = 151 for naproxen. Compared with patients receiving placebo, patients receiving etoricoxib and naproxen showed significant improvements in all efficacy endpoints (p Conclusions In this study, etoricoxib 90 mg once daily was more effective than placebo and similar in efficacy to naproxen 500 mg twice daily for treating patients with RA over 12 weeks. Etoricoxib 90 mg was generally well tolerated in RA patients.

  10. Etoricoxib in the treatment of osteoarthritis over 52-weeks: a double-blind, active-comparator controlled trial [NCT00242489

    Directory of Open Access Journals (Sweden)

    Olaleye Joseph

    2005-12-01

    Full Text Available Abstract Background The aim of this study was to evaluate the long-term efficacy and tolerability of etoricoxib, a COX-2 selective inhibitor, in osteoarthritis (OA patients. Methods A double-blind, randomized, multicenter study was conducted in 617 patients with OA of the knee. The base study was 14 weeks in duration and consisted of 2 parts; in Part I (6 weeks, patients were allocated to once daily oral etoricoxib 5, 10, 30, 60, 90 mg or placebo. In Part II (8 weeks; the placebo, etoricoxib 5 and 10 mg groups were reallocated to etoricoxib 30, 60, or 90 mg qd or diclofenac 50 mg t.i.d. Treatment was continued for consecutive 12 and 26 week extensions. Primary efficacy endpoints were the WOMAC VA 3.0 pain subscale and investigator global assessment of disease status. Safety and tolerability were assessed by collecting adverse events throughout the study. Results Compared with placebo, the etoricoxib groups displayed significant (p Conclusion In this extension study, etoricoxib, at doses ranging from 30 to 90 mg, demonstrated a maintenance of significant clinical efficacy in patients with OA through 52 weeks of treatment. Etoricoxib displayed clinical efficacy similar to diclofenac 150 mg and was generally well tolerated.

  11. ETORICOXIB IS A NEW SELECTIVE CYCLOOXYGENASE-2 INHIBITOR

    Directory of Open Access Journals (Sweden)

    A E Karateev

    2009-01-01

    Full Text Available The paper provides the clinical characteristics of etoricoxib (Arcoxia, a new selective cyclooxygenase-2 inhibitor having unique properties, which permits it to be distinguished among other nonsteroidal anti-inflammatory agents.

  12. ETORICOXIB IS A NEW SELECTIVE CYCLOOXYGENASE-2 INHIBITOR

    Directory of Open Access Journals (Sweden)

    A E Karateev

    2009-06-01

    Full Text Available The paper provides the clinical characteristics of etoricoxib (Arcoxia, a new selective cyclooxygenase-2 inhibitor having unique properties, which permits it to be distinguished among other nonsteroidal anti-inflammatory agents.

  13. Effectiveness of tramadol/paracetamol compared with etoricoxib as ...

    African Journals Online (AJOL)

    paracetamol combination when compared with etoricoxib as postoperative analgesia following day care surgery. Design: This was a prospective, randomised, single-blind study. Setting and subjects: Sixty-two patients were randomised to receive ...

  14. Etoricoxib-induced pretibial erythema and edema

    Directory of Open Access Journals (Sweden)

    Pramod Kumar

    2015-01-01

    Full Text Available Cyclooxygenase inhibitors were developed in the quest of enhanced analgesic efficacy devoid of gastric side effects. Etoricoxib is a second-generation cox-2 inhibitor and as its use increases so do the reports of side effects. We report a case of extoricoxib-induced pretibial erythema and edema; and review the literature.

  15. Bioavailability of ibuprofen following oral administration of standard ibuprofen, sodium ibuprofen or ibuprofen acid incorporating poloxamer in healthy volunteers

    OpenAIRE

    Dewland, Peter M; Reader, Sandie; Berry, Phillip

    2009-01-01

    Background The aim of this study was to compare the pharmacokinetic properties of sodium ibuprofen and ibuprofen acid incorporating poloxamer with standard ibuprofen acid tablets. Methods Twenty-two healthy volunteers were enrolled into this randomised, single-dose, 3-way crossover, open-label, single-centre, pharmacokinetic study. After 14 hours' fasting, participants received a single dose of 2 × 200 mg ibuprofen acid tablets (standard ibuprofen), 2 × 256 mg ibuprofen sodium dihydrate table...

  16. Perioperative use of etoricoxib reduces pain and opioid side-effects after total abdominal hysterectomy

    DEFF Research Database (Denmark)

    Viscusi, Eugene R; Frenkl, Tara L; Hartrick, Craig T

    2012-01-01

    Abstract Objective: To evaluate the effects of two different doses of etoricoxib delivered perioperatively compared with placebo and standard pain management on pain at rest, pain with mobilization, and use of additional morphine/opioids postoperatively. Research design and methods: In this double......-blind, placebo-controlled, randomized clinical trial, we evaluated postoperative pain following total abdominal hysterectomy over 5 days in patients receiving placebo or etoricoxib administered 90 min prior to surgery and continuing postoperatively. Patients were randomly assigned to receive either placebo (n...... in the active treatment groups by ~10 hours vs. placebo. A greater proportion of patients on etoricoxib (10-30% greater than placebo) achieved mild levels of pain with movement, defined as pain pain measurements were not designated...

  17. Etoricoxib improves osteoarthritis pain relief, joint function, and quality of life in the extreme elderly

    Directory of Open Access Journals (Sweden)

    Wen-Nan Huang

    2018-02-01

    Full Text Available Etoricoxib is a selective cyclooxygenase-2 inhibitor, with a lower risk of gastrointestinal toxicity compared to traditional nonsteroidal anti-inflammatory drugs (NSAIDs. We evaluated the effectiveness and tolerability of etoricoxib in extremely elderly patients with chronic pain due to osteoarthritis (OA. A prospective, single-center, single-arm study was conducted, enrolling 19 extremely elderly men with OA (mean age 85.9, range 79-96 years, who responded inadequately to NSAIDs or other analgesics. Patients were switched to etoricoxib, 60 mg once daily for 4 weeks, without prior medication washout. Data were recorded before and after etoricoxib treatment. The primary endpoint was improvement in pain, assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC after the 4-week treatment. Other endpoints included the Brief Pain Inventory Short Form (BPI-SF, Treatment Satisfaction Questionnaire for Medication (TSQM, Short Form 36 (SF36, and European Quality of Life-5 Dimensions (EQ-5D. Safety and tolerability were assessed by collecting adverse events data. Pain and disability scores measured by WOMAC index were lower after treatment (pain, p ≤ 0.001; disability, p = 0.020. BPI-SF showed a significant improvement in joint function when walking and performing normal work (walking, p = 0.021; normal work, p = 0.030. SF36 scores improved for 7 out of 11 items after etoricoxib treatment (#1, p = 0.032; #4, p = 0.026; #5, p = 0.017; #6, p = 0.008; #7, p = 0.009; #8, p = 0.013; and #10, p = 0.038. EQ-5D showed a significant improvement in visual analogue scale scores (p = 0.036. TSQM results demonstrated a higher patient perception of overall satisfaction. No adverse events were reported. Pain relief, joint function, quality of life, and treatment satisfaction improved significantly in elderly patients with OA after etoricoxib administration.

  18. Preparation and characterization of etoricoxib solid dispersions using lipid carriers by spray drying technique

    OpenAIRE

    Chauhan, Bhaskar; Shimpi, Shyam; Paradkar, Anant

    2005-01-01

    The basic objectives of this study were to prepare and characterize solid dispersions of poorly water-soluble drug etoricoxib using lipid carriers by spray drying technique. The properties of solid dispersions were studied by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), differential scanning calorimetry (DSC), hotstage microscopy (HSM), radiograph powder diffraction (XRPD), and dissolution studies. The absence of etoricoxib peaks in XRPD profiles of solid dispersions ...

  19. Use of etoricoxib in patients with gout in real clinical practice

    Directory of Open Access Journals (Sweden)

    M S Eliseyev

    2013-01-01

    Full Text Available Objective: to evaluate the efficacy and safety of etoricoxib (Arcoxia ® in gouty patients with an acute arthritis attack in real clinical practice. Subjects and methods. Thirty patients (25 men and 5 women; mean age 52.4±13.5 years with crystal-verified gout participated in the pilot open-label study of the patients with arthritis, including those who had taken other nonsteroidal anti-inflammatory drugs (NSAIDs without any effect. All the patients received etoricoxib (Arcoxia ® in a dose of 120 mg/day for 7 days and, if arthritis persisted, in a dose of 90 mg/day for 7 more days. The authors estimated an articular index, swelling and hyperemia indices, resting and movement pain by a visual analogue scale (VAS, therapy tolerance in the patient's opinion before and 7 days after therapy and, in the patients taking etoricoxib for 14 days, after 14 days of therapy. Biochemical and clinical blood tests were carried out at the first and subsequent visits. Results. Seven days after therapy, an arthritis attack was abolished in 24 of the 28 patients, following 14 days, arthritis persisted only in 1 patient, but the number of affected joints reduced from 8 to 2. Following 7 days, there was a reduction in the mean erythrocyte sedimentation rate from 37.2+10.2 (before etoricoxib intake to 15.3±8.3 mm/h (p<0.001, VAS resting pain from 48.6±21.4 to 5.2±3.5 mm (p<0.001, swelling (p<0.001 and hyperemia (p< 0.001 indices, and articular index (p<0.001. In 2 patients with baseline uncontrolled arterial hypertension, the drug was discontinued because of elevated blood pressure; periorbital edema was noted in one case by the end of a therapy course. There were no increases in the serum levels of liver enzymes, in the concentrations of creatinine and urea, and in glomerular filtration rate. Conclusion. Etoricoxib (Arcoxia ® is highly effective and safe when used in patients with acute gouty arthritis, including those who had not benefited from previous NSAID

  20. Use of etoricoxib in patients with gout in real clinical practice

    Directory of Open Access Journals (Sweden)

    M S Eliseyev

    2013-06-01

    Full Text Available Objective: to evaluate the efficacy and safety of etoricoxib (Arcoxia ® in gouty patients with an acute arthritis attack in real clinical practice. Subjects and methods. Thirty patients (25 men and 5 women; mean age 52.4±13.5 years with crystal-verified gout participated in the pilot open-label study of the patients with arthritis, including those who had taken other nonsteroidal anti-inflammatory drugs (NSAIDs without any effect. All the patients received etoricoxib (Arcoxia ® in a dose of 120 mg/day for 7 days and, if arthritis persisted, in a dose of 90 mg/day for 7 more days. The authors estimated an articular index, swelling and hyperemia indices, resting and movement pain by a visual analogue scale (VAS, therapy tolerance in the patient's opinion before and 7 days after therapy and, in the patients taking etoricoxib for 14 days, after 14 days of therapy. Biochemical and clinical blood tests were carried out at the first and subsequent visits. Results. Seven days after therapy, an arthritis attack was abolished in 24 of the 28 patients, following 14 days, arthritis persisted only in 1 patient, but the number of affected joints reduced from 8 to 2. Following 7 days, there was a reduction in the mean erythrocyte sedimentation rate from 37.2+10.2 (before etoricoxib intake to 15.3±8.3 mm/h (p<0.001, VAS resting pain from 48.6±21.4 to 5.2±3.5 mm (p<0.001, swelling (p<0.001 and hyperemia (p< 0.001 indices, and articular index (p<0.001. In 2 patients with baseline uncontrolled arterial hypertension, the drug was discontinued because of elevated blood pressure; periorbital edema was noted in one case by the end of a therapy course. There were no increases in the serum levels of liver enzymes, in the concentrations of creatinine and urea, and in glomerular filtration rate. Conclusion. Etoricoxib (Arcoxia ® is highly effective and safe when used in patients with acute gouty arthritis, including those who had not benefited from previous NSAID

  1. The Cerebrospinal Fluid Distribution of Postoperatively Administred Dexketoprofen and Etoricoxib and Their Effect on Pain and Inflammatory Markers in Patients Undergoing Hip Arthroplasty.

    Science.gov (United States)

    Piirainen, Annika; Kokki, Merja; Hautajärvi, Heidi; Lehtonen, Marko; Miettinen, Hannu; Pulkki, Kari; Ranta, Veli-Pekka; Kokki, Hannu

    2016-07-01

    Based on earlier literature, etoricoxib may have a delayed analgesic effect in postoperative setting when analgesic efficacy of nonselective nonsteroidal anti-inflammatory drug dexketoprofen is rapid. This may be caused by slow penetration of etoricoxib into the central nervous system (CNS). Therefore we decided to determine the plasma and cerebrospinal fluid (CSF) pharmacokinetics and pharmacodynamics of dexketoprofen and etoricoxib in patients with hip arthroplasty. A total of 24 patients, scheduled for an elective primary hip arthroplasty were enrolled. After surgery, 12 subjects were randomized to received a single intravenous dose of dexketoprofen, and 12 subjects were given oral etoricoxib. Paired blood and CSF samples were taken up to 24 h for measurement of drug concentrations, interleukin (IL)-6, IL-1ra and blood for interleukin 10. In CSF the highest measured concentration (C max) of dexketoprofen was 4.0 (median) ng/mL (minimum-maximum 1.9-13.9) and time to the highest concentration (t max) 3 h (2-5), and for etoricoxib C max 73 ng/mL (36-127) and t max 5 h (1-24), respectively. Opioid consumption during the first 24 postoperative hours was similar in the two groups. Dexketoprofen and etoricoxib had a similar effect on the postoperative inflammatory response. No significant differences considering pain relief or adverse events were found between the two groups. Dexketoprofen and etoricoxib entered the CNS readily, already at 30 min after administration dexketoprofen was detected in the CSF in most subjects and etoricoxib after 60 min. A single dose of dexketoprofen and etoricoxib provided a similar anti-inflammatory and analgesic response after major orthopaedic surgery.

  2. Extractive Spectrophotometric Methods for the Determination of Etoricoxib in Tablets

    Directory of Open Access Journals (Sweden)

    Kamal Shah

    2009-01-01

    Full Text Available Two simple, rapid, sensitive, precise and economic spectrophotometric methods have been developed for the estimation of etoricoxib in tablet formulation. During the course of study, it was observed that acidic solution of the drug formed colored ion-association complexes with Bromocresol Green (BCG and Bromocresol Purple (BCP which were soluble in chloroform. This property of the drug was followed for the development of colorimetric methods for analysis of drug. The complex of etoricoxib with BCG and BCP showed λmax at 416 nm and 408 nm respectively. These methods were validated statistically. Recovery studies gave satisfactory results indicating that none of common additives and excipients interfere the assay method. The proposed methods are found to be simple, accurate and reproducible that was successfully applied for the analysis of tablet formulation.

  3. Hydrolysis of Ibuprofen Nitrile and Ibuprofen Amide and Deracemisation of Ibuprofen Using Nocardia corallina B-276

    OpenAIRE

    Myrna Solís-Oba; Norberto Manjarrez; Aida Solís; Ricardo Lievano; Herminia Inés Pérez

    2012-01-01

    A novel application of whole cells of Nocardia corallina B-276 for the deracemisation of ibuprofen is reported. This microorganism successfully hydrolysed ibuprofen nitrile to ibuprofen amide, and ibuprofen amide to ibuprofen, using a suspension of cells in a potassium phosphate buffer solution (0.1 M, pH = 7.0). These results can be explained by the presence of NHase and amidase enzymes, but the reactions are not enantioselective and low ee values were obtained. However, (R)-ibuprofen was is...

  4. Seizure following the Use of the COX-2 Inhibitor Etoricoxib

    Directory of Open Access Journals (Sweden)

    Valentina Arnao

    2017-01-01

    Full Text Available We describe a case of epileptic seizures occurring after the use of a COX-2 inhibitor. A 61-year-old man was admitted to our department because of a generalized tonic-clonic seizure. EEG showed generalized slowdown of the activity. Neuroimaging and blood samples studies did not evidence alterations, but a careful pharmacological history revealed that the patient had taken the COX-2 inhibitor etoricoxib to treat lumbago few days before the onset of clinical symptoms. No seizures were reported after etoricoxib discontinuation and an EEG resulted to be normal two months after this. Conclusion. Knowing the pharmacological history of a patient is important for understanding the clinical presentation and selecting appropriate treatment. This is, to the best of our knowledge, the first reported case of generalized seizures associated with the use of COX-2 inhibitors.

  5. Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Jacobsen, Søren; Rasmussen, Jeppe Nørgaard

    2006-01-01

    discharged alive and included in the study; 9773 experienced rehospitalization for MI, and 16 573 died. A total of 5.2% of patients received rofecoxib, 4.3% celecoxib, 17.5% ibuprofen, 10.6% diclofenac, and 12.7% other NSAIDs. For any use of rofecoxib, celecoxib, ibuprofen, diclofenac, and other NSAIDs......, the hazard ratios and 95% confidence intervals for death were 2.80 (2.41 to 3.25; for rofecoxib), 2.57 (2.15 to 3.08; for celecoxib), 1.50 (1.36 to 1.67; for ibuprofen), 2.40 (2.09 to 2.80; for diclofenac), and 1.29 (1.16 to 1.43; for other NSAIDS); there were dose-related increases in risk of death for all...

  6. Pelepasan Ibuprofen Dari Gel Karbomer 940 Kokristal Ibuprofen-Nikotinamida

    OpenAIRE

    Agustin, Rini; Sari, Novica; Zaini, Erizal

    2014-01-01

    Salah satu metode untuk meningkatkan kelarutan adalah co-kristalisasi. Ibuprofen dapat digunakan dalam aplikasi topikal untuk rheumatoid arthrisi, sehingga telah dilakukan sebuah studi tentang formulasi dan pelepasan kokristal ibuprofen-nikotinamida dari gel karbomer 940. Kokristal diperoleh dari metode penguapan pelarut dengan komposisi equimol (1:1). Gel terdiri dari dua formula dengan jumlah ibuprofen yang sama (5%). Formula pertama adalah gel kokristal ibuprofen-nicotinamida dan Formula d...

  7. Reactivity of etoricoxib based on computational study of molecular orbitals, molecular electrostatic potential surface and Mulliken charge analysis

    Science.gov (United States)

    Sachdeva, Ritika; Soni, Abhinav; Singh, V. P.; Saini, G. S. S.

    2018-05-01

    Etoricoxib is one of the selective cyclooxygenase inhibitor drug which plays a significant role in the pharmacological management of arthritis and pain. The theoretical investigation of its reactivity is done using Density Functional Theory calculations. Molecular Electrostatic Potential Surface of etoricoxib and its Mulliken atomic charge distribution are used for the prediction of its electrophilic and nucleophilic sites. The detailed analysis of its frontier molecular orbitals is also done.

  8. Improved Dissolution and Oral Bioavailability of Celecoxib by a Dry Elixir System.

    Science.gov (United States)

    Cho, Kwan Hyung; Jee, Jun-Pil; Yang, Da A; Kim, Sung Tae; Kang, Dongjin; Kim, Dae-Young; Sim, Taeyong; Park, Sang Yeob; Kim, Kyeongsoon; Jang, Dong-Jin

    2018-02-01

    The purpose of this study was to develop and evaluate a dry elixir (DE) system for enhancing the dissolution rate and oral bioavailability of celecoxib. DE system has been used for improving solubility, oral bioavailability of poorly water-soluble drugs. The encapsulated drugs or solubilized drugs in the matrix are rapidly dissolved due to the co-solvent effect, resting in both an enhanced dissolution and bioavailability. DEs containing celecoxib were prepared by spray-drying method and characterized by morphology, drug/ethanol content, drug crystallinity, dissolution rate and oral bioavailability. The ethanol content and drug content in DE system could be easily altered by controlling the spraydrying conditions. The dissolution profile of celecoxib from DE proved to be much higher than that of celecoxib powder due to the nano-structured matrix, amorphous state and encapsulated ethanol. The bioavailability of celecoxib from DEs was compared with celecoxib powder alone and commercial product (Celebrex®) in rats. In particular, blood concentrations of celecoxib form DE formulation were much greater than those of native celecoxib and market product. The data demonstrate that the DE system could provide an useful solid dosage form to enhance the solubility, dissolution rate and oral bioavailability of celecoxib.

  9. Gastric and renal effects of COX-2 selective and non-selective NSAIDs in rats receiving low-dose aspirin therapy

    Directory of Open Access Journals (Sweden)

    Marcella Goetz MORO

    Full Text Available Abstract The consumption of low-dose aspirin (LDA to prevent cardiovascular disease continues to increase worldwide. Consequently, the number of chronic LDA users seeking dental procedures that require complementary acute anti-inflammatory medication has also grown. Considering the lack of literature evaluating this interaction, we analyzed the gastric and renal effects caused by a selective COX-2 inhibitor (etoricoxib and a non-selective COX-2 inhibitor (ibuprofen nonsteroidal anti-inflammatory drug (NSAID in rats receiving chronic LDA therapy. Male Wistar rats were divided into six experimental groups (carboxymethylcellulose (CMC - vehicle; LDA; LDA + ibuprofen; ibuprofen; LDA + etoricoxib; and etoricoxib and submitted to long-term LDA therapy with a subsequent NSAID administration for three days by gavage. After the experimental period, we analyzed gastric and renal tissues and quantified serum creatinine levels. The concomitant use of LDA with either NSAID induced the highest levels of gastric damage when compared to the CMC group (F = 20.26, p 0.05. These results suggest that even the acute use of an NSAID (regardless of COX-2 selectivity can induce gastric damage when combined with the long-term use of low-dose aspirin in an animal model. Additional studies, including clinical assessments, are thus needed to clarify this interaction, and clinicians should be careful of prescribing NSAIDs to patients using LDA.

  10. Ibuprofen overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002655.htm Ibuprofen overdose To use the sharing features on this page, please enable JavaScript. Ibuprofen is a type of nonsteroidal anti-inflammatory drug ( ...

  11. Validated Reverse Phase HPLC Method for the Determination of Impurities in Etoricoxib

    Directory of Open Access Journals (Sweden)

    S. Venugopal

    2011-01-01

    Full Text Available This paper describes the development of reverse phase HPLC method for etoricoxib in the presence of impurities and degradation products generated from the forced degradation studies. The drug substance was subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. The degradation of etoricoxib was observed under base and oxidation environment. The drug was found stable in other stress conditions studied. Successful separation of the drug from the process related impurities and degradation products were achieved on zorbax SB CN (250 x 4.6 mm 5 μm particle size column using reverse phase HPLC method. The isocratic method employed with a mixture of buffer and acetonitrile in a ratio of 60:40 respectively. Disodium hydrogen orthophosphate (0.02 M is used as buffer and pH adjusted to 7.20 with 1 N sodium hydroxide solution. The HPLC method was developed and validated with respect to linearity, accuracy, precision, specificity and ruggedness.

  12. Pre-emptive 8 mg dexamethasone and 120 mg etoricoxib for pain prevention after periodontal surgery: A randomised controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Kranti Konuganti

    2015-01-01

    Full Text Available Several anti-inflammatory drugs have been used to reduce pain and discomfort after periodontal surgeries. This study evaluates the efficacy of using etoricoxib and dexamethasone for pain prevention after open-flap debridement surgery. In this study, 60 patients who were undergoing open flap debridment surgery were randomly assigned to receive a single dose preoperative medication 1 hour prior to surgery. The patients were divided into three groups. In Group 1, 20 patients were given placebo drug orally. In Group 2, 20 patients were given 8 mg Dexamethasone orally and in Group 3, 20 patients were given 120 mg Etoricoxib orally. Patients were instructed to complete a pain diary hourly for the first 8 hours after each surgery and three times a day on the following 3 days. The four point verbal rating scale (VRS 4 and Numerical rate scale were used to assess discomfort. Post-operative Assessment of Pain and Discomfort showed that persistent discomfort and pain were found to be more in the placebo group compared to dexamethasone and etoricoxib group. The adoption of a preemptive medication protocol using either etoricoxib or dexamethasone may be considered effective for pain and discomfort prevention after open-flap debridement surgeries.

  13. Celecoxib inhibits osteoblast maturation by suppressing the expression of Wnt target genes

    Directory of Open Access Journals (Sweden)

    Akihiro Nagano

    2017-01-01

    Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs have been shown to impair bone healing. We previously reported that in colon cancer cells, celecoxib, a COX-2-selective NSAID, inhibited the canonical Wnt/β-catenin signaling pathway. Since this pathway also plays an important role in osteoblast growth and differentiation, we examined the effect of celecoxib on maturation of osteoblast-like cell line MC3T3-E1. Celecoxib induced degradation of transcription factor 7-like 2, a key transcription factor of the canonical Wnt pathway. Subsequently, we analyzed the effect of celecoxib on two osteoblast differentiation markers; runt-related transcription factor 2 (RUNX2 and alkaline phosphatase (ALP, both of which are the products of the canonical Wnt pathway target genes. Celecoxib inhibited the expression of both RUNX2 and ALP by suppressing their promoter activity. Consistent with these observations, celecoxib also strongly inhibited osteoblast-mediated mineralization. These results suggest that celecoxib inhibits osteoblast maturation by suppressing Wnt target genes, and this could be the mechanism that NSAIDs inhibit bone formation and fracture healing.

  14. Ibuprofen dosing for children

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000772.htm Ibuprofen dosing for children To use the sharing features ... much of this medicine can be harmful. How Ibuprofen can Help Your Child Ibuprofen is a type ...

  15. Inhibitory effect of celecoxib on agomelatine metabolism in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    He JY

    2018-03-01

    Full Text Available Jiayang He,1 Ping Fang,2 Xiang Zheng,2 Chenchen Wang,2 Tenghui Liu,2 Bowen Zhang,2 Jian Wen,2 Ren-ai Xu3 1Department of Pharmacy, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China; 2Department of Pharmacology, School of Pharmacy of Wenzhou Medical University, Wenzhou, Zhejiang, China; 3Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China Aim: The aim of this study was to study the effect of celecoxib on agomelatine metabolism in vitro and in vivo. Methods: Ten healthy male Sprague–Dawley rats were randomly divided into 2 groups: Group A (control group and Group B (30 mg/kg celecoxib. Then a single dose of 20 mg/kg agomelatine was administered orally 30 min after administration of celecoxib. In an in vitro study, celecoxib with a series of concentrations was added to an incubation mixture containing recombinant human CYP2C9, human or rat liver microsomes to determine the half-maximal inhibitory concentration on the metabolism of agomelatine. Moreover, a mechanism study was performed to determine the inhibitory effect of celecoxib on CYP2C9. Results: The results showed that a single dose of 30 mg/kg celecoxib significantly increased the area under the concentration-time curve and maximum concentration of agomelatine. In addition, celecoxib inhibited the metabolism of agomelatine in the in vitro studies, which was determined to be by a competitive mechanism on CYP2C9. Those results indicated that celecoxib has an inhibitory effect on the metabolism of agomelatine both in vivo and in vitro. Conclusion: Thus, more attention should be paid when celecoxib is administered combined with agomelatine. Keywords: agomelatine, liver microsomes, pharmacokinetics, celecoxib, CYP2C9

  16. Dual function of tributyrin emulsion: solubilization and enhancement of anticancer effect of celecoxib.

    Science.gov (United States)

    Kang, Sung Nam; Hong, Soon-Seok; Lee, Mi-Kyung; Lim, Soo-Jeong

    2012-05-30

    Tributyrin, a triglyceride analogue of butyrate, can act as a prodrug of an anticancer agent butyrate after being cleaved by intracellular enzymes. We recently demonstrated that the emulsion containing tributyrin as an inner oil phase possesses a potent anticancer activity. Herein we sought to develop tributyrin emulsion as a carrier of celecoxib, a poorly-water soluble drug with anticancer activity. Combined treatment of human HCT116 colon cancer cells with free celecoxib plus tributyrin emulsion inhibited the cellular proliferation more effectively than that of each drug alone, suggesting the possibility of tributyrin emulsion as a potential celecoxib carrier. The mean droplet size of emulsions tended to increase as the tributyrin content in emulsion increases and the concentration of celecoxib loaded in emulsions was affected by tributyrin content and the initial amount of celecoxib, but not by the total amount of surfactant mixture. The concentration of celecoxib required to inhibit the growth of HCT116 and B16-F10 cancer cells by 50% was 2.6- and 3.1-fold lowered by loading celecoxib in tributyrin emulsions, compared with free celecoxib. These data suggest that the anticancer activity of celecoxib was enhanced by loading in tributyrin emulsions, probably due to the solubilization capacity and anticancer activity of tributyrin emulsion. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Effects of celecoxib on proliferation and tenocytic differentiation of tendon-derived stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Kairui; Zhang, Sheng [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Li, Qianqian [Cancer Research Institute, Southern Medical University, Guangzhou 510515 (China); Yang, Jun [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Department of Orthopaedics, 421 Hospital of PLA, Guangzhou 510318 (China); Dong, Weiqiang [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Department of Orthopaedics, The First Affiliated Hospital to Guangzhou Medical University, Guangzhou 510120 (China); Wang, Shengnan; Cheng, Yirong; Al-Qwbani, Mohammed [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Wang, Qiang, E-mail: 1780468505@qq.com [Department of Orthopaedics, Subei People’s Hospital of Jiangsu Province (Clinical Medical College of Yangzhou University), Yangzhou, Jiangsu Province 225001 (China); Yu, Bin, E-mail: carryzhang1985@live.com [Department of Orthopaedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China)

    2014-07-18

    Highlights: • Celecoxib has no effects on TDSCs cell proliferation in various concentrations. • Celecoxib reduced mRNAs levels of tendon associated transcription factor. • Celecoxib reduced mRNAs levels of main tendon associated collagen. • Celecoxib reduced mRNAs levels of tendon associated molecules. - Abstract: NSAIDs are often ingested to reduce the pain and improve regeneration of tendon after tendon injury. Although the effects of NSAIDs in tendon healing have been reported, the data and conclusions are not consistent. Recently, tendon-derived stem cells (TDSCs) have been isolated from tendon tissues and has been suggested involved in tendon repair. Our study aims to determine the effects of COX-2 inhibitor (celecoxib) on the proliferation and tenocytic differentiation of TDSCs. TDSCs were isolated from mice Achilles tendon and exposed to celecoxib. Cell proliferation rate was investigated at various concentrations (0.1, 1, 10 and 100 μg/ml) of celecoxib by using hemocytometer. The mRNA expression of tendon associated transcription factors, tendon associated collagens and tendon associated molecules were determined by reverse transcription-polymerase chain reaction. The protein expression of Collagen I, Collagen III, Scleraxis and Tenomodulin were determined by Western blotting. The results showed that celecoxib has no effects on TDSCs cell proliferation in various concentrations (p > 0.05). The levels of most tendon associated transcription factors, tendon associated collagens and tendon associated molecules genes expression were significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). Collagen I, Collagen III, Scleraxis and Tenomodulin protein expression were also significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). In conclusion, celecoxib inhibits tenocytic differentiation of tendon-derived stem cells but has no effects on cell proliferation.

  18. Effects of celecoxib on proliferation and tenocytic differentiation of tendon-derived stem cells

    International Nuclear Information System (INIS)

    Zhang, Kairui; Zhang, Sheng; Li, Qianqian; Yang, Jun; Dong, Weiqiang; Wang, Shengnan; Cheng, Yirong; Al-Qwbani, Mohammed; Wang, Qiang; Yu, Bin

    2014-01-01

    Highlights: • Celecoxib has no effects on TDSCs cell proliferation in various concentrations. • Celecoxib reduced mRNAs levels of tendon associated transcription factor. • Celecoxib reduced mRNAs levels of main tendon associated collagen. • Celecoxib reduced mRNAs levels of tendon associated molecules. - Abstract: NSAIDs are often ingested to reduce the pain and improve regeneration of tendon after tendon injury. Although the effects of NSAIDs in tendon healing have been reported, the data and conclusions are not consistent. Recently, tendon-derived stem cells (TDSCs) have been isolated from tendon tissues and has been suggested involved in tendon repair. Our study aims to determine the effects of COX-2 inhibitor (celecoxib) on the proliferation and tenocytic differentiation of TDSCs. TDSCs were isolated from mice Achilles tendon and exposed to celecoxib. Cell proliferation rate was investigated at various concentrations (0.1, 1, 10 and 100 μg/ml) of celecoxib by using hemocytometer. The mRNA expression of tendon associated transcription factors, tendon associated collagens and tendon associated molecules were determined by reverse transcription-polymerase chain reaction. The protein expression of Collagen I, Collagen III, Scleraxis and Tenomodulin were determined by Western blotting. The results showed that celecoxib has no effects on TDSCs cell proliferation in various concentrations (p > 0.05). The levels of most tendon associated transcription factors, tendon associated collagens and tendon associated molecules genes expression were significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). Collagen I, Collagen III, Scleraxis and Tenomodulin protein expression were also significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). In conclusion, celecoxib inhibits tenocytic differentiation of tendon-derived stem cells but has no effects on cell proliferation

  19. Eficácia e tolerabilidade da nimesulida versus celecoxib na osteoartrite Efficacy and tolerability of nimesulide versus celecoxib in osteoarthritis

    Directory of Open Access Journals (Sweden)

    Nilzio Antonio da Silva

    2001-03-01

    Full Text Available O objetivo do estudo foi comparar a eficácia e a tolerabilidade da nimesulida versus o celecoxib no tratamento da osteoartrite. A casuística envolveu 57 pacientes com idade entre 40 e 80 anos, que foram randomizados em dois grupos, recebendo as medicações do estudo durante 30 dias de forma simples-cega na dosagem de um comprimido de 100mg de nimesulida duas vezes ao dia e uma cápsula de 100mg de celecoxib duas vezes ao dia. Após a inclusão no estudo na visita basal, foram realizadas três visitas com intervalo de dez dias entre elas. Os aspectos analisados foram: dor em repouso, dor em movimento e dor noturna, através de uma escala analógica da dor, duração da rigidez matinal, capacidade funcional (HAQ, classe funcional ACR-1991 e o índice de gravidade para osteoartrite de joelhos em todas as visitas. Foi também avaliado o tempo para andar 15 metros naqueles pacientes com acometimento de joelhos ou quadril. A avaliação da eficácia e tolerabilidade foi realizada pelo investigador e pelo paciente nas três visitas após o início do tratamento. Os eventos adversos foram registrados durante todo o período do estudo. Houve diminuição significativa e semelhante nas médias da escala para dor ao movimento e dor em repouso para ambos medicamentos em todas as visitas. Houve diminuição da dor noturna ao longo do tratamento no grupo celecoxib e a partir da visita 3 no grupo nimesulida, e ao final do estudo, as médias dos dois grupos foram semelhantes ( p = 0,152. As médias da duração da rigidez matinal diminuíram significativamente no grupo tratado com nimesulida durante todo o seguimento, e no grupo celecoxib a partir da visita 3, sendo semelhantes ao final do estudo ( p= 0,993. O tempo médio para andar 15 metros diminuiu significativamente no grupo nimesulida na visita 4 (p The aim of the present study was to compare the efficacy and tolerability of nimesulide versus celecoxib in the treatment of osteoarthritis. Fifty seven

  20. Celecoxib promotes c-FLIP degradation through Akt-independent inhibition of GSK3.

    Science.gov (United States)

    Chen, Shuzhen; Cao, Wei; Yue, Ping; Hao, Chunhai; Khuri, Fadlo R; Sun, Shi-Yong

    2011-10-01

    Celecoxib is a COX-2 inhibitor that reduces the risk of colon cancer. However, the basis for its cancer chemopreventive activity is not fully understood. In this study, we defined a mechanism of celecoxib action based on degradation of cellular FLICE-inhibitory protein (c-FLIP), a major regulator of the death receptor pathway of apoptosis. c-FLIP protein levels are regulated by ubiquitination and proteasome-mediated degradation. We found that celecoxib controlled c-FLIP ubiquitination through Akt-independent inhibition of glycogen synthase kinase-3 (GSK3), itself a candidate therapeutic target of interest in colon cancer. Celecoxib increased the levels of phosphorylated GSK3, including the α and β forms, even in cell lines, where phosphorylated Akt levels were not increased. Phosphoinositide 3-kinase inhibitors abrogated Akt phosphorylation as expected but had no effect on celecoxib-induced GSK3 phosphorylation. In contrast, protein kinase C (PKC) inhibitors abolished celecoxib-induced GSK3 phosphorylation, implying that celecoxib influenced GSK3 phosphorylation through a mechanism that relied upon PKC and not Akt. GSK3 blockade either by siRNA or kinase inhibitors was sufficient to attenuate c-FLIP levels. Combining celecoxib with GSK3 inhibition enhanced attenuation of c-FLIP and increased apoptosis. Proteasome inhibitor MG132 reversed the effects of GSK3 inhibition and increased c-FLIP ubiquitination, confirming that c-FLIP attenuation was mediated by proteasomal turnover as expected. Our findings reveal a novel mechanism through which the regulatory effects of c-FLIP on death receptor signaling are controlled by GSK3, which celecoxib acts at an upstream level to control independently of Akt.

  1. Celecoxib sensitizes Staphylococcus aureus to antibiotics in macrophages by modulating SIRT1.

    Science.gov (United States)

    Annamanedi, Madhavi; Kalle, Arunasree M

    2014-01-01

    We have previously shown that celecoxib in combination with an antibiotic, increase the bacterial sensitivity to antibiotics. However, the underlying molecular mechanism remained elusive. Efficacy of the combinatorial treatment of celecoxib and ampicillin in vitro was evaluated on macrophage-phagocytosed S. aureus. To elucidate the mechanism, signaling pathway of infection and inflammation involving TLR2, JNK, SIRT1 and NF-κB was studied by FACS, Western blot, ELISA and activity assays. Combinatorial treatment of ampicillin and celecoxib reduced the bacterial load in the macrophages. Further studies clearly suggested the activation of the master regulator of oxidative stress and inflammation SIRT1, by celecoxib when used alone and/or in combination with ampicillin. Also, the results indicated that celecoxib inhibited JNK phosphorylation thereby stabilizing and activating SIRT1 protein that inhibited the COX-2 gene transcription with a significant decrease in the levels of protein inflammatory cytokines like IL-6, MIP-1α and IL-1β via inhibition of NF-κB. SIRT1 activation by celecoxib also resulted in increase of catalase and peroxidase activity with a decrease in Nitric oxide levels. In conclusion, we demonstrate a novel role of celecoxib in controlling inflammation as an enhancer of antibiotic activity against bacteria by modulating SIRT1.

  2. EFFICACY OF PRE-EMPTIVE ETORICOXIB IN PATIENTS UNDERGOING HERNIOPLASTY UNDER GENERAL ANAESTHESIA- A PROSPECTIVE RANDOMISED-CONTROLLED TRIAL

    Directory of Open Access Journals (Sweden)

    Vigil Peter

    2017-02-01

    Full Text Available BACKGROUND Obtaining adequate analgesia in the perioperative period is an enormous task. Studies show that etoricoxib, a selective COX-2 inhibitor given pre-emptively reduces the pain and thereby enhances recovery. The aim of the study is to evaluate the effect of pre-emptive etoricoxib in reducing intraoperative requirements of anaesthetic agents, decreasing postoperative pain and improving functional outcome in patients undergoing inguinal hernioplasty. MATERIALS AND METHODS Two groups, each of thirty patients were formed- Group S and Group C. Group S received a single dose of etoricoxib two hours prior to anaesthesia, while Group C received a placebo. Sevoflurane used during the intraoperative period was calculated. The patient’s pain, sleep and body language in the postoperative period was noted. The rescue analgesics were recorded. Statistical Analysis- The data was analysed using Mann-Whitney U test, Wilcoxon test, independent two sample t-test, Pearson Chi-square test and Fischer’s exact test. Settings and Design- The study was performed in the Department of Anaesthesia in Jubilee Mission Medical College and Regional Institute, Thrissur, from January 2015 to March 2016. This was a prospective study. RESULTS Age, gender and duration of surgery were comparable in both groups. The amount of sevoflurane consumed was less in group S. The postoperative pain was also less in group S at all the time points. Patients in group S demanded less rescue analgesics. 83.3% of the patients in group S had good sleep versus 26.7% in the group C. Up to 93.3% of the patients in group S had a relaxed body language versus 36.7% in group C. No adverse effects were noted. CONCLUSION Pre-emptive etoricoxib is thus a safe, simple and cost-effective therapy in reducing the intraoperative anaesthetic and postoperative analgesic requirements.

  3. 15-Hydroxyprostaglandin dehydrogenase inactivation as a mechanism of resistance to celecoxib chemoprevention of colon tumors.

    LENUS (Irish Health Repository)

    Yan, Min

    2009-06-09

    Pharmacologic inhibitors of the prostaglandin-synthesizing COX-2 oncogene prevent the development of premalignant human colon adenomas. However, resistance to treatment is common. In this study, we show that the adenoma prevention activity of the COX-2 inhibitor celecoxib requires the concomitant presence of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) tumor suppressor gene, and that loss of 15-PGDH expression imparts resistance to celecoxib\\'s anti-tumor effects. We first demonstrate that the adenoma-preventive activity of celecoxib is abrogated in mice genetically lacking 15-PGDH. In FVB mice, celecoxib prevents 85% of azoxymethane-induced tumors >1 mm in size, but is essentially inactive in preventing tumor induction in 15-PGDH-null animals. Indeed, celecoxib treated 15-PGDH null animals develop more tumors than do celecoxib naive WT mice. In parallel with the loss of tumor prevention activity, celecoxib-mediated suppression of colonic PGE(2) levels is also markedly attenuated in 15-PGDH-null versus WT mice. Finally, as predicted by the murine models, humans with low colonic 15-PGDH levels also exhibit celecoxib resistance. Specifically, in a colon adenoma prevention trial, in all cases tested, individuals who developed new adenomas while receiving celecoxib treatment were also found as having low colonic 15-PGDH levels.

  4. Inhibition of HERG potassium channels by celecoxib and its mechanism.

    Directory of Open Access Journals (Sweden)

    Roman V Frolov

    Full Text Available Celecoxib (Celebrex, a widely prescribed selective inhibitor of cyclooxygenase-2, can modulate ion channels independently of cyclooxygenase inhibition. Clinically relevant concentrations of celecoxib can affect ionic currents and alter functioning of neurons and myocytes. In particular, inhibition of Kv2.1 channels by celecoxib leads to arrhythmic beating of Drosophila heart and of rat heart cells in culture. However, the spectrum of ion channels involved in human cardiac excitability differs from that in animal models, including mammalian models, making it difficult to evaluate the relevance of these observations to humans. Our aim was to examine the effects of celecoxib on hERG and other human channels critically involved in regulating human cardiac rhythm, and to explore the mechanisms of any observed effect on the hERG channels.Celecoxib inhibited the hERG, SCN5A, KCNQ1 and KCNQ1/MinK channels expressed in HEK-293 cells with IC(50s of 6.0 µM, 7.5 µM, 3.5 µM and 3.7 µM respectively, and the KCND3/KChiP2 channels expressed in CHO cells with an IC(50 of 10.6 µM. Analysis of celecoxib's effects on hERG channels suggested gating modification as the mechanism of drug action.The above channels play a significant role in drug-induced long QT syndrome (LQTS and short QT syndrome (SQTS. Regulatory guidelines require that all new drugs under development be tested for effects on the hERG channel prior to first administration in humans. Our observations raise the question of celecoxib's potential to induce cardiac arrhythmias or other channel related adverse effects, and make a case for examining such possibilities.

  5. Antidepressant-like effect of celecoxib piroxicam in rat models of depression.

    Science.gov (United States)

    Santiago, Ronise M; Barbiero, Janaína; Martynhak, Bruno J; Boschen, Suelen L; da Silva, Luisa M; Werner, Maria F P; Da Cunha, Claudio; Andreatini, Roberto; Lima, Marcelo M S; Vital, Maria A B F

    2014-06-01

    Beyond the current hypothesis of depression, several new biological substrates have been proposed for this disorder. The present study investigated whether the anti-inflammatory drugs celecoxib and piroxicam have antidepressant activity in animal models of depression. After acute administration, we observed antidepressant-like effects of celecoxib (10 mg/kg) and piroxicam (10 mg/kg) in the modified forced swim test in rats. Piroxicam increased serotonin and norepinephrine levels in the hippocampus. Prolonged (21-day) treatment with celecoxib (10 mg/kg) and piroxicam (10 mg/kg) rescued sucrose preference in a chronic mild stress model of depression. Additionally, the chronic mild stress-induced reduction of hippocampal glutathione was prevented by treatment with celecoxib and piroxicam. Superoxide dismutase in the hippocampus was increased after chronic mild stress compared with the non-stressed saline group. The non-stressed celecoxib and piroxicam groups and stressed piroxicam group exhibited an increase in hippocampal superoxide dismutase activity compared with the stressed saline group. Lipid hydroperoxide was increased in the stressed group treated with vehicle and non-stressed group treated with imipramine but not in the stressed groups treated with celecoxib and piroxicam. These results suggest that the antidepressant-like effects of anti-inflammatory drugs might be attributable to enhanced antioxidant defenses and attenuated oxidative stress in the hippocampus.

  6. Evidence that diclofenac and celecoxib are thyroid hormone receptor beta antagonists.

    Science.gov (United States)

    Zloh, Mire; Perez-Diaz, Noelia; Tang, Leslie; Patel, Pryank; Mackenzie, Louise S

    2016-02-01

    Long term use of NSAIDs is linked to side effects such as gastric bleeding and myocardial infarction. Use of in silico methods and pharmacology to investigate the potential for NSAIDs diclofenac, celecoxib and naproxen to bind to nuclear receptors. In silico screening predicted that both diclofenac and celecoxib has the potential to bind to a number of different nuclear receptors; docking analysis confirmed a theoretical ability for diclofenac and celecoxib but not naproxen to bind to TRβ. Results from TRβ luciferase reporter assays confirmed that both diclofenac and celecoxib display TRβ antagonistic properties; celecoxib, IC50 3.6 × 10(-6)M, and diclofenac IC50 5.3 × 10(-6)M, comparable to the TRβ antagonist MLS (IC50 3.1 × 10(-6)M). In contrast naproxen, a cardio-sparing NSAID, lacked TRβ antagonist effects. In order to determine the effects of NSAIDs in whole organ in vitro, we used isometric wire myography to measure the changes to Triiodothyronine (T3) induced vasodilation of rat mesenteric arteries. Incubation of arteries in the presence of the TRβ antagonist MLS000389544 (10(-5)M), as well as diclofenac (10(-5)M) and celecoxib (10(-5)M) but not naproxen significantly inhibited T3 induced vasodilation compared to controls. These results highlight the benefits of computational chemistry methods used to retrospectively analyse well known drugs for side effects. Using in silico and in vitro methods we have shown that both celecoxib and diclofenac but not naproxen exhibit off-target TRβ antagonist behaviour, which may be linked to their detrimental side effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Ibuprofen: Synthesis, production and properties

    Directory of Open Access Journals (Sweden)

    Mijin Dušan Ž.

    2003-01-01

    Full Text Available Since its introduction in 1969, ibuprofen has become one of the most common painkillers in the world. Ibuprofen in an NSAID (non-steroidal anti-inflammatory drug and like other drugs of its class it possesses analgetic, antipyretic and anti-inflammatory properties. While ibuprofen is a relatively simple molecule, there is still sufficient structural complexity to ensure that a large number of different synthetic approaches are possible. Since the introduction of pharmaceutical products containing ibuprofen, industrial and academic scientists have developed many potential production processes. This paper describes the history, synthesis and production, as well as the properties and stability of ibuprofen.

  8. Celecoxib coupled to dextran via a glutamic acid linker yields a polymeric prodrug suitable for colonic delivery.

    Science.gov (United States)

    Lee, Yonghyun; Kim, Jungyun; Kim, Wooseong; Nam, Joon; Jeong, Seongkeun; Lee, Sunyoung; Yoo, Jin-Wook; Kim, Min-Soo; Jung, Yunjin

    2015-01-01

    Celecoxib, a selective cyclooxygenase-2 inhibitor, is potentially useful for the treatment of colonic diseases such as colorectal cancer and colitis. However, the cardiovascular toxicity of celecoxib limits its routine use in the clinic. Generally, colon-specific delivery of a drug both increases the therapeutic availability in the large intestine and decreases the systemic absorption of the drug, most likely resulting in enhanced therapeutic effects against colonic diseases such as colitis and reduced systemic side effects. To develop a colon-specific prodrug of celecoxib that could reduce its cardiovascular toxicity and improve its therapeutic activity, dextran-glutamic acid-celecoxib conjugate (glutam-1-yl celecoxib-dextran ester [G1CD]) was prepared and evaluated. While stable in pH 1.2 and 6.8 buffer solutions and small-intestinal contents, G1CD efficiently released celecoxib in cecal contents. Oral administration of G1CD to rats delivered a larger amount of celecoxib to the large intestine than free celecoxib. G1CD prevented the systemic absorption of celecoxib and did not decrease the serum level of 6-ketoprostaglandin F1α, an inverse indicator of cardiovascular toxicity of celecoxib. Collectively, G1CD may be a polymeric colon-specific celecoxib prodrug with therapeutic and toxicological advantages.

  9. Synthesis of deuterium labelled ibuprofen

    International Nuclear Information System (INIS)

    Cappon, V.J.; Halstead, G.W.; Theis, D.L.

    1986-01-01

    The preparations of [ar- 2 H 4 ]-ibuprofen and [ar, 3,3,3- 2 H 7 ]-ibuprofen are described. The deuterium was incorporated into the aromatic ring of [ar- 2 H 4 ]-ibuprofen which is a metabolically stable position. [ar, 3,3,3- 2 H 7 ]-ibuprofen was synthesized by the same route using [ 2 H 3 ]-CH 3 I instead of CH 3 I for use as a GC/MS internal standard in stable isotope labelled bioavailability studies. (author)

  10. Longitudinal Numbers-Needed-To-Treat (NNT for Achieving Various Levels of Analgesic Response and Improvement with Etoricoxib, Naproxen, and Placebo in Ankylosing Spondylitis

    Directory of Open Access Journals (Sweden)

    Wang Hongwei

    2011-07-01

    Full Text Available Abstract Background Clinical analgesic trials typically report response as group mean results. However, research has shown that few patients are average and most have responses at the extremes. Moreover, group mean results do not convey response levels and thus have limited value in representing the benefit-risk at an individual level. Responder analyses and numbers-needed-to-treat (NNT are considered more relevant for evaluating treatment response. We evaluated levels of analgesic response and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI score improvement and the associated NNTs. Methods This was a post-hoc analysis of a 6-week, randomized, double-blind study (N = 387 comparing etoricoxib 90 mg, etoricoxib 120 mg, naproxen 1000 mg, and placebo in AS. Spine pain and BASDAI were measured on a 100-mm visual analog scale. The number and percentage of patients achieving ≥30% and ≥50% improvement in both BASDAI and spine pain were calculated and used to determine the corresponding NNTs. Patients who discontinued from the study for any reason were assigned zero improvement beyond 7 days of the time of discontinuation. Results For etoricoxib 90 mg, etoricoxib 120 mg and naproxen 1000 mg, the NNTs at 6 weeks compared with placebo were 2.0, 2.0, and 2.7 respectively for BASDAI ≥30% improvement, and 3.2, 2.8, and 4.1 for ≥50% improvement. For spine pain, the NNTs were 1.9, 2.0, and 3.2, respectively, for ≥30% improvement, and 2.7, 2.5, and 3.7 for ≥50% improvement. The differences between etoricoxib and naproxen exceeded the limit of ±0.5 units described as a clinically meaningful difference for pain. Response rates and NNTs were generally similar and stable over 2, 4, and 6 weeks. Conclusions For every 2 patients treated with etoricoxib, 1 achieved a clinically meaningful (≥30% improvement in spine pain and BASDAI beyond that expected from placebo, whereas the corresponding values were approximately 1 in every 3 patients

  11. Celecoxib use and circulating oxylipins in a colon polyp prevention trial.

    Directory of Open Access Journals (Sweden)

    Jessica A Martinez

    Full Text Available Drugs that inhibit cyclooxygenase (COX-2 and the metabolism of arachidonic acid (ARA to prostaglandin E2 are potent anti-inflammatory agents used widely in the treatment of joint and muscle pain. Despite their benefits, daily use of these drugs has been associated with hypertension, cardiovascular and gastrointestinal toxicities. It is now recognized that ARA is metabolized to a number of bioactive oxygenated lipids (oxylipins by cyclooxygenase (COX, lipoxygenase (LOX, and cytochrome P450 (CYP450 enzymes. Currently, the contribution of individual variability in ARA metabolism in response to the COX-2 inhibitors and potential adverse effects remains poorly understood. Using patient samples from the randomized, placebo-controlled phase III selenium/celecoxib (Sel/Cel trial for the prevention of colorectal adenomatous polyps, we analyzed plasma concentrations of 74 oxylipins in a subset of participants who received celecoxib (n = 90 or placebo (n = 95. We assessed the effect of celecoxib (with and without low dose aspirin on circulating oxylipins and systolic blood pressure (SBP. Individual CYP450- and LOX- but not COX-derived metabolites were higher with celecoxib than placebo (P<0.05 and differences were greater among non-aspirin users. LOX derived 5- and 8-HETE were elevated with celecoxib and positively associated with systolic blood pressure (P = 0.011 and P = 0.019 respectively. 20-HETE, a prohypertensive androgen-sensitive CYP450 metabolite was higher with celecoxib absent aspirin and was positively associated with SBP in men (P = 0.040 but not women. Independent of celecoxib or aspirin, LOX derived metabolites from ARA were strongly associated with SBP including 5- and 8-HETE. These findings support oxylipins, particularly the ARA LOX-derived, in blood pressure control and indicate that pharmacologic inhibition of COX-2 has effects on LOX and CYP450 ARA metabolism that contribute to hypertension in some patients.

  12. Compound list: ibuprofen [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available ibuprofen IBU 00072 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in..._vitro/ibuprofen.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitr...o/ibuprofen.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/...Single/ibuprofen.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive/

  13. Formulation, Characterization, and in Vivo Evaluation of Celecoxib-PVP Solid Dispersion Nanoparticles Using Supercritical Antisolvent Process

    Directory of Open Access Journals (Sweden)

    Eun-Sol Ha

    2014-12-01

    Full Text Available The aim of this study was to develop celecoxib-polyvinylpyrrolidone (PVP solid dispersion nanoparticles with and without surfactant using the supercritical antisolvent (SAS process. The effect of different surfactants such as gelucire 44/14, poloxamer 188, poloxamer 407, Ryoto sugar ester L1695, and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS on nanoparticle formation and dissolution as well as oral absorption of celecoxib-PVP K30 solid dispersion nanoparticles was investigated. Spherical celecoxib solid dispersion nanoparticles less than 300 nm in size were successfully developed using the SAS process. Analysis by differential scanning calorimetry and powder X-ray diffraction showed that celecoxib existed in the amorphous form within the solid dispersion nanoparticles fabricated using the SAS process. The celecoxib-PVP-TPGS solid dispersion nanoparticles significantly enhanced in vitro dissolution and oral absorption of celecoxib relative to that of the unprocessed form. The area under the concentration-time curve (AUC0→24 h and peak plasma concentration (Cmax increased 4.6 and 5.7 times, respectively, with the celecoxib-PVP-TPGS formulation. In addition, in vitro dissolution efficiency was well correlated with in vivo pharmacokinetic parameters. The present study demonstrated that formulation of celecoxib-PVP-TPGS solid dispersion nanoparticles using the SAS process is a highly effective strategy for enhancing the bioavailability of poorly water-soluble celecoxib.

  14. Comparação do efeito analgésico entre etoricoxib 90 mg e dipirona sódica na exérese de pterígio primário com transplante autólogo de conjuntiva Comparison of the analgesic effect between 90 mg etoricoxib and dipyrone after exeresis of primary pterygium with conjunctival autograft

    Directory of Open Access Journals (Sweden)

    Kariza Aiko Frantz

    2009-10-01

    Full Text Available OBJETIVO: Comparar o efeito analgésico entre dipirona sódica e etoricoxib 90 mg após exérese de pterígio primário com transplante autólogo de conjuntiva. MÉTODOS: Trata-se de um ensaio clínico prospectivo, randomizado, duplo-mascarado. Três grupos de 26 pacientes (1 olho por paciente foram operados e receberam as medicações em estudo durante os cinco dias seguintes à cirurgia. Foi utilizada uma escala de dor, numerada de zero a dez, para avaliação pelo paciente no 1É, 3É e 5É dias pós-operatórios. A dor foi classificada em ausente (zero, leve (1 a 3, moderada (4 a 7 e intensa (8 a 10. A análise estatística foi realizada com o software SPSS, versão 11.5. RESULTADOS: Foi observada diferença estatisticamente significativa entre etoricoxib e dipirona no 1É e 3É dia pós-operatório (PO (p=0,001 e p=0,01; respectivamente. O etoricoxib foi superior ao placebo apenas no 1É PO (p=0,04. Não houve diferença de resultados entre dipirona e placebo. CONCLUSÕES: A analgesia do etoricoxib foi superior à do placebo no PO1 e à da dipirona no PO1 e PO3, na exérese de pterígio primário com transplante autólogo de conjuntiva. Não houve diferença significativa da analgesia pós-operatória entre dipirona e placebo no mesmo procedimento.Purpose: To compare the analgesic effect between dipyrone, 90 mg etoricoxib, and placebo after excision of primary pterygium with conjunctival autograft. METHODS: Prospective, randomized, double-masked clinical trial. Three groups of 26 patients (one eye per patient were submitted to surgery and received the study drugs for five days after surgery. A scale of pain was used, graduated from zero to ten, for patient evaluation in the first, third and fifth postoperative days. The pain was classified as absent (zero, mild (1 to 3, moderate (4 to 7 and severe (8 to 10. Statistical analysis was performed with the SPSS, version 11.5. RESULTS: A statistically significant difference was found between

  15. Ibuprofen plus paracetamol versus ibuprofen in acute low back pain: a randomized open label multicenter clinical study.

    Science.gov (United States)

    Ostojic, Predrag; Radunovic, Goran; Lazovic, Milica; Tomanovic-Vujadinovic, Sanja

    2017-01-01

    to estimate whether combination of ibuprofen and paracetamol is more effective than ibuprofen in monotherapy, in the treatment of acute low back pain. 80 adult patients with acute low back pain were randomized into two subgroups. In the first subgroup, 40 patients were treated with ibuprofen 400mg three times a day (TID), whilst patients in the second subgroup (n=40) were treated with a fixed-dose combination tablet of ibuprofen 200mg plus paracetamol 325mg TID, for three consecutive days. Patients were followed for another 7 days. Efficacy and tolerability of both treatment options was assessed. A statistically significant decrease in pain intensity, assessed using a visual analogue scale (pibuprofen monotherapy reported minor gastric intolerability. compared to ibuprofen monotherapy, combination of ibuprofen and paracetamol may provide faster and longer analgesia in patients with acute low back pain, with equally favorable effect on mobility and functional ability and similar tolerability.

  16. Advantages of celecoxib nanosuspension formulation and transformation into tablets.

    Science.gov (United States)

    Dolenc, Andrej; Kristl, Julijana; Baumgartner, Sasa; Planinsek, Odon

    2009-07-06

    Drugs with low aqueous solubility and high permeability (BCS class II) present a high proportion of all drugs. This study examines the critical issues regarding engineering of a nanosuspension tailored to increase drug dissolution rate and its transformation into dry powder suitable for tabletting. Nanosuspensions of celecoxib, a selective COX-2 inhibitor with low water solubility, were produced by the emulsion-diffusion method using three different stabilizers (Tween) 80, PVP K-30 and SDS) and characterized by particle size analysis, dissolution testing, scanning electron microscopy imaging, differential scanning calorimetry and X-ray powder diffraction. Spray-dried nanosuspension was blended with microcrystalline cellulose, and compressed to tablets, and their tensile strength, porosity and elastic recovery of tablets were investigated. The selection of solvent and stabilizers is critical, firstly to achieve controlled crystallization and size, and secondly to increase the wettability of the hydrophobic drug. The crystalline nano-sized celecoxib alone or in tablets showed a dramatic increase of dissolution rate and extent compared to micronized. SEM images showed that the nanoparticle morphology was influenced by the choice of stabilizers. Celecoxib nanosuspension stabilized with PVP K-30 and SDS showed advantages over Tween 80 due to sticking of the dried product and unexpected changes observed on DSC curves. Markedly lower compaction forces are needed for nano-sized compared to micro-sized celecoxib to produce tablets of equal tensile strength.

  17. Downregulation of survivin expression and concomitant induction of apoptosis by celecoxib and its non-cyclooxygenase-2-inhibitory analog, dimethyl-celecoxib (DMC, in tumor cells in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Hofman Florence M

    2006-05-01

    Full Text Available Abstract Background 2,5-Dimethyl-celecoxib (DMC is a close structural analog of the selective cyclooxygenase-2 (COX-2 inhibitor celecoxib (Celebrex® that lacks COX-2-inhibitory function. However, despite its inability to block COX-2 activity, DMC is able to potently mimic the anti-tumor effects of celecoxib in vitro and in vivo, indicating that both of these drugs are able to involve targets other than COX-2 to exert their recognized cytotoxic effects. However, the molecular components that are involved in mediating these drugs' apoptosis-stimulatory consequences are incompletely understood. Results We present evidence that celecoxib and DMC are able to down-regulate the expression of survivin, an anti-apoptotic protein that is highly expressed in tumor cells and known to confer resistance of such cells to anti-cancer treatments. Suppression of survivin is specific to these two drugs, as other coxibs (valdecoxib, rofecoxib or traditional NSAIDs (flurbiprofen, indomethacin, sulindac do not affect survivin expression at similar concentrations. The extent of survivin down-regulation by celecoxib and DMC in different tumor cell lines is somewhat variable, but closely correlates with the degree of drug-induced growth inhibition and apoptosis. When combined with irinotecan, a widely used anticancer drug, celecoxib and DMC greatly enhance the cytotoxic effects of this drug, in keeping with a model that suppression of survivin may be beneficial to sensitize cancer cells to chemotherapy. Remarkably, these effects are not restricted to in vitro conditions, but also take place in tumors from drug-treated animals, where both drugs similarly repress survivin, induce apoptosis, and inhibit tumor growth in vivo. Conclusion In consideration of survivin's recognized role as a custodian of tumor cell survival, our results suggest that celecoxib and DMC might exert their cytotoxic anti-tumor effects at least in part via the down-regulation of survivin – in a

  18. Impact of Chiral Bioanalytical Methods on the Bioequivalence of Ibuprofen Products Containing Ibuprofen Lysinate and Ibuprofen Base.

    Science.gov (United States)

    García-Arieta, Alfredo; Ferrero-Cafiero, Juan Manuel; Puntes, Montse; Gich, Ignasi; Morales-Alcelay, Susana; Tarré, Maite; Font, Xavier; Antonijoan, Rosa Maria

    2016-05-01

    The purpose was to assess the impact of the use of a chiral bioanalytical method on the conclusions of a bioequivalence study that compared two ibuprofen suspensions with different rates of absorption. A comparison of the conclusion of bioequivalence between a chiral method and an achiral approach was made. Plasma concentrations of R-ibuprofen and S-ibuprofen were determined using a chiral bioanalytical method; bioequivalence was tested for R-ibuprofen and for S-ibuprofen separately and for the sum of both enantiomers as an approach for an achiral bioanalytical method. The 90% confidence interval (90% CI) that would have been obtained with an achiral bioanalytical method (90% CI: Cmax: 117.69-134.46; AUC0 (t) : 104.75-114.45) would have precluded the conclusion of bioequivalence. This conclusion cannot be generalized to the active enantiomer (90% CI: Cmax : 103.36-118.38; AUC0 (t) : 96.52-103.12), for which bioequivalence can be concluded, and/or the distomer (90% CI: Cmax : 132.97-151.33; AUC0 (t) : 115.91-135.77) for which a larger difference was observed. Chiral bioanalytical methods should be required when 1) the enantiomers exhibit different pharmacodynamics and 2) the exposure (AUC or Cmax ) ratio of enantiomers is modified by a difference in the rate of absorption. Furthermore, the bioequivalence conclusion should be based on all enantiomers, since the distomer(s) might not be completely inert, in contrast to what is required in the current regulatory guidelines. In those cases where it is unknown if the ratio between enantiomers is modified by changing the rate of absorption, chiral bioanalytical methods should be employed unless enantiomers exhibit the same pharmacodynamics. Chirality 28:429-433, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Antitumor effects of celecoxib in COX-2 expressing and non-expressing canine melanoma cell lines.

    Science.gov (United States)

    Seo, Kyoung-Won; Coh, Ye-Rin; Rebhun, Robert B; Ahn, Jin-Ok; Han, Sei-Myung; Lee, Hee-Woo; Youn, Hwa-Young

    2014-06-01

    Cyclooxygenase-2 (COX-2) is a potential target for chemoprevention and cancer therapy. Celecoxib, a selective COX-2 inhibitor, inhibits cell growth of various types of human cancer including malignant melanoma. In dogs, oral malignant melanoma represents the most common oral tumor and is often a fatal disease. Therefore, there is a desperate need to develop additional therapeutic strategies. The purpose of this study was to investigate the anticancer effects of celecoxib on canine malignant melanoma cell lines that express varying levels of COX-2. Celecoxib induced a significant anti-proliferative effect in both LMeC and CMeC-1 cells. In the CMeC cells, treatment of 50 μM celecoxib caused an increase in cells in the G0/G1 and a decreased proportion of cells in G-2 phase. In the LMeC cells, 50 μM of celecoxib led to an increase in the percentage of cells in the sub-G1 phase and a significant activation of caspase-3 when compared to CMeC-1 cells. In conclusion, these results demonstrate that celecoxib exhibits antitumor effects on canine melanoma LMeC and CMeC-1 cells by induction of G1-S cell cycle arrest and apoptosis. Our data suggest that celecoxib might be effective as a chemotherapeutic agent against canine malignant melanoma. Copyright © 2014. Published by Elsevier Ltd.

  20. IBUPROFEN IN PAIN TREATMENT IN CHILDREN

    Directory of Open Access Journals (Sweden)

    R. V. Denisova

    2012-01-01

    Full Text Available The article contains results of therapeutic efficacy of ibuprofen in pain syndrome management in children. Validity of its use is doubtless. Analgesic effect of Ibuprofen has been confirmed in clinical trials in patients with migraine and ENT-disorders. In this article we also review international experience of ibuprofen use in juvenile arthritis..

  1. The ErbB family and androgen receptor signaling are targets of Celecoxib in prostate cancer.

    Science.gov (United States)

    Brizzolara, Antonella; Benelli, Roberto; Venè, Roberta; Barboro, Paola; Poggi, Alessandro; Tosetti, Francesca; Ferrari, Nicoletta

    2017-08-01

    Inflammation plays a central role in prostate cancer (PCa) development through significant crosstalk between the COX-2-ErbB family receptor network and androgen receptor (AR)-EGFR signaling pathways. The purpose of this work was to determine the ability of the COX-2 inhibitor Celecoxib to modulate the EGFR-AR signaling pathway in androgen-dependent PCa cells and to provide a rationale for its beneficial use in chemopreventive strategies. Functional studies of Celecoxib activity were performed on LNCaP prostate cancer cells. Western blotting, gene expression analysis, dual-luciferase reporter assay and ELISA were applied to assess the Celecoxib mechanisms of action. We found that Celecoxib, through EGF and amphiregulin (AREG) induction, caused EGFR and ErbB2 activation and consequent degradation associated with the inhibition of androgenic signaling. By upregulating the E3 ubiquitin ligase Nrdp1, Celecoxib also efficiently downregulated ErbB3, which is strongly implicated in castration-resistant prostate cancer. Lastly, Celecoxib directly regulated AR transcription and translation independent of ErbB activation by downregulating the RNA binding protein heterogeneous nuclear ribonucleoprotein K (hnRNP K). The simultaneous suppression of ErbB kinases and androgen signaling by Celecoxib represents a novel strategy to interrupt the vicious cycle of AR/ErbB cross-talk with the primary purpose of undermining their resilient signaling in prostate cancer progression. Our data provide important premises for the chemopreventive use of Celecoxib in the clinical management of prostate cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Celecoxib increases miR-222 while deterring aromatase-expressing breast tumor growth in mice

    International Nuclear Information System (INIS)

    Wong, Tsz Yan; Li, Fengjuan; Lin, Shu-mei; Chan, Franky L; Chen, Shiuan; Leung, Lai K

    2014-01-01

    Breast cancer is one of the most deadly diseases in women. Inhibiting the synthesis of estrogen is effective in treating patients with estrogen-responsive breast cancer. Previous studies have demonstrated that use of cyclooxygenase (COX) inhibitors is associated with reduced breast cancer risk. In the present study, we employed an established mouse model for postmenopausal breast cancer to evaluate the potential mechanisms of the COX-2 inhibitor celecoxib. Aromatase-expressing MCF-7 cells were transplanted into ovariectomized athymic mice. The animals were given celecoxib at 1500 ppm or aspirin at 200 ppm by oral administration with androstenedione injection. Our results showed that both COX inhibitors could suppress the cancer xenograft growth without changing the plasma estrogen level. Protein expression of ERα, COX-2, Cyclin A, and Bcl-xL were reduced in celecoxib-treated tumor samples, whereas only Bcl-xL expression was suppressed in those treated with aspirin. Among the breast cancer-related miRNAs, miR-222 expression was elevated in samples treated with celecoxib. Further studies in culture cells verified that the increase in miR-222 expression might contribute to ERα downregulation but not the growth deterrence of cells. Overall, this study suggested that both celecoxib and aspirin could prevent breast cancer growth by regulating proteins in the cell cycle and apoptosis without blocking estrogen synthesis. Besides, celecoxib might affect miR expression in an undesirable fashion

  3. How to Safely Give Ibuprofen

    Science.gov (United States)

    ... of ibuprofen are available in similar forms. How to Give When giving ibuprofen, refer to the following dosage ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

  4. Hydroxyl radical induced degradation of ibuprofen

    Energy Technology Data Exchange (ETDEWEB)

    Illés, Erzsébet, E-mail: erzsebet.illes@chem.u-szeged.hu [Institute of Chemistry, Research Group of Environmental Chemistry, University of Szeged, Szeged (Hungary); Institute of Isotopes, Centre for Energy Research, Hungarian Academy of Sciences, Budapest (Hungary); Takács, Erzsébet [Institute of Isotopes, Centre for Energy Research, Hungarian Academy of Sciences, Budapest (Hungary); Dombi, András [Institute of Chemistry, Research Group of Environmental Chemistry, University of Szeged, Szeged (Hungary); Gajda-Schrantz, Krisztina [Institute of Chemistry, Research Group of Environmental Chemistry, University of Szeged, Szeged (Hungary); Department of Inorganic and Analytical Chemistry, University of Szeged, Szeged (Hungary); EMPA, Laboratory for High Performance Ceramics, Duebendorf (Switzerland); Rácz, Gergely; Gonter, Katalin; Wojnárovits, László [Institute of Isotopes, Centre for Energy Research, Hungarian Academy of Sciences, Budapest (Hungary)

    2013-03-01

    Pulse radiolysis experiments were used to characterize the intermediates formed from ibuprofen during electron beam irradiation in a solution of 0.1 mmol dm{sup −3}. For end product characterization {sup 60}Co γ-irradiation was used and the samples were evaluated either by taking their UV–vis spectra or by HPLC with UV or MS detection. The reactions of {sup ·}OH resulted in hydroxycyclohexadienyl type radical intermediates. The intermediates produced in further reactions hydroxylated the derivatives of ibuprofen as final products. The hydrated electron attacked the carboxyl group. Ibuprofen degradation is more efficient under oxidative conditions than under reductive conditions. The ecotoxicity of the solution was monitored by Daphnia magna standard microbiotest and Vibrio fischeri luminescent bacteria test. The toxic effect of the aerated ibuprofen solution first increased upon irradiation indicating a higher toxicity of the first degradation products, then decreased with increasing absorbed dose. Highlights: ► In hydroxyl radical attack on the ring mainly hydroxylated products form ► The hydrated electron attacks the carboxyl group. ► Oxidative conditions are more effective in ibuprofen decomposition than reductive. ► Ecotoxicity of ibuprofen solution first increases then decreases with irradiation.

  5. Hydroxyl radical induced degradation of ibuprofen

    International Nuclear Information System (INIS)

    Illés, Erzsébet; Takács, Erzsébet; Dombi, András; Gajda-Schrantz, Krisztina; Rácz, Gergely; Gonter, Katalin; Wojnárovits, László

    2013-01-01

    Pulse radiolysis experiments were used to characterize the intermediates formed from ibuprofen during electron beam irradiation in a solution of 0.1 mmol dm −3 . For end product characterization 60 Co γ-irradiation was used and the samples were evaluated either by taking their UV–vis spectra or by HPLC with UV or MS detection. The reactions of · OH resulted in hydroxycyclohexadienyl type radical intermediates. The intermediates produced in further reactions hydroxylated the derivatives of ibuprofen as final products. The hydrated electron attacked the carboxyl group. Ibuprofen degradation is more efficient under oxidative conditions than under reductive conditions. The ecotoxicity of the solution was monitored by Daphnia magna standard microbiotest and Vibrio fischeri luminescent bacteria test. The toxic effect of the aerated ibuprofen solution first increased upon irradiation indicating a higher toxicity of the first degradation products, then decreased with increasing absorbed dose. Highlights: ► In hydroxyl radical attack on the ring mainly hydroxylated products form ► The hydrated electron attacks the carboxyl group. ► Oxidative conditions are more effective in ibuprofen decomposition than reductive. ► Ecotoxicity of ibuprofen solution first increases then decreases with irradiation

  6. Treatment with paracetamol, ketorolac or etoricoxib did not hinder alveolar bone healing: a histometric study in rats

    Directory of Open Access Journals (Sweden)

    Ricardo Nogueira Fracon

    2010-12-01

    Full Text Available Prostaglandins control osteoblastic and osteoclastic function under physiological or pathological conditions and are important modulators of the bone healing process. The non-steroidal anti-inflammatory drugs (NSAIDs inhibit cyclooxygenase (COX activity and consequently prostaglandins synthesis. Experimental and clinical evidence has indicated a risk for reparative bone formation related to the use of non-selective (COX-1 and COX-2 and COX-2 selective NSAIDs. Ketorolac is a non-selective NSAID which, at low doses, has a preferential COX-1 inhibitory effect and etoricoxib is a new selective COX-2 inhibitor. Although literature data have suggested that ketorolac can interfere negatively with long bone fracture healing, there seems to be no study associating etoricoxib with reparative bone formation. Paracetamol/acetaminophen, one of the first choices for pain control in clinical dentistry, has been considered a weak anti-inflammatory drug, although supposedly capable of inhibiting COX-2 activity in inflammatory sites. OBJECTIVE: The purpose of the present study was to investigate whether paracetamol, ketorolac and etoricoxib can hinder alveolar bone formation, taking the filling of rat extraction socket with newly formed bone as experimental model. MATERIAL AND METHODS: The degree of new bone formation inside the alveolar socket was estimated two weeks after tooth extraction by a differential point-counting method, using an optical microscopy with a digital camera for image capture and histometry software. Differences between groups were analyzed by ANOVA after confirming a normal distribution of sample data. RESULTS AND CONCLUSIONS: Histometric results confirmed that none of the tested drugs had a detrimental effect in the volume fraction of bone trabeculae formed inside the alveolar socket.

  7. Randomized comparative trial of efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children

    Directory of Open Access Journals (Sweden)

    Falgun Indravadan Vyas

    2014-01-01

    Full Text Available Objective: Paracetamol and ibuprofen are widely used for fever in children as monotherapy and as combined therapy. None of the treatments is proven clearly superior to others. Hence, the study was planned to compare the efficacy of paracetamol, ibuprofen and paracetamol-ibuprofen combination for treatment of febrile children. Materials and Methods: This was an investigator blind, randomized, comparative, parallel clinical trial conducted in 99 febrile children, 6 months to 12 years of age, allocated to three groups. First group received paracetamol 15 mg/kg, second group received ibuprofen 10 mg/kg and third group received both paracetamol and ibuprofen, all as a single dose by the oral route. Patients were followed-up at intervals of 1, 2, 3 and 4 h post dose by tympanic thermometry. Results: Mean tympanic temperature after 4 h of drug administration was significantly lower in the combination group compared with paracetamol group (P < 0.05; however, the difference was not clinically significant (<1΀C. The rate of fall of temperature was highest in the combination group. Number of afebrile children any time post dose until 4 h was highest in the combination group. Difference between combination and paracetamol was significant for the 1 st h (P = 0.04. Highest fall of temperature was noted in the 1 st h of drug administration in all the groups. No serious adverse events were observed in any of the groups. Conclusion: Paracetamol and ibuprofen combination caused quicker temperature reduction than either paracetamol or ibuprofen alone. If quicker reduction of body temperature is the desired goal of therapy, the use of combination of paracetamol + ibuprofen may be advocated.

  8. Effect of formulation variables on preparation of celecoxib loaded polylactide-co-glycolide nanoparticles.

    Directory of Open Access Journals (Sweden)

    Dustin L Cooper

    Full Text Available Polymer based nanoparticle formulations have been shown to increase drug bioavailability and/or reduce drug adverse effects. Nonsteroidal anti-inflammatory drugs (e.g. celecoxib reduce prostaglandin synthesis and cause side effects such as gastrointestinal and renal complications. The aim of this study was to formulate celecoxib entrapped poly lactide-co-glycolide based nanoparticles through a solvent evaporation process using didodecyldimethylammonium bromide or poly vinyl alcohol as stabilizer. Nanoparticles were characterized for zeta potential, particle size, entrapment efficiency, and morphology. Effects of stabilizer concentration (0.1, 0.25, 0.5, and 1% w/v, drug amount (5, 10, 15, and 20 mg, and emulsifier (lecithin on nanoparticle characterization were examined for formula optimization. The use of 0.1, 0.25, and 0.5% w/v didodecyldimethylammonium bromide resulted in a more than 5-fold increase in zeta potential and a more than 1.5-fold increase in entrapment efficiency with a reduction in particle size over 35%, when compared to stabilizer free formulation. Nanoparticle formulations were also highly influenced by emulsifier and drug amount. Using 0.25% w/v didodecyldimethylammonium bromide NP formulations, peak zeta potential was achieved using 15 mg celecoxib with emulsifier (17.15±0.36 mV and 20 mg celecoxib without emulsifier (25.00±0.18 mV. Peak NP size reduction and entrapment efficiency was achieved using 5 mg celecoxib formulations with (70.87±1.24 nm and 95.55±0.66%, respectively and without (92.97±0.51 nm and 95.93±0.27%, respectively emulsifier. In conclusion, formulations using 5 mg celecoxib with 0.25% w/v didodecyldimethylammonium bromide concentrations produced nanoparticles exhibiting enhanced size reduction and entrapment efficiency. Furthermore, emulsifier free formulations demonstrated improved zeta potential when compared to formulations containing emulsifier (p<0.01. Therefore, our results suggest the use of

  9. Risk management profile of etoricoxib: an example of personalized medicine

    Directory of Open Access Journals (Sweden)

    Paola Patrignani

    2008-08-01

    Full Text Available Paola Patrignani, Stefania Tacconelli, Marta L CaponeDepartment of Medicine and Center of Excellence on Aging, “G. D’Annunzio” University School of Medicine, and “Gabriele D’Annunzio” University Foundation, CeSI, Chieti, ItalyAbstract: The development of nonsteroidal anti-inflammatory drugs (NSAIDs selective for cyclooxygenase (COX-2 (named coxibs has been driven by the aim of reducing the incidence of serious gastrointestinal (GI adverse events associated with the administration of traditional (t NSAIDs – mainly dependent on the inhibition of COX-1 in GI tract and platelets. However, their use has unravelled the important protective role of COX-2 for the cardiovascular (CV system, mainly through the generation of prostacyclin. In a recent nested-case control study, we found that patients taking NSAIDs (both coxibs and tNSAIDs had a 35% increase risk of myocardial infarction. The increased incidence of thrombotic events associated with profound inhibition of COX-2-dependent prostacyclin by coxibs and tNSAIDs can be mitigated, even if not obliterated, by a complete suppression of platelet COX-1 activity. However, most tNSAIDs and coxibs are functional COX-2 selective for the platelet (ie, they cause a profound suppression of COX-2 associated with insufficient inhibition of platelet COX-1 to translate into inhibition of platelet function, which explains their shared CV toxicity. The development of genetic and biochemical markers will help to identify the responders to NSAIDs or who are uniquely susceptible at developing thrombotic or GI events by COX inhibition. We will describe possible strategies to reduce the side effects of etoricoxib by using biochemical markers of COX inhibition, such as whole blood COX-2 and the assessment of prostacyclin biosynthesis in vivo.Keywords: etoricoxib, nonsteroidal antiinflammatory drugs, COX-2, gastrointestinal toxicity, cardiovascular toxicity, prostacyclin

  10. Polyuria, acidosis, and coma following massive ibuprofen ingestion.

    Science.gov (United States)

    Levine, Michael; Khurana, Amandeep; Ruha, Anne-Michelle

    2010-09-01

    Ibuprofen was the first over-the-counter nonsteroidal anti-inflammatory drug available in the United States. Despite being a common agent of ingestion, significant toxicity in overdose is rare. We report a case of a massive ibuprofen ingestion who developed polyuria, acidosis, and coma but survived, despite having a serum ibuprofen concentration greater than previous fatal cases. A 19-year-old man ingested 90 g (1,200 mg/kg) ibuprofen. He was initially awake and alert, but his level of consciousness deteriorated over several hours. Seven hours following the ingestion, he was intubated and mechanically ventilated secondary to loss of airway reflexes. He developed a lactic acidosis and polyuria, which lasted for nearly 24 h. His serum creatinine peaked at 1.12 mg/dL. An ibuprofen level drawn 7 h postingestion was 739.2 mg/L (therapeutic 5-49 mg/L). We describe a case of a massive ibuprofen overdose characterized by metabolic acidosis, coma, and a state of high urine output who survived with aggressive supportive care. This case is unique in several ways. First, ibuprofen levels this high have only rarely been described. Second, polyuria is very poorly described following ibuprofen ingestions.

  11. Perioperative celecoxib administration for pain management after total knee arthroplasty – A randomized, controlled study

    Directory of Open Access Journals (Sweden)

    Lin Wei-Peng

    2008-06-01

    Full Text Available Abstract Background Non-steroidal anti-inflammatory drugs (NSAIDs are recommended for multimodal postoperative pain management. We evaluated opioid-sparing effects and rehabilitative results after perioperative celecoxib administration for total knee arthroplasty. Methods This was a prospective, randomized, observer-blind control study. Eighty patients that underwent total knee arthroplasty were randomized into two groups of 40 each. The study group received a single 400 mg dose of celecoxib, one hour before surgery, and 200 mg of celecoxib every 12 hours for five days, along with patient-controlled analgesic (PCA morphine. The control group received only PCA morphine for postoperative pain management. Visual analog scale (VAS pain scores, active range of motion (ROM, total opioid use and postoperative nausea/vomiting were analyzed. Results Groups were comparable for age, pre-operative ROM, operation duration and intraoperative blood loss. Resting VAS pain scores improved significantly in the celecoxib group, compared with controls, at 48 hrs (2.13 ± 1.68 vs. 3.43 ± 1.50, p = 0.03 and 72 hrs (1.78 ± 1.66 vs. 3.17 ± 2.01, p = 0.02 after surgery. Active ROM also increased significantly in the patients that received celecoxib, especially in the first 72 hrs [40.8° ± 17.3° vs. 25.8° ± 11.5°, p = 0.01 (day 1; 60.7° ± 18.1° vs. 45.0° ± 17.3°, p = 0.004 (day 2; 77.7° ± 15.1° vs. 64.3° ± 16.9°, p = 0.004 (day 3]. Opioid requirements decreased about 40% (p = 0.03 in the celecoxib group. Although patients suffering from post-operative nausea/vomiting decreased from 43% in control group to 28% in celecoxib group, this was not significant (p = 0.57. There were no differences in blood loss (intra- and postoperative between the groups. Celecoxib resulted in no significant increase in the need for blood transfusions. Conclusion Perioperative celecoxib significantly improved postoperative resting pain scores at 48 and 72 hrs, opioid

  12. Ibuprofen plus paracetamol versus ibuprofen in acute low back pain: a randomized open label multicenter clinical study

    Directory of Open Access Journals (Sweden)

    Predrag Ostojic

    2017-01-01

    Full Text Available Objective: to estimate whether combination of ibuprofen and paracetamol is more effective than ibuprofen in monotherapy, in the treatment of acute low back pain. Methods: 80 adult patients with acute low back pain were randomized into two subgroups. In the first subgroup, 40 patients were treated with ibuprofen 400mg three times a day (TID, whilst patients in the second subgroup (n=40 were treated with a fixed-dose combination tablet of ibuprofen 200mg plus paracetamol 325mg TID, for three consecutive days. Patients were followed for another 7 days. Efficacy and tolerability of both treatment options was assessed. Results: A statistically significant decrease in pain intensity, assessed using a visual analogue scale (p

  13. Formulation and Optimization of Celecoxib-Loaded Microspheres ...

    African Journals Online (AJOL)

    factors in the preparation of celecoxib-loaded microspheres. Methods: ... made with biodegradable polymers, are ... filtration on Whatman filter paper no.1 and washed 4 - 5 times with n-hexane [11]. The product was then air-dried at room.

  14. An apple oligogalactan potentiates the growth inhibitory effect of celecoxib on colorectal cancer.

    Science.gov (United States)

    Li, Yuhua; Niu, Yinbo; Sun, Yang; Mei, Lin; Zhang, Bangle; Li, Qian; Liu, Li; Zhang, Rong; Chen, Jianfa; Mei, Qibing

    2014-01-01

    Multiple studies have indicated that selective cyclooxygenase-2 (COX-2) inhibitors possess clinically chemopreventive and preclinically anticancer activities. Their long-term use, however, may be limited by the cardiovascular toxicity. This study tried to investigate whether an apple oligogalactan (AOG) could enhance the growth inhibitory effect of celecoxib on colorectal cancer. Caco-2 and HT-29 cell lines were exposed to different concentrations of AOG (0-1 g/L), celecoxib (0-25 μmol/L), and their combination. COX-2 levels were assessed by reverse transcription PCR and Western blot. COX-2 activity was evaluated by measuring prostaglandin E2 concentration. A colitis-associated colorectal cancer (CACC) mouse model was used to determine the effect of the combination in vivo. AOG (0.1-0.5 g/L) could potentiate the inhibitory effect of physiologic doses of celecoxib (5 μmol/L) on cell growth and decrease COX-2 expressions both at RNA and protein levels. In vivo, the combination (2.5% AOG plus 0.04% celecoxib, w/w) prevented against CACC in mice effectively. Our data indicate that AOG could potentiate the growth inhibitory effect of celecoxib on colorectal cancer both in vitro and in vivo through influencing the expression and function of COX-2 and phosphorylation of MAPKs, which suggests a new possible combinatorial strategy in colorectal cancer therapy.

  15. Celecoxib plus chemoradiotherapy for locally advanced rectal cancer: a phase II TCOG study.

    Science.gov (United States)

    Wang, Ling-Wei; Hsiao, Chin-Fu; Chen, William Tzu-Liang; Lee, Hao-Hsien; Lin, Tzu-Chen; Chen, Hung-Chang; Chen, Hong-Hwa; Chien, Chun-Ru; Lin, Tze-Yi; Liu, Tsang-Wu

    2014-05-01

    To report the results of a phase II trial combining celecoxib and preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Patients with clinical stage II or III rectal cancer were treated with radiotherapy of 44 Gy in 22 fractions. Concurrent chemotherapy consisted of oral tegafur-uracil and folinate on days 1-30 and 38-65. Celecoxib (400 mg/day) given from days 1 to 65. Surgery was done on day 70. The expression of cyclooxygenase 2 (COX-2) in tumor tissues was evaluated microscopically as a prognostic factor. From 2008 to 2011, 53 patients completed CRT+ celecoxib therapy and 47 received radical surgery. Grade 3 diarrhea developed in 5 (9%). Grade 4 anemia was seen in 2 (4%). Pathological complete response (pCR) was seen in 6 (13%). T or N downstaging found in 38 (81%). Sphincter preservation was achieved in 77% of low-positioned tumors. Patients with tumors expressing high-level COX-2 after CRT + celecoxib treatment had inferior pelvic control (P = 0.01), disease-free survival (P = 0.04), and overall survival (P = 0.03) than those with low-level expression. Celecoxib can be safely combined with preoperative CRT for rectal cancer. More intensified adjuvant therapy may be considered for tumors expressing high-level COX-2 after CRT and surgery. © 2013 Wiley Periodicals, Inc.

  16. Synergistic analgesia of duloxetine and celecoxib in the mouse formalin test: a combination analysis.

    Directory of Open Access Journals (Sweden)

    Yong-Hai Sun

    Full Text Available Duloxetine, a serotonin and noradrenaline reuptake inhibitor, and celecoxib, a non-steroidal anti-inflammatory drug, are commonly used analgesics for persistent pain, however with moderate gastrointestinal side effects or analgesia tolerance. One promising analgesic strategy is to give a combined prescription, allowing the maximal or equal efficacy with fewer side effects. In the current study, the efficacy and side effects of combined administration of duloxetine and celecoxib were tested in the mouse formalin pain model. The subcutaneous (s.c. injection of formalin into the left hindpaw induced significant somatic and emotional pain evaluated by the biphasic spontaneous flinching of the injected hindpaw and interphase ultrasonic vocalizations (USVs during the 1 h after formalin injection, respectively. Pretreatment with intraperitoneal (i.p. injection of duloxetine or celecoxib at 1 h before formalin injection induced the dose-dependent inhibition on the second but not first phase pain responses. Combined administration of duloxetine and celecoxib showed significant analgesia for the second phase pain responses. Combination analgesia on the first phase was observed only with higher dose combination. A statistical difference between the theoretical and experimental ED50 for the second phase pain responses was observed, which indicated synergistic interaction of the two drugs. Concerning the emotional pain responses revealed with USVs, we assumed that the antinociceptive effects were almost completely derived from duloxetine, since celecoxib was ineffective when administered alone or reduced the dosage of duloxetine when given in combination. Based on the above findings, acute concomitant administration of duloxetine and celecoxib showed synergism on the somatic pain behavior but not emotional pain behaviors.

  17. Celecoxib suppresses fibroblast growth factor-2 expression in pancreatic ductal adenocarcinoma PANC-1 cells.

    Science.gov (United States)

    Li, Jing; Luo, Miaosha; Wang, Yan; Shang, Boxin; Dong, Lei

    2016-09-01

    The inhibition of cyclooxygenase (COX)-2 has been reported to suppress growth and induce apoptosis in human pancreatic cancer cells. Nevertheless, the precise biological mechanism of how celecoxib, a selective COX-2 inhibitor, regulates the growth and invasion of pancreatic tumors is not completely understood. It has been shown that fibroblast growth factor-2 (FGF-2) and its receptor levels correlate with the inhibition of cancer cell proliferation, migration and invasion in pancreatic ductal adenocarcinoma (PDAC). Therefore, the aim of the present study was to examine the hypothesis that the antitumor activity of celecoxib in PDAC may be exerted through modulation of FGF-2 function. In the present study, we evaluated the effects of celecoxib on the proliferation, migration, invasion and apoptosis of the PANC-1 cell line. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to examine the expression of FGF-2, FGFR-2, ERK1/2 and MMPs. In the present study, FGF-2 and FGFR-2 were expressed in PANC-1 cells and FGF-2 exerted a stimulatory effect on phosphorylated extracellular signal regulated kinase (p-ERK) expression. Celecoxib treatment suppressed FGF-2 and FGFR-2 expression and decreased MMP-2, MMP-9 and p-ERK expression in the PANC-1 cells. Furthermore, celecoxib treatment caused the resistance of PANC-1 cells to FGF-2 induced proliferation, migration and invasion ability, as well as the increase in their apoptotic rate. Our data provide evidence that targeting FGF-2 with celecoxib may be used as an effective treatment in PDAC.

  18. Interaction of celecoxib with different anti-cancer drugs is antagonistic in breast but not in other cancer cells

    International Nuclear Information System (INIS)

    El-Awady, Raafat A.; Saleh, Ekram M.; Ezz, Marwa; Elsayed, Abeer M.

    2011-01-01

    Celecoxib, an inhibitor of cyclooxygenase-2, is being investigated for enhancement of chemotherapy efficacy in cancer clinical trials. This study investigates the ability of cyclooxygenase-2 inhibitors to sensitize cells from different origins to several chemotherapeutic agents. The effect of the drug's mechanism of action and sequence of administration are also investigated. The sensitivity, cell cycle, apoptosis and DNA damage of five different cancer cell lines (HeLa, HCT116, HepG2, MCF7 and U251) to 5-FU, cisplatin, doxorubicin and etoposide ± celecoxib following different incubation schedules were analyzed. We found antagonism between celecoxib and the four drugs in the breast cancer cells MCF7 following all incubation schedules and between celecoxib and doxorubicin in all cell lines except for two combinations in HCT116 cells. Celecoxib with the other three drugs in the remaining four cell lines resulted in variable interactions. Mechanistic investigations revealed that celecoxib exerts different molecular effects in different cells. In some lines, it abrogates the drug-induced G2/M arrest enhancing pre-mature entry into mitosis with damaged DNA thus increasing apoptosis and resulting in synergism. In other cells, it enhances drug-induced G2/M arrest allowing time to repair drug-induced DNA damage before entry into mitosis and decreasing cell death resulting in antagonism. In some synergistic combinations, celecoxib-induced abrogation of G2/M arrest was not associated with apoptosis but permanent arrest in G1 phase. These results, if confirmed in-vivo, indicate that celecoxib is not a suitable chemosensitizer for breast cancer or with doxorubicin for other cancers. Moreover, combination of celecoxib with other drugs should be tailored to the tumor type, drug and administration schedule. - Graphical abstract: Display Omitted Highlights: → Celecoxib may enhance effects of anticancer drugs. → Its combination with four drugs was tested in five cancer cell

  19. Non-steroidal anti-inflammatory drug use is associated with increased risk of out-of-hospital cardiac arrest

    DEFF Research Database (Denmark)

    Sondergaard, Kathrine B; Weeke, Peter; Wissenberg, Mads

    2017-01-01

    Arrest Registry, all persons with OHCA during 2001-10 were identified. NSAID use 30 days before OHCA was categorized as follows: diclofenac, naproxen, ibuprofen, rofecoxib, celecoxib, and other. Risk of OHCA associated with use of NSAIDs was analysed by conditional logistic regression in case......-time-control models matching four controls on sex and age per case to account for variation in drug utilization over time. We identified 28 947 persons with OHCA of whom 3376 were treated with an NSAID up to 30 days before OHCA. Ibuprofen and diclofenac were the most commonly used NSAIDs and represented 51.0% and 21.......8% of total NSAID use, respectively. Use of diclofenac (odds ratio [OR], 1.50 [95% confidence interval (CI) 1.23-1.82]) and ibuprofen [OR, 1.31 (95% CI 1.14-1.51)] was associated with a significantly increased risk of OHCA. Use of naproxen [OR, 1.29 (95% CI 0.77-2.16)], celecoxib [OR, 1.13 (95% CI 0...

  20. Ursodeoxycholic acid counteracts celecoxib in reduction of duodenal polyps in patients with familial adenomatous polyposis: a multicentre, randomized controlled trial

    Science.gov (United States)

    2013-01-01

    Background Due to prophylactic colectomy, mortality in patients with familial adenomatous polyposis (FAP) has changed, with duodenal cancer currently being the main cause of death. Although celecoxib reduces duodenal polyp density in patients with FAP, its long-term use may increase the risk of cardiovascular events and alternatives need to be explored. Preclinical studies suggest that the combination of celecoxib with ursodeoxycholic acid (UDCA) is a potentially effective strategy. We performed a randomized, double-blind, placebo-controlled trial to investigate the effect of celecoxib and UDCA co-treatment on duodenal adenomatosis in patients with FAP. Methods Patients with FAP received celecoxib (400 mg twice daily) and UDCA (1000-2000 mg daily, ~20-30 mg/kg/day, n=19) or celecoxib and placebo (n=18) orally for 6 months. Primary outcome was drug efficacy, assessed by comparing duodenal polyp density at pre- and post-intervention by blinded review of endoscopic recordings. As secondary outcomes, cell proliferation, apoptosis, and COX-2 levels in normal duodenal mucosa were assessed by immunohistochemistry or real-time quantitative polymerase chain reaction. Results In intention-to-treat analysis, deceased polyp density was observed after celecoxib/placebo treatment (p=0.029), whereas increased polyp density was observed after celecoxib/UDCA treatment (p=0.014). The difference in change in duodenal polyp density was statistically significant between the groups (p=0.011). No changes in secondary outcomes were observed. Thirty patients (81%) reported one or more adverse events, 16 patients (84%, Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE) grade 1–3) treated with celecoxib/UDCA and 14 patients (78%, CTCAE grade 1–2) treated with celecoxib/placebo. Nine patients (24%) discontinued intervention prematurely, 5 patients (26%) treated with celecoxib/UDCA and 4 patients (22%) treated with celecoxib/placebo. Conclusions Celecoxib reduces duodenal

  1. Celecoxib accelerates functional recovery after sciatic nerve crush in the rat

    Directory of Open Access Journals (Sweden)

    Fernández-Garza Nancy E

    2008-11-01

    Full Text Available Abstract The inflammatory response appears to be essential in the modulation of the degeneration and regeneration process after peripheral nerve injury. In injured nerves, cyclooxygenase-2 (COX-2 is strongly upregulated around the injury site, possibly playing a role in the regulation of the inflammatory response. In this study we investigated the effect of celecoxib, a COX-2 inhibitor, on functional recovery after sciatic nerve crush in rats. Unilateral sciatic nerve crush injury was performed on 10 male Wistar rats. Animals on the experimental group (n = 5 received celecoxib (10 mg/kg ip immediately before the crush injury and daily for 7 days after the injury. Control group (n = 5 received normal saline at equal regimen. A sham group (n = 5, where sciatic nerve was exposed but not crushed, was also evaluated. Functional recovery was then assessed by calculating the sciatic functional index (SFI on days 0,1,7,14 and 21 in all groups, and registering the day of motor and walking onset. In comparison with control group, celecoxib treatment (experimental group had significant beneficial effects on SFI, with a significantly better score on day 7. Anti-inflammatory drug celecoxib should be considered in the treatment of peripheral nerve injuries, but further studies are needed to explain the mechanism of its neuroprotective effects.

  2. Effects of Cetuximab Combined with Celecoxib on Apoptosis and KDR and AQP1 
Expression in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Honggang XIA

    2013-12-01

    Full Text Available Background and objective Neoadjuvant chemotherapy is a new development in the treatment of lung cancer. In recent years, cetuximab and celecoxib have been commonly used in this procedure. This study aims to explore the effect of cetuximab combined with celecoxib on apoptosis and KDR and AQP1 expression in lung cancer A549 cells. Method The cells were cultured in RPMI-1640 and then divided into four groups: control group, 1 nmol/L cetuximab group, 25 µmol/L celecoxib group, and 1 nmol/L cetuximab+25 µmol/L celecoxib group. The treatment time was 48 h. The mRNA and protein expression levels of KDR and AQP1 were detected by RT-PCR and Western blot, respectively. The apoptosis, proliferation, and invasive ability of A549 cells before and after transfection were examined using flow cytometry, MTT, and transwell methods. Results Cetuximab and celecoxib inhibited the growth of A549 cells in a dose-dependent manner. Their combination produced a greater growth inhibition than when either was used alone (P<0.01. Cetuximab and celecoxib both induced the apoptosis of A549 cells, and their combination produced a higher apoptosis rate (P<0.01. Cetuximab in combination with celecoxib also induced G1 phase arrest and downregulated the expression of KDR and AQP1 in A549 cells (P<0.05. As a result, the invasion ability of the A549 cells was significantly decreased. Conclusion Cetuximab in combination with celecoxib can synergistically inhibit the growth of A549 cells and downregulate the expression of KDR and AQP1 in A549 cells. The combination of cetuximab and celecoxib is a potential strategy for lung cancer therapy.

  3. Inhibition of bacterial multidrug resistance by celecoxib, a cyclooxygenase-2 inhibitor.

    Science.gov (United States)

    Kalle, Arunasree M; Rizvi, Arshad

    2011-01-01

    Multidrug resistance (MDR) is a major problem in the treatment of infectious diseases and cancer. Accumulating evidence suggests that the cyclooxygenase-2 (COX-2)-specific inhibitor celecoxib would not only inhibit COX-2 but also help in the reversal of drug resistance in cancers by inhibiting the MDR1 efflux pump. Here, we demonstrate that celecoxib increases the sensitivity of bacteria to the antibiotics ampicillin, kanamycin, chloramphenicol, and ciprofloxacin by accumulating the drugs inside the cell, thus reversing MDR in bacteria.

  4. Análisis coste-efectividad del empleo de celecoxib en el tratamiento de la artrosis Cost-effectiveness analysis of the use of celecoxib for the treatment of osteoarthritis

    Directory of Open Access Journals (Sweden)

    A. Moreno

    2003-02-01

    Full Text Available Antecedentes: Los antiinflamatorios no esteroideos (AINE, utilizados en el tratamiento de la artrosis, pueden producir reacciones adversas gastrointestinales (GI graves. Celecoxib, un inhibidor específico de la ciclooxigenasa 2 (COX-2, ha demostrado una eficacia equivalente a los AINE convencionales con un mejor perfil de tolerabilidad y seguridad. Objetivo: La finalidad de este estudio ha sido realizar un análisis coste-efectividad sobre el uso de celecoxib frente a los AINE clásicos en el tratamiento de la artrosis. Material y métodos: El análisis coste-efectividad se ha diseñado mediante un modelo farmacoeconómico, definiéndose como unidad de efectividad a cada año de vida ganado tras la toma de celecoxib o AINE. La probabilidad de que aparezcan los diferentes resultados clínicos se ha obtenido de artículos publicados y de asunciones incorporadas. Sólo se han valorado los costes directos médicos (medicación, hospitalización, pruebas complementarias, analíticas, visitas extras, etc., sin haberse incluido otros costes. La perspectiva del estudio ha sido la del Sistema Nacional de Salud y el horizonte temporal elegido ha sido de 6 meses. Resultados: El coste adicional por cada año de vida ganado secundario al uso de celecoxib frente a los AINE clásicos asciende a 8.017 € (1.333.834 ptas.. El análisis de sensibilidad muestra cómo estos valores son sensibles a la modificación del coste de AINE y gastroprotector, así como a la inclusión de grupos poblacionales con edades más bajas. Conclusiones: Celecoxib puede ser considerado como una opción coste-efectiva en el tratamiento de la artrosis, ya que va a evitar muertes y a ganar años de vida para los pacientes con un coste adicional razonable y moderado, cuando se compara con los AINE. Su eficiencia aumenta a medida que se utiliza en poblaciones con menor edad media y, probablemente, en aquellas con mayor riesgo de desarrollar complicaciones GI.Background: Non

  5. Synthesis, Docking and Biological Activities of Novel Hybrids Celecoxib and Anthraquinone Analogs as Potent Cytotoxic Agents

    Science.gov (United States)

    Almutairi, Maha S.; Hegazy, Gehan H.; Haiba, Mogedda E.; Ali, Hamed I.; Khalifa, Nagy M.; Soliman, Abd El-mohsen M.

    2014-01-01

    Herein, novel hybrid compounds of celecoxib and 2-aminoanthraquinone derivatives have been synthesized using condensation reactions of celecoxib with 2-aminoanthraquinone derivatives or 2-aminoanthraquinon with celecoxib derivatives. Celecoxib was reacted with different acid chlorides, 2-chloroethylisocyanate and bis (2-chloroethyl) amine hydrochloride. These intermediates were then reacted with 2-aminoanthraquinone. Also the same different acid chlorides and 2-chloroethylisocyanate were reacted with 2-aminoanthraquinone and the resulting intermediates were reacted with celecoxib to give isomers for the previous compounds. The antitumor activities against hepatic carcinoma tumor cell line (HEPG2) have been investigated in vitro, and all these compounds showed promising activities, especially compound 3c, 7, and 12. Flexible docking studies involving AutoDock 4.2 was investigated to identify the potential binding affinities and the mode of interaction of the hybrid compounds into two protein tyrosine kinases namely, SRC (Pp60v-src) and platelet-derived growth factor receptor, PDGFR (c-Kit). The compounds in this study have a preferential affinity for the c-Kit PDGFR PTK over the non-receptor tyrosine kinase SRC (Pp60v-src). PMID:25490139

  6. Analgesic efficacy with rapidly absorbed ibuprofen sodium dihydrate in postsurgical dental pain

    DEFF Research Database (Denmark)

    Nørholt, Sven Erik; Hallmer, F; Hartlev, Jens

    2011-01-01

    To evaluate the onset of analgesic effect for a new formulation of ibuprofen sodium dihydrate versus conventional ibuprofen (ibuprofen acid).......To evaluate the onset of analgesic effect for a new formulation of ibuprofen sodium dihydrate versus conventional ibuprofen (ibuprofen acid)....

  7. Radiological Evaluation of the effects of varied doses of Celecoxib on fracture healing in dogs

    Directory of Open Access Journals (Sweden)

    Edwin Aihanuwa Uwagie-Ero and Rapheal Chukwujekwu Kene

    2011-04-01

    Full Text Available To determine if Cyclooxygenase -2 (COX-2 functions in fracture healing, 10 dogs were treated with COX-2-selective nonsteroidal anti-inflammatory drugs (Celecoxib to reduce and stop COX-2-dependent prostaglandin production. Radiographic testing evaluation determined that fracture healing was not affected in dogs treated with a low dose of COX-2-selective NSAIDs (celecoxib and delayed union was observed in dogs treated with a high dose of COX-2-selective NSAIDs (celecoxib. Celecoxib dose of 5 mg/kg/day did not affect fracture callus formed in the study group and did not cause a significant increase in the proportion of delayed unions, however, at a dose of 10 mg/kg/day it reduced the rate of fracture callus formation and significantly increased the proportion of delayed unions for dogs in the group. [Veterinary World 2011; 4(2.000: 75-76

  8. Celecoxib induces proliferation and Amphiregulin production in colon subepithelial myofibroblasts, activating erk1-2 signaling in synergy with EGFR.

    Science.gov (United States)

    Benelli, Roberto; Venè, Roberta; Minghelli, Simona; Carlone, Sebastiano; Gatteschi, Beatrice; Ferrari, Nicoletta

    2013-01-01

    The COX-2 inhibitor Celecoxib, tested in phase III trials for the prevention of sporadic colon adenomas, reduced the appearance of new adenomas, but was unable to affect the incidence of colon cancer. Moreover the 5years follow-up showed that patients discontinuing Celecoxib treatment had an increased incidence of adenomas as compared to the placebo arm. In the APC(min/+) mouse model short term treatment with Celecoxib reduced gut adenomas, but a prolonged administration of the drug induced fibroblast activation and intestinal fibrosis with a final tumor burden. The way Celecoxib could directly activate human colon myofibroblasts (MF) has not yet been investigated. We found that MF are activated by non toxic doses of Celecoxib. Celecoxib induces erk1-2 and Akt phosphorylation within 5'. This short term activation is apparently insufficient to cause phenotypic changes, but the contemporary triggering of EGFR causes an impressive synergic effect inducing MF proliferation and the neo-expression and release of Amphiregulin (AREG), a well known EGFR agonist involved in colon cancer progression. As a confirm to these observations, the erk inhibitor U0126 and the EGFR inhibitors Tyrphostin and Cetuximab were able to contrast AREG induction. Our data provide evidence that Celecoxib directly activates MF empowering EGFR signaling. According to these results the association with EGFR (or erk1-2) inhibitors could abolish the off-target activity of Celecoxib, possibly extending the potential of this drug for colon cancer prevention. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Celecoxib plays a multiple role to peripheral blood lymphocytes and allografts in acute rejection in rats after cardiac transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xue-feng; ZHANG Fan; LIU Hong-yu; SUN Guo-dong; LIU Zong-hong; L(U) Hang; CHI Chao; LI Chun-yu

    2009-01-01

    Background Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a non-steroidal anti-inflammatory drug used as an adjuvant to sensitize cancer cells to apoptosis. However, in rats suffering from acute rejection, celecoxib reduced apoptosis of myocardial cells. We hypothesize that celecoxib reduces myocardial apoptosis either by inducing apoptosis in peripheral blood lymphocytes (PBLs) or by altering the percentage of CD4+ and CD8+ lymphocytes. Methods After cardiac transplantation, rats were administered intragastrically with celecoxib (50 mg/kg per day) for 3, 5 or 7 days, at which time the graft was excised and evaluated for organ rejection. In addition, PBLs were isolated from the blood to determine PBLs apoptosis, and the percentage of CD4+ and CD8+ lymphocytes. Results Celecoxib induced PBLs apoptosis in 3 days, but protected the cells from apoptosis at 5 and 7 days. Also, the percentage of CD4+ lymphocytes decreased only at 3 days, but a reduction in the percentage of CD8+ lymphocytes was not seen until 7 days after the transplant surgery. Celecoxib only decreased acute rejection at 5 days, with no discernible difference in rejection after 3 and 7 days. Conclusions The results suggested that celecoxib displayed a multiple physiological function in a time-dependent manner.

  10. Estudo da interferência de diferentes dietas nutricionais sobre as ações antiinflamatória e analgésica do Etoricoxib (Arcóxia®)

    OpenAIRE

    Bianchetti, érica Silva

    2006-01-01

    O etoricoxib (Arcóxia®) um medicamento novo posicionado para liderar a próxima geração de inibidores seletivos de COX-2 é um coxib de segunda geração potente e de ação rápida sendo motivo atualmente de muitos ensaios clínicos É o mais seletivo de COX-2 de todos os coxibs O objetivo deste estudo foi estudar em modelos in vivo a interferência sobre a atividade antiinflamatória e analgésica do etoricoxib antiinflamatório inibidor seletivo de COX-2 associado a diferentes tipos de dietas nutricion...

  11. Synthesis, Docking and Biological Activities of Novel Hybrids Celecoxib and Anthraquinone Analogs as Potent Cytotoxic Agents

    Directory of Open Access Journals (Sweden)

    Maha S. Almutairi

    2014-12-01

    Full Text Available Herein, novel hybrid compounds of celecoxib and 2-aminoanthraquinone derivatives have been synthesized using condensation reactions of celecoxib with 2-aminoanthraquinone derivatives or 2-aminoanthraquinon with celecoxib derivatives. Celecoxib was reacted with different acid chlorides, 2-chloroethylisocyanate and bis (2-chloroethyl amine hydrochloride. These intermediates were then reacted with 2-aminoanthraquinone. Also the same different acid chlorides and 2-chloroethylisocyanate were reacted with 2-aminoanthraquinone and the resulting intermediates were reacted with celecoxib to give isomers for the previous compounds. The antitumor activities against hepatic carcinoma tumor cell line (HEPG2 have been investigated in vitro, and all these compounds showed promising activities, especially compound 3c, 7, and 12. Flexible docking studies involving AutoDock 4.2 was investigated to identify the potential binding affinities and the mode of interaction of the hybrid compounds into two protein tyrosine kinases namely, SRC (Pp60v-src and platelet-derived growth factor receptor, PDGFR (c-Kit. The compounds in this study have a preferential affinity for the c-Kit PDGFR PTK over the non-receptor tyrosine kinase SRC (Pp60v-src.

  12. Detection and Analysis of the Quality of Ibuprofen Granules

    Science.gov (United States)

    Yu-bin, Ji; Xin, LI; Guo-song, Xin; Qin-bing, Xue

    2017-12-01

    The Ibuprofen Granules comprehensive quality testing to ensure that it is in accordance with the provisions of Chinese pharmacopoeia. With reference of Chinese pharmacopoeia, the Ibuprofen Granules is tested by UV, HPLC, in terms of grain size checking, volume deviation, weight loss on drying detection, dissolution rate detection, and quality evaluation. Results indicated that Ibuprofen Granules conform to the standards. The Ibuprofen Granules are qualified and should be permitted to be marketed.

  13. Serum ibuprofen levels of extremely preterm infants treated prophylactically with oral ibuprofen to prevent patent ductus arteriosus

    NARCIS (Netherlands)

    Kanmaz, Gozde; Erdeve, Omer; Canpolat, Fuat Emre; Oguz, Serife Suna; Uras, Nurdan; Altug, Nahide; Greijdanus, Ben; Dilmen, Ugur

    The aim of this study was to explore the effects of early oral ibuprofen administration on the incidence of hemodynamically significant patent ductus arteriosus (hsPDA) and define the association between serum ibuprofen levels and ductal closure. Preterm infants with a gestational age of <28 weeks

  14. Immune activation and HIV-specific T cell responses are modulated by a cyclooxygenase-2 inhibitor in untreated HIV-infected individuals: An exploratory clinical trial.

    Directory of Open Access Journals (Sweden)

    Christian Prebensen

    Full Text Available Pathologically elevated immune activation and inflammation contribute to HIV disease progression and immunodeficiency, potentially mediated by elevated levels of prostaglandin E2, which suppress HIV-specific T cell responses. We have previously shown that a high dose of the cyclooxygenase-2 inhibitor celecoxib can reduce HIV-associated immune activation and improve IgG responses to T cell-dependent vaccines. In this follow-up study, we included 56 HIV-infected adults, 28 antiretroviral therapy (ART-naïve and 28 on ART with undetectable plasma viremia but CD4 counts below 500 cells/μL. Patients in each of the two study groups were randomized to receive 90 mg qd of the cyclooxygenase-2 inhibitor etoricoxib for six months, two weeks or to a control arm, respectively. T cell activation status, HIV Gag-specific T cell responses and plasma inflammatory markers, tryptophan metabolism and thrombin generation were analyzed at baseline and after four months. In addition, patients received tetanus toxoid, conjugated pneumococcal and seasonal influenza vaccines, to which IgG responses were determined after four weeks. In ART-naïve patients, etoricoxib reduced the density of the activation marker CD38 in multiple CD8+ T cell subsets, improved Gag-specific T cell responses, and reduced in vitro plasma thrombin generation, while no effects were seen on plasma markers of inflammation or tryptophan metabolism. No significant immunological effects of etoricoxib were observed in ART-treated patients. Patients receiving long-term etoricoxib treatment had poorer tetanus toxoid and conjugated pneumococcal vaccine responses than those receiving short-course etoricoxib. Cyclooxygenase-2 inhibitors may attenuate harmful immune activation in HIV-infected patients without access to ART.

  15. Ibuprofen regulation of microtubule dynamics in cystic fibrosis epithelial cells.

    Science.gov (United States)

    Rymut, Sharon M; Kampman, Claire M; Corey, Deborah A; Endres, Tori; Cotton, Calvin U; Kelley, Thomas J

    2016-08-01

    High-dose ibuprofen, an effective anti-inflammatory therapy for the treatment of cystic fibrosis (CF), has been shown to preserve lung function in a pediatric population. Despite its efficacy, few patients receive ibuprofen treatment due to potential renal and gastrointestinal toxicity. The mechanism of ibuprofen efficacy is also unclear. We have previously demonstrated that CF microtubules are slower to reform after depolymerization compared with respective wild-type controls. Slower microtubule dynamics in CF cells are responsible for impaired intracellular transport and are related to inflammatory signaling. Here, it is identified that high-dose ibuprofen treatment in both CF cell models and primary CF nasal epithelial cells restores microtubule reformation rates to wild-type levels, as well as induce extension of microtubules to the cell periphery. Ibuprofen treatment also restores microtubule-dependent intracellular transport monitored by measuring intracellular cholesterol transport. These effects are specific to ibuprofen as other cyclooxygenase inhibitors have no effect on these measures. Effects of ibuprofen are mimicked by stimulation of AMPK and blocked by the AMPK inhibitor compound C. We conclude that high-dose ibuprofen treatment enhances microtubule formation in CF cells likely through an AMPK-related pathway. These findings define a potential mechanism to explain the efficacy of ibuprofen therapy in CF. Copyright © 2016 the American Physiological Society.

  16. The enhancement of radiosensitivity by celecoxib, selective cyclooxygenase-2 inhibitor, on human cancer cells expressing differential levels of cyclooxygenase-2

    International Nuclear Information System (INIS)

    Pyo, Hong Ryull; Shin, You Keun; Kim, Hyun Seok; Seong, Jin Sil; Suh, Chang Ok; Kim, Gwi Eon

    2003-01-01

    To investigate the modulation of radiosensitivity by celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on cancer cells over- and under-expressing COX-2. A clonogenic radiation survival analysis was performed on A549 human lung and MCF-7 human breast cancer cell lines incubated in both 1 and 10% fetal bovine serum (FBS) containing media. The apoptosis in both cell lines was measured after treatment with radiation and/or celecoxib. Celecoxib enhanced the radiation sensitivity of the A549 cells in the medium containing the 10% FBS, with radiation enhancement ratios of 1.58 and 1.81 respectively, at surviving fractions of 0.1, with 30 μ M and 50 μ M celecoxib. This enhanced radiosensitivity disappeared in the medium containing the 1% FBS. Celecoxib did not change the radiation sensitivity of the MCF-7 cells in either media. The induction of apoptosis by celecoxib and radiation was not synergistic in either cell line. Celecoxib, a selective COX-2 inhibitor, preferentially enhanced the effect of radiation on COX-2 over-expressing cancer cells compared to the cells with a low expression, and this effect disappeared on incubation of the cells during drug treatment in the medium with suboptimal serum concentration. Apoptosis did not appear to be the underlying mechanism of this radiation enhancement effect due to celecoxib on the A549 cells. These findings suggest radiosensitization by a selective COX-2 inhibitor is COX-2 dependent

  17. Encapsulation of Ibuprofen in CD-MOF and Related Bioavailability Studies.

    Science.gov (United States)

    Hartlieb, Karel J; Ferris, Daniel P; Holcroft, James M; Kandela, Irawati; Stern, Charlotte L; Nassar, Majed S; Botros, Youssry Y; Stoddart, J Fraser

    2017-05-01

    Although ibuprofen is one of the most widely used nonsteroidal anti-inflammatory drugs (NSAIDs), it exhibits poor solubility in aqueous and physiological environments as a free acid. In order to improve its oral bioavailability and rate of uptake, extensive research into the development of new formulations of ibuprofen has been undertaken, including the use of excipients as well as ibuprofen salts, such as ibuprofen lysinate and ibuprofen, sodium salt. The ultimate goals of these studies are to reduce the time required for maximum uptake of ibuprofen, as this period of time is directly proportional to the rate of onset of analgesic/anti-inflammatory effects, and to increase the half-life of the drug within the body; that is, the duration of action of the effects of the drug. Herein, we present a pharmaceutical cocrystal of ibuprofen and the biocompatible metal-organic framework called CD-MOF. This metal-organic framework (MOF) is based upon γ-cyclodextrin (γ-CD) tori that are coordinated to alkali metal cations (e.g., K + ions) on both their primary and secondary faces in an alternating manner to form a porous framework built up from (γ-CD) 6 cubes. We show that ibuprofen can be incorporated within CD-MOF-1 either by (i) a crystallization process using the potassium salt of ibuprofen as the alkali cation source for production of the MOF or by (ii) absorption and deprotonation of the free-acid, leading to an uptake of 23-26 wt % of ibuprofen within the CD-MOF. In vitro viability studies revealed that the CD-MOF is inherently not affecting the viability of the cells with no IC 50 value determined up to a concentration of 100 μM. Bioavailability investigations were conducted on mice, and the ibuprofen/CD-MOF pharmaceutical cocrystal was compared to control samples of the potassium salt of ibuprofen in the presence and absence of γ-CD. From these animal studies, we observed that the ibuprofen/CD-MOF-1 cocrystal exhibits the same rapid uptake of ibuprofen as the

  18. Ibuprofen: from invention to an OTC therapeutic mainstay.

    Science.gov (United States)

    Rainsford, K D

    2013-01-01

    The discovery of ibuprofen's anti-inflammatory activity by Dr (now Professor) Stewart Adams and colleagues (Boots Pure Chemical Company Ltd, Nottingham, UK) 50 years ago represented a milestone in the development of anti-inflammatory analgesics. Subsequent clinical studies were the basis for ibuprofen being widely accepted for treating painful conditions at high anti-rheumatic doses (≤ 2400 mg/d), with lower doses (≤ 1200 mg/d for ≤ 10 days) for mild-moderate acute pain (e.g. dental pain, headache, dysmenorrhoea, respiratory symptoms and acute injury). The early observations have since been verified in studies comparing ibuprofen with newer cyclo-oxygenase-2 selective inhibitors ('coxibs'), paracetamol and other non-steroidal anti-inflammatory drugs (NSAIDs). The use of the low-dose, non-prescription, over-the-counter (OTC) drug was based on marketing approval in 1983 (UK) and 1984 (USA); and it is now available in over 80 countries. The relative safety of OTC ibuprofen has been supported by large-scale controlled studies. It has the same low gastro-intestinal (GI) effects as paracetamol (acetaminophen) and fewer GI effects than aspirin. Ibuprofen is a racemate. Its physicochemical properties and the short plasma-elimination half-life of the R(-) isomer, together with its limited ability to inhibit cyclo-oxygenase-1 (COX-1) and thus prostaglandin (PG) synthesis, compared with that of S(+)-ibuprofen, are responsible for the relatively low GI toxicity. The R(-) isomer is then converted in the body to the S(+) isomer after absorption in the GI tract. Ex vivo inhibition of COX-1 (thromboxane A(2)) and COX-2 (PGE(2)) at the plasma concentrations of S(+)-ibuprofen corresponding to those found in the plasma following ingestion of 400 mg ibuprofen in dental and other inflammatory pain models provides evidence of the anti-inflammatory mechanism at OTC dosages. R(-)-ibuprofen has effects on leucocytes, suggesting that ibuprofen has anti-leucocyte effects, which

  19. An economic model of long-term use of celecoxib in patients with osteoarthritis

    Directory of Open Access Journals (Sweden)

    Rublee Dale

    2007-07-01

    Full Text Available Abstract Background Previous evaluations of the cost-effectiveness of the cyclooxygenase-2 selective inhibitor celecoxib (Celebrex, Pfizer Inc, USA have produced conflicting results. The recent controversy over the cardiovascular (CV risks of rofecoxib and other coxibs has renewed interest in the economic profile of celecoxib, the only coxib now available in the United States. The objective of our study was to evaluate the long-term cost-effectiveness of celecoxib compared with nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs in a population of 60-year-old osteoarthritis (OA patients with average risks of upper gastrointestinal (UGI complications who require chronic daily NSAID therapy. Methods We used decision analysis based on data from the literature to evaluate cost-effectiveness from a modified societal perspective over patients' lifetimes, with outcomes expressed as incremental costs per quality-adjusted life-year (QALY gained. Sensitivity tests were performed to evaluate the impacts of advancing age, CV thromboembolic event risk, different analytic horizons and alternate treatment strategies after UGI adverse events. Results Our main findings were: 1 the base model incremental cost-effectiveness ratio (ICER for celecoxib versus nsNSAIDs was $31,097 per QALY; 2 the ICER per QALY was $19,309 for a model in which UGI ulcer and ulcer complication event risks increased with advancing age; 3 the ICER per QALY was $17,120 in sensitivity analyses combining serious CV thromboembolic event (myocardial infarction, stroke, CV death risks with base model assumptions. Conclusion Our model suggests that chronic celecoxib is cost-effective versus nsNSAIDs in a population of 60-year-old OA patients with average risks of UGI events.

  20. Modeling the onset and offset of dental pain relief by ibuprofen.

    Science.gov (United States)

    Li, Hanbin; Mandema, Jaap; Wada, Russell; Jayawardena, Shyamalie; Desjardins, Paul; Doyle, Geraldine; Kellstein, David

    2012-01-01

    Onset and offset of dental pain relief by ibuprofen following third molar extraction were modeled in a randomized, double-blind, placebo-controlled, parallel-group, 8-hour study of patients receiving either a novel effervescent ibuprofen tablet (400 mg; N = 30), standard ibuprofen tablets (Nurofen(®) 2 × 200 mg; N = 22), or placebo (N = 37). An Emax model was fit to pain relief scores. Linear hazard models were used to analyze the time to first perceptible relief (TFPR), the time to meaningful pain relief (TMPR), and time to remedication (REMD). Nomograms were created to correlate TFPR, TMPR, and REMD with different ibuprofen pharmacokinetic profiles. Effervescent ibuprofen was absorbed rapidly with 95% completion within 15 minutes. Maximum pain relief score by ibuprofen was 1.8 units greater than placebo, with an EC50 (effect-site) for ibuprofen concentration of 10.2 µg·mL(-1). The likelihood to achieve TFPR and TMPR was doubled for every 10 µg·mL(-1) increase in ibuprofen plasma concentration. REMD risk decreased 40-fold as the categorical pain relief score increased from 0 to 3. Rapid absorption of ibuprofen effervescent resulted in an earlier TFPR and TMPR, and a lower REMD rate than standard ibuprofen. The nomograms may be useful in predicting the onset and offset of new faster acting ibuprofen formulations, based on pharmacokinetic profiles.

  1. Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats.

    Science.gov (United States)

    Gao, Jin-Hang; Wen, Shi-Lei; Feng, Shi; Yang, Wen-Juan; Lu, Yao-Yao; Tong, Huan; Liu, Rui; Tang, Shi-Hang; Huang, Zhi-Yin; Tang, Ying-Mei; Yang, Jin-Hui; Xie, Hui-Qi; Tang, Cheng-Wei

    2016-10-01

    Abnormal angiogenesis is critical for portal hypertension in cirrhosis. Except for etiological treatment, no efficient medication or regime has been explored to treat the early stage of cirrhosis when angiogenesis is initiated or overwhelming. In this study, we explored an anti-angiogenesis effort through non-cytotoxic drugs octreotide and celecoxib to treat early stage of cirrhotic portal hypertension in an animal model. Peritoneal injection of thioacetamide (TAA) was employed to induce liver cirrhosis in rats. A combination treatment of celecoxib and octreotide was found to relieve liver fibrosis, portal venous pressure, micro-hepatic arterioportal fistulas, intrahepatic and splanchnic angiogenesis. Celecoxib and octreotide exerted their anti-angiogenesis effect via an axis of cyclooxygenase-2/prostaglandin E2/EP-2/somatostatin receptor-2, which consequently down-regulated phosphorylation of extracellular signal-regulated kinase (p-ERK)-hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) integrated signaling pathways. In conclusions, combination of celecoxib and octreotide synergistically ameliorated liver fibrosis and portal hypertension of the cirrhotic rats induced by TAA via the inhibition of intrahepatic and extrahepatic angiogenesis. The potential mechanisms behind the regimen may due to the inactivation of p-ERK-HIF-1α-VEGF signaling pathway.

  2. Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain.

    Science.gov (United States)

    Derry, Christopher J; Derry, Sheena; Moore, R Andrew

    2013-06-24

    Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Some combinations of ibuprofen and paracetamol are available for use without prescription in some acute pain situations. To assess the efficacy and adverse effects of single dose oral ibuprofen plus paracetamol for acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4 of 12, 2013), MEDLINE (1950 to May 21st 2013), EMBASE (1974 to May 21st 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. Randomised, double-blind clinical trials of single dose, oral ibuprofen plus paracetamol compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used validated equations to calculate the area under the pain relief versus time curve and derive the proportion of participants with at least 50% of maximum pain relief over six hours. We calculated relative risk (RR) and number needed to treat to benefit (NNT) for ibuprofen plus paracetamol, ibuprofen alone, or placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events. Searches identified three studies involving 1647 participants. Each of them examined several dose combinations. Included studies provided data from 508 participants for the comparison of ibuprofen 200 mg + paracetamol 500 mg with placebo, 543

  3. Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Jin-Hang Gao

    Full Text Available BACKGROUND: Increased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2 in the cirrhotic liver might be a potential target to ameliorate portal hypertension. OBJECTIVE: To verify the effect of celecoxib, a selective inhibitor of COX-2, on portal hypertension and the mechanisms behind it. METHODS: Cirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA. 36 rats were randomly assigned to control, TAA and TAA+celecoxib groups. Portal pressures were measured by introduction of catheters into portal vein. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and mRNAs for collagen III and α-SMA. The neovasculature was determined by hepatic vascular areas, vascular casts and CD31 expression. Expressions of COX-2, vascular endothelial growth factor (VEGF, VEGF receptor-2 (VEGFR-2 and related signal molecules were quantitated. RESULTS: Compared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8%, p<0.01. Celecoxib treatment greatly reduced the tortuous hepatic portal venules. The data of fibrotic areas, CD31expression, mRNA levels of α-SMA and collagen III in TAA+celecoxib group were much lower than those in TAA group, p<0.01. Furthermore, the up-regulation of hepatic mRNA and protein levels of VEGF, VEGFR-2 and COX-2 induced by TAA was significantly inhibited after celecoxib treatment. The expressions of prostaglandin E2 (PGE2, phosphorylated extracellular signal-regulated kinase (p-ERK, hypoxia-inducible factor-1α (HIF-1α, and c-fos were also down-regulated after celecoxib treatment. CONCLUSIONS: Long term administration of celecoxib can efficiently ameliorate portal hypertension in TAA rat model by its dual inhibitory effects on the intrahepatic fibrosis and angiogenesis. The anti-angiogenesis effect afforded by celecoxib may attribute to its

  4. Dissolution of ibuprofen enantiomers from coprecipitates and suspensions containing chiral excipients.

    Science.gov (United States)

    Janjikhel, R K; Adeyeye, C M

    1999-01-01

    The purpose of this research was to evaluate the stereospecific interaction of ibuprofen with chiral excipients such as hydroxypropyl-beta-cyclodextrin (HPCD), tartaric acid, sucrose, hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), and a nonchiral excipient, citric acid. Coprecipitates of ibuprofen were prepared in molar ratios ranging between 1:0.5 and 1:10 by a solvent evaporation method and characterized using x-ray diffraction, Fourier-transform infrared (FTIR) spectroscopy, and dissolution testing. Phase solubility studies of ibuprofen were carried out by adding excess amount of ibuprofen to aqueous excipient solutions of varying concentrations. Interaction was studied in suspensions of ibuprofen with HPMC, MC, and sucrose stored at room temperature and 60 degrees C for 12 weeks. Solubility of ibuprofen in HPCD solutions increased 10-fold, whereas solubility decreased in the tartaric and citric acid solutions, a result of decreased pH with increased amount of the acids in which ibuprofen (pKa 4.8) is less soluble. Phase solubility diagrams of ibuprofen in aqueous HPCD, citric acid, and tartaric acid solutions showed no stereospecific differences in solubility of the two enantiomers. X-ray diffraction studies showed that ibuprofen exists in a crystalline form at low ibuprofen-to-excipient ratios, whereas at the higher ratios, it exists in an amorphous form. FTIR spectroscopy for HPCD coprecipitates showed a shift of the carbonyl stretching band of ibuprofen to a higher wavelength with a markedly decreased intensity, probably because of a breakdown in the intermolecular hydrogen bonding with ibuprofen and restriction of the drug molecule in the HPCD cavity, respectively. Dissolution profiles of the coprecipitates demonstrated higher dissolution rates than those of pure ibuprofen. The presence of chiral excipients did not appear to cause stereoselective release of the drug from the coprecipitates and the suspensions.

  5. Overexpression of p65 attenuates celecoxib-induced cell death in MDA-MB-231 human breast cancer cell line

    Directory of Open Access Journals (Sweden)

    Wang Ling

    2013-02-01

    Full Text Available Abstract Background Celecoxib is a selective cyclooxygenase (COX-2 inhibitor that has been reported to reduce the risk of breast cancer. In our previous study, celecoxib induced apoptosis and caused cell cycle arrest at the G0/G1 phase in the breast cancer cell line MDA-MB-231, and its effects were mediated by downregulation of NF-κB signaling. The NF-κB p65/RelA subunit may play a role in cell death through the activation of anti-apoptotic target genes including the inhibitor of apoptosis (IAP and Bcl-2 families, and inhibition of protein kinase B/Akt. The aim of the present study was to investigate p65 as the potential target of celecoxib treatment and determine whether p65 overexpression can override the inhibitory effect of celecoxib on NF-κB activity and affect cell survival. Methods The effects of p65 overexpression on celecoxib-inhibited NF-κB transcriptional activity were examined by western blotting, electrophoretic mobility shift assay (EMSA and luciferase reporter gene assay. Cell viability and cell death were evaluated by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazoliumbromide (MTT assay, and the levels of cleaved poly(ADP-ribose polymerase (PARP and caspase. Anti-apoptotic NF-κB target genes and cell cycle regulators were examined by western blotting to screen for the expression of target genes under direct regulation by p65. Results Overexpression of p65 increased NF-κB transcriptional activity and interfered with celecoxib-mediated apoptosis as assessed by MTT assay and caspase-3, caspase-9, and PARP expressions. Exogenously overexpressed p65 upregulated NF-κB-responsive genes, including anti-apoptotic genes such as survivin and XIAP, and the cell cycle regulatory gene cyclin D1. However, p65 overexpression did not affect celecoxib-induced p-Akt inactivation, suggesting that celecoxib might have separate molecular mechanisms for regulating Akt signaling independently of its inhibition of NF-κB transcriptional

  6. Celecoxib ameliorates portal hypertension of the cirrhotic rats through the dual inhibitory effects on the intrahepatic fibrosis and angiogenesis.

    Science.gov (United States)

    Gao, Jin-Hang; Wen, Shi-Lei; Yang, Wen-Juan; Lu, Yao-Yao; Tong, Huan; Huang, Zhi-Yin; Liu, Zhang-Xu; Tang, Cheng-Wei

    2013-01-01

    Increased intra-hepatic resistance to portal blood flow is the primary factor leading to portal hypertension in cirrhosis. Up-regulated expression of cyclooxygenase-2 (COX-2) in the cirrhotic liver might be a potential target to ameliorate portal hypertension. To verify the effect of celecoxib, a selective inhibitor of COX-2, on portal hypertension and the mechanisms behind it. Cirrhotic liver model of rat was established by peritoneal injection of thiacetamide (TAA). 36 rats were randomly assigned to control, TAA and TAA+celecoxib groups. Portal pressures were measured by introduction of catheters into portal vein. Hepatic fibrosis was assessed by the visible hepatic fibrotic areas and mRNAs for collagen III and α-SMA. The neovasculature was determined by hepatic vascular areas, vascular casts and CD31 expression. Expressions of COX-2, vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2) and related signal molecules were quantitated. Compared with TAA group, the portal pressure in TAA+celecoxib group was significantly decreased by 17.8%, pportal venules. The data of fibrotic areas, CD31expression, mRNA levels of α-SMA and collagen III in TAA+celecoxib group were much lower than those in TAA group, pprotein levels of VEGF, VEGFR-2 and COX-2 induced by TAA was significantly inhibited after celecoxib treatment. The expressions of prostaglandin E2 (PGE2), phosphorylated extracellular signal-regulated kinase (p-ERK), hypoxia-inducible factor-1α (HIF-1α), and c-fos were also down-regulated after celecoxib treatment. Long term administration of celecoxib can efficiently ameliorate portal hypertension in TAA rat model by its dual inhibitory effects on the intrahepatic fibrosis and angiogenesis. The anti-angiogenesis effect afforded by celecoxib may attribute to its modulation on VEGF/VEGFR-2 through the down-regulation of integrated signal pathways involving PGE2- HIF-1α- VEGF and p-ERK- c-fos- VEGFR-2.

  7. Celecoxib treatment does not alter recruitment and activation of osteoclasts in the initial phase of experimental tooth movement

    Directory of Open Access Journals (Sweden)

    E.P. Carvalho-Filho

    2012-10-01

    Full Text Available In a previous study, we reported that the short-term treatment with celecoxib, a non-steroidal anti-inflammatory drug (NSAID attenuates the activation of brain structures related to nociception and does not interfere with orthodontic incisor separation in rats. The conclusion was that celecoxib could possibly be prescribed for pain in orthodontic patients. However, we did not analyze the effects of this drug in periodontium. The aim of this follow-up study was to analyze effects of celecoxib treatment on recruitment and activation of osteoclasts and alveolar bone resorption after inserting an activated orthodontic appliance between the incisors in our rat model. Twenty rats (400-420 g were pretreated through oral gavage with celecoxib (50 mg/kg or vehicle (carboxymethylcellulose 0.4%. After 30 min, they received an activated (30 g orthodontic appliance, set not to cause any palate disjunction. In sham animals, the appliance was immediately removed after introduction. All animals received ground food and, every 12 h, celecoxib or vehicle. After 48 h, they were anesthetized and transcardiacally perfused through the aorta with 4% formaldehyde. Subsequently, maxillae were removed, post-fixed and processed for histomorphometry or immunohistochemical analyses. As expected, incisor distalization induced an inflammatory response with certain histological changes, including an increase in the number of active osteoclasts at the compression side in group treated with vehicle (appliance: 32.2±2.49 vs sham: 4.8 ± 1.79, P<0.05 and celecoxib (appliance: 31.0±1.45 vs sham: 4.6±1.82, P<0.05. The treatment with celecoxib did not modify substantially the histological alterations and the number of active osteoclasts after activation of orthodontic appliance. Moreover, we did not see any difference between the groups with respect to percentage of bone resorption area. Taken together with our previous results we conclude that short-term treatment with celecoxib

  8. Celecoxib treatment does not alter recruitment and activation of osteoclasts in the initial phase of experimental tooth movement

    Science.gov (United States)

    Carvalho-Filho, E.P.; Stabile, A.C.; Ervolino, E.; Stuani, M.B.S.; Iyomasa, M.M.; Rocha, M.J.A.

    2012-01-01

    In a previous study, we reported that the short-term treatment with celecoxib, a non-steroidal anti-inflammatory drug (NSAID) attenuates the activation of brain structures related to nociception and does not interfere with orthodontic incisor separation in rats. The conclusion was that celecoxib could possibly be prescribed for pain in orthodontic patients. However, we did not analyze the effects of this drug in periodontium. The aim of this follow-up study was to analyze effects of celecoxib treatment on recruitment and activation of osteoclasts and alveolar bone resorption after inserting an activated orthodontic appliance between the incisors in our rat model. Twenty rats (400–420 g) were pretreated through oral gavage with celecoxib (50 mg/kg) or vehicle (carboxymethyl-cellulose 0.4%). After 30 min, they received an activated (30 g) orthodontic appliance, set not to cause any palate disjunction. In sham animals, the appliance was immediately removed after introduction. All animals received ground food and, every 12 h, celecoxib or vehicle. After 48 h, they were anesthetized and transcardiacally perfused through the aorta with 4% formaldehyde. Subsequently, maxillae were removed, post-fixed and processed for histomorphometry or immunohistochemical analyses. As expected, incisor distalization induced an inflammatory response with certain histological changes, including an increase in the number of active osteoclasts at the compression side in group treated with vehicle (appliance:32.2±2.49 vs sham: 4.8±1.79, P<0.05) and celecoxib (appliance: 31.0±1.45 vs sham: 4.6±1.82, P<0.05). The treatment with celecoxib did not modify substantially the histological alterations and the number of active osteoclasts after activation of orthodontic appliance. Moreover, we did not see any difference between the groups with respect to percentage of bone resorption area. Taken together with our previous results we conclude that short-term treatment with celecoxib can indeed be

  9. In vitro and in vivo therapeutic activity of ibuprofen against dermatophytes

    International Nuclear Information System (INIS)

    AlJanabi, Ali S

    2009-01-01

    To evaluate the in vitro and in vivo therapeutic activity of ibuprofen against dermatophytes. The period of study ranged from June to September 2008. For in vitro investigation of ibuprofen activity, measurement of colony diameter, and dry weight were employed against 4 isolated strains of dermatophytes from 46 patients (30-43 years) suffering from dermatophytoses at Morgan Hospital, Hilla City, Iraq in June 2008. For the in vivo evaluation of ibuprofen, rabbits as the main subjects, were infected with dermatophytes and treated with prepared ibuprofen cream (15mg/gm). In vitro application of ibuprofen showed cidal activity on 4 strains of dermatophytes at minimum inhibitory concentrations of 200 ug/ml. The infected rabbits were successfully cured of dermatophytoses after treatment with ibuprofen cream. Based on in vitro and in vivo application, Ibuprofen can be used as a short-term cure for dermatophytoses. (author)

  10. [Plasma ibuprofen enantiomers and their pharmacokinetics in Beagle dogs determined by HPLC].

    Science.gov (United States)

    Wang, Hong-yan; Kong, Ai-ying; Yang, Bo; Yan, Liang-ping; Di, Xin

    2015-12-01

    A chiral high-performance liquid chromatography method was developed for the simultaneous determination of ibuprofen enantiomers in dog plasma. It was used to study the pharmacokinetics in the Beagle dog after intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen. Ketoprofen was chosen as the internal standard. After a simple precipitation using methanol as the precipitating solvent, both analytes and IS were separated on a Kromasil 100-5CHI-TBB chiral column (250 mm x4.6 mm, 5 μm) with isocratic elution using acetonitrile - 20 mmol x L(-1) phosphate buffer (pH 3.0, containing 5% methanol) (6 : 4) as the mobile phase. The detection wavelength was 220 nm. Liner calibration curves for both of the ibuprofen enantiomers were over the concentration range from 0.5 to 50 μg x mL(-1) with a lower limit of quantification of 0.5 μg x mL(-1), the accuracies were all in standard ranges. The intra- and inter- assay precisions were all below 7%. The recovery rate was 93.1% to 100.4%. The experiments proved that the method was simple, rapid and sensitive. It can be used in the quantitative determination of ibuprofen enantiomers in dog plasma. The method was used to determine the concentration of ibuprofen enantiomers in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen (9 mg x kg(-1)) and the pharmacokinetics parameters were calculated based on the concentration-time curves. The C(max) of S-ibuprofen in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen were 30.8 ± 4.7, 46.1 ± 5.9 and 20.0 ± 2.6 μg x mL(-1), respectively. In terms of the exposure of active ingredient, it revealed a significant difference between the administration of S-ibuprofen and the other two groups. The systematical R- to S- chiral inversion was discussed. Comparing the pharmacokinetic parameters at different doses, chiral inversion were 70.1% ± 36.6% and 76

  11. A novel NSAID derivative, phospho-ibuprofen, prevents AOM-induced colon cancer in rats

    Science.gov (United States)

    OUYANG, NENGTAI; JI, PING; WILLIAMS, JENNIE L.

    2013-01-01

    The cancer chemopreventive properties and gastrointestinal toxicity of ibuprofen are well documented. Modification of existing NSAIDs has improved on the chemopreventive efficacy of this agent and reduced its toxicity. In this study, ibuprofen and a modified derivative (phospho-modified ibuprofen or p-ibuprofen) were used in a chemically induced model of colon cancer. Fisher 344 rats were injected with azoxymethane then treated with either ibuprofen (500 ppm) or p-ibuprofen (900 ppm) for 20 weeks to observe aberrant crypt foci (ACF) or 40 weeks to evaluate tumor incidence and multiplicity. β-catenin and p65 were measured in colonic tissues by immunofluorescence staining. Equal molar doses of ibuprofen (75 and 670 mg/kg) and p-ibuprofen (135 and 1,215 mg/kg) were administered to rats for 7 days to assess acute toxicity. The in vitro effect of p-ibuprofen on COX-2 and PGE2 synthesis, β-catenin expression and NF-κB activity were examined in RAW 264.7 macrophage and HCT 116 colon cancer cells. At week 20, p-ibuprofen and ibuprofen significantly reduced the multiplicity of ACF compared with control (pibuprofen and ibuprofen reduced the multiplicity of colon tumors compared with control (pibuprofen (670 mg/kg) and p-ibuprofen (1,215 mg/kg) resulted in stomach ulceration in 85.7% (6 out of 7) and 14.3% (1 out of 7) of rats, respectively, with pibuprofen and p-ibuprofen suppressed β-catenin nuclear translocation in colon cancer cells. In addition, p-ibuprofen but not ibuprofen inhibited NF-κB activation in colon cancer cells. Collectively, these results suggest that p-ibuprofen is a potential effective novel drug for long-term use in colon cancer prevention. PMID:23291777

  12. A review of dexketoprofen trometamol in acute pain.

    Science.gov (United States)

    Hanna, Magdi; Moon, Jee Y

    2018-03-23

    Dexketoprofen trometamol is a modified non-selective COX inhibitor with a rapid onset of action that is available as both oral and parenteral formulations. The aim of this narrative review was to assess the efficacy and tolerability/safety of dexketoprofen trometamol in acute pain states using the best available published scientific evidence (randomized controlled clinical trials and systematic reviews/meta-analyses). Literature retrieval was performed via Medline, Embase and the Cochrane Library (from inception up to March 2017) using combinations of the terms "randomized controlled trials", "dexketoprofen", "celecoxib", "etoricoxib", "parecoxib" and "acute pain". Single-dose dexketoprofen trometamol provides effective analgesia in the treatment of acute pain, such as postoperative pain (dental and non-dental surgery), renal colic, acute musculoskeletal disorders and dysmenorrhoea, and reduces opioid consumption in the postoperative setting. It has a rapid onset of action (within 30 minutes) and is well tolerated during short-term treatment. Direct comparisons with COX-2 inhibitors are lacking; however, the efficacy and tolerability of single-dose dexketoprofen trometamol appears to be consistent with that seen with celecoxib, etoricoxib and parecoxib in the acute pain setting. In conclusion, dexketoprofen trometamol appears to provide similar analgesic efficacy to COX-2 inhibitors when used to treat acute pain, has a rapid onset of action, is well tolerated, and has an opioid-sparing effect when used as part of a multimodal regimen in the acute pain setting.

  13. Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis.

    Science.gov (United States)

    Tellegen, A R; Rudnik-Jansen, I; Pouran, B; de Visser, H M; Weinans, H H; Thomas, R E; Kik, M J L; Grinwis, G C M; Thies, J C; Woike, N; Mihov, G; Emans, P J; Meij, B P; Creemers, L B; Tryfonidou, M A

    2018-11-01

    Major hallmarks of osteoarthritis (OA) are cartilage degeneration, inflammation and osteophyte formation. COX-2 inhibitors counteract inflammation-related pain, but their prolonged oral use entails the risk for side effects. Local and prolonged administration in biocompatible and degradable drug delivery biomaterials could offer an efficient and safe treatment for the long-term management of OA symptoms. Therefore, we evaluated the disease-modifying effects and the optimal dose of polyesteramide microspheres delivering the COX-2 inhibitor celecoxib in a rat OA model. Four weeks after OA induction by anterior cruciate ligament transection and partial medial meniscectomy, 8-week-old female rats (n = 6/group) were injected intra-articular with celecoxib-loaded microspheres at three dosages (0.03, 0.23 or 0.39 mg). Unloaded microspheres served as control. During the 16-week follow-up, static weight bearing and plasma celecoxib concentrations were monitored. Post-mortem, micro-computed tomography and knee joint histology determined progression of synovitis, osteophyte formation, subchondral bone changes, and cartilage integrity. Systemic celecoxib levels were below the detection limit 6 days upon delivery. Systemic and local adverse effects were absent. Local delivery of celecoxib reduced the formation of osteophytes, subchondral sclerosis, bone cysts and calcified loose bodies, and reduced synovial inflammation, while cartilage histology was unaffected. Even though the effects on pain could not be evualated directly in the current model, our results suggest the application of celecoxib-loaded microspheres holds promise as novel, safe and effective treatment for inflammation and pain in OA.

  14. Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Heumen, Bjorn W.H. van, E-mail: b.vanheumen@mdl.umcn.nl [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Roelofs, Hennie M.J.; Morsche, Rene H.M. te [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Marian, Brigitte [Institute of Cancer Research, Wien University, Vienna (Austria); Nagengast, Fokko M.; Peters, Wilbert H.M. [Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-04-15

    Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14-17%, p < 0.01). A more pronounced decrease (23-27%, p < 0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p < 0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. -- Highlights: Black-Right-Pointing-Pointer Celecoxib and UDCA acid co-treatment decreases cell growth in colon tumor cells. Black-Right-Pointing-Pointer UDCA enriched 'artificial bile' decreases LT-97 cell growth only in presence of celecoxib. Black-Right-Pointing-Pointer PCNA, caspase-3, nor COX-2 seem to be involved in the observed changes in cell growth.

  15. Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells

    International Nuclear Information System (INIS)

    Heumen, Bjorn W.H. van; Roelofs, Hennie M.J.; Morsche, René H.M. te; Marian, Brigitte; Nagengast, Fokko M.; Peters, Wilbert H.M.

    2012-01-01

    Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14–17%, p < 0.01). A more pronounced decrease (23–27%, p < 0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to ‘artificial bile’ enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with ‘artificial bile’ enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p < 0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. -- Highlights: ► Celecoxib and UDCA acid co-treatment decreases cell growth in colon tumor cells. ► UDCA enriched ‘artificial bile’ decreases LT-97 cell growth only in presence of celecoxib. ► PCNA, caspase-3, nor COX-2 seem to be involved in the observed changes in cell growth.

  16. Celecoxib Induced Tumor Cell Radiosensitization by Inhibiting Radiation Induced Nuclear EGFR Transport and DNA-Repair: A COX-2 Independent Mechanism

    International Nuclear Information System (INIS)

    Dittmann, Klaus H.; Mayer, Claus; Ohneseit, Petra A.; Raju, Uma; Andratschke, Nickolaus H.; Milas, Luka; Rodemann, H. Peter

    2008-01-01

    Purpose: The purpose of the study was to elucidate the molecular mechanisms mediating radiosensitization of human tumor cells by the selective cyclooxygenase (COX)-2 inhibitor celecoxib. Methods and Materials: Experiments were performed using bronchial carcinoma cells A549, transformed fibroblasts HH4dd, the FaDu head-and-neck tumor cells, the colon carcinoma cells HCT116, and normal fibroblasts HSF7. Effects of celecoxib treatment were assessed by clonogenic cell survival, Western analysis, and quantification of residual DNA damage by γH 2 AX foci assay. Results: Celecoxib treatment resulted in a pronounced radiosensitization of A549, HCT116, and HSF7 cells, whereas FaDu and HH4dd cells were not radiosensitized. The observed radiosensitization could neither be correlated with basal COX-2 expression pattern nor with basal production of prostaglandin E2, but was depended on the ability of celecoxib to inhibit basal and radiation-induced nuclear transport of epidermal growth factor receptor (EGFR). The nuclear EGFR transport was strongly inhibited in A549-, HSF7-, and COX-2-deficient HCT116 cells, which were radiosensitized, but not in FaDu and HH4dd cells, which resisted celecoxib-induced radiosensitization. Celecoxib inhibited radiation-induced DNA-PK activation in A549, HSF7, and HCT116 cells, but not in FaDu and HH4dd cells. Consequentially, celecoxib increased residual γH2AX foci after irradiation, demonstrating that inhibition of DNA repair has occurred in responsive A549, HCT116, and HSF7 cells only. Conclusions: Celecoxib enhanced radiosensitivity by inhibition of EGFR-mediated mechanisms of radioresistance, a signaling that was independent of COX-2 activity. This novel observation may have therapeutic implications such that COX-2 inhibitors may improve therapeutic efficacy of radiation even in patients whose tumor radioresistance is not dependent on COX-2

  17. The tritium labelling of ibuprofen by heterogeneous catalytic exchange

    International Nuclear Information System (INIS)

    Santamaria, J.; Rebollo, D.V.; Rivera, P.; Estaban, M.

    1986-01-01

    The tritium labelling of 2-(4-isobutylphenyl) propionic acid (ibuprofen) was performed. The method employed was heterogeneous catalytic exchange between ibuprofen and tritiated water. Prior to labelling, thermic stability of ibuprofen was studied. Purification was accomplished through thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). Concentration, purity and specific activity of the labelled compound were determined by ultraviolet, HPLC and liquid scintillation techniques. (author)

  18. Chrysin alleviates testicular dysfunction in adjuvant arthritic rats via suppression of inflammation and apoptosis: Comparison with celecoxib

    Energy Technology Data Exchange (ETDEWEB)

    Darwish, Hebatallah A. [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Arab, Hany H., E-mail: hany.arab@pharma.cu.edu.eg [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Abdelsalam, Rania M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt)

    2014-09-01

    Long standing rheumatoid arthritis (RA) is associated with testicular dysfunction and subfertility. Few studies have addressed the pathogenesis of testicular injury in RA and its modulation by effective agents. Thus, the current study aimed at evaluating the effects of two testosterone boosting agents; chrysin, a natural flavone and celecoxib, a selective COX-2 inhibitor, in testicular impairment in rats with adjuvant arthritis, an experimental model of RA. Chrysin (25 and 50 mg/kg) and celecoxib (5 mg/kg) were orally administered to Wistar rats once daily for 21 days starting 1 h before arthritis induction. Chrysin suppressed paw edema with comparable efficacy to celecoxib. More important, chrysin, dose-dependently and celecoxib attenuated the testicular injury via reversing lowered gonadosomatic index and histopathologic alterations with preservation of spermatogenesis. Both agents upregulated steroidogenic acute regulatory (StAR) mRNA expression and serum testosterone with concomitant restoration of LH and FSH. Furthermore, they suppressed inflammation via abrogation of myeloperoxidase, TNF-α and protein expression of COX-2 and iNOS besides elevation of IL-10. Alleviation of the testicular impairment was accompanied with suppression of oxidative stress via lowering testicular lipid peroxides and nitric oxide. With respect to apoptosis, both agents downregulated FasL mRNA expression and caspase-3 activity in favor of cell survival. For the first time, these findings highlight the protective effects of chrysin and celecoxib against testicular dysfunction in experimental RA which were mediated via boosting testosterone in addition to attenuation of testicular inflammation, oxidative stress and apoptosis. Generally, the 50 mg/kg dose of chrysin exerted comparable protective actions to celecoxib. - Highlights: • Chrysin and celecoxib alleviated testicular suppression in adjuvant arthritis. • They attenuated histopathological damage and preserved spermatogenesis

  19. Celecoxib Monotherapy Maintained Small Intestinal Mucosa Better Compared With Loxoprofen Plus Lansoprazole Treatment: A Double-blind, Randomized, Controlled Trial.

    Science.gov (United States)

    Fujimori, Shunji; Hanada, Ryuzo; Hayashida, Mari; Sakurai, Toshiyuki; Ikushima, Ippei; Sakamoto, Choitsu

    2016-03-01

    The aim of this study was to compare celecoxib with loxoprofen for protection of small intestine. RCT studies report that COX-2 selective inhibitor celecoxib induces fewer small intestinal injuries than nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). Loxoprofen is a prodrug nonselective NSAID developed to protect upper gastrointestinal tract. A total of 150 healthy volunteers (40 to 70 y) were enrolled. After medical checkup including laboratory data, subjects were randomly assigned to celecoxib (200 mg daily) or loxoprofen (180 mg daily) plus lansoprazole (15 mg daily). All drugs were prepared using inactive capsules. After randomization, all subjects were first examined by baseline capsule endoscopy (CE). After 14 days, subjects underwent posttreatment CE. We compared baseline and posttreatment CE findings of the 2 groups. All CE data were evaluated blindly by 3 reviewers. Pretreatment and posttreatment laboratory variables were also compared. A total of 74 subjects (49±6 y, F/M: 36/38) were enrolled in celecoxib group and 76 subjects (49±7 y, F/M: 39/37)in loxoprofen group. Five in celecoxib group and 4 in loxoprofen group were excluded from CE analysis mainly due to incomplete CE. The percentage of subjects with at least 1 posttreatment mucosal break was lower in celecoxib group (10%) than in loxoprofen group (49%) (Plansoprazole combination therapy (UMIN: 000007936).

  20. Tramadol versus Celecoxib for reducing pain associated with outpatient hysteroscopy: a randomized double-blind placebo-controlled trial.

    Science.gov (United States)

    Hassan, A; Wahba, A; Haggag, H

    2016-01-01

    Which is better, Tramadol or Celecoxib, in reducing pain associated with outpatient hysteroscopy? Both Tramadol and Celecoxib are effective in reducing pain associated with outpatient hysteroscopy but Celecoxib may be better tolerated. Pain is the most common cause of failure of outpatient hysteroscopy. A systematic review and meta-analysis showed that local anaesthetics were effective in reducing pain associated with hysteroscopy but there was insufficient evidence to support the use of oral analgesics, opioids and non-steroidal anti-inflammatory drugs, to reduce hysteroscopy-associated pain and further studies were recommended. This was a randomized double-blind placebo-controlled trial with balanced randomization (allocation ratio 1:1:1) conducted in a university hospital from May 2014 to November 2014. Two hundred and ten women who had diagnostic outpatient hysteroscopy were randomly divided into three equal groups: Group 1 received oral Tramadol 100 mg, group 2 received Celecoxib 200 mg and group 3 received an oral placebo. All the drugs were given 1 h before the procedure. A patient's perception of pain was assessed during the procedure, immediately afterwards and 30 min after the procedure with the use of a visual analogue scale (VAS). There was a significant difference in the pain scores among the groups during the procedure, immediately afterwards and 30 min after the procedure (Ppain scores when compared with the placebo during the procedure (mean difference = 1.54, 95% confidence interval (CI) (0.86, 2.22), P pain scores than the placebo during the procedure (mean difference = 1.28, 95% CI (0.62, 1.94), P pain scores between Tramadol and Celecoxib at any time. Time until no pain differed significantly among the groups (P = 0.01); it was shorter with both Tramadol and Celecoxib groups when compared with placebo (P = 0.002 and 0.046, respectively). The procedure failed to be completed in one patient in the placebo group but no failure to complete the

  1. Ibuprofen - a Safe Analgesic During Cardiac Surgery Recovery?

    DEFF Research Database (Denmark)

    Qazi, Saddiq Mohammad; Sindby, Eske Jesper; Nørgaard, Martin Agge

    2015-01-01

    were undergoing cardiac surgery for the first time, were randomly allocated either to a regimen of slow-release oxycodone (10 mg twice daily) or slow-release ibuprofen (800 mg twice daily) combined with lansoprazole. Data relating to blood-tests, angiographies, surgical details and administered...... if short term slow release ibuprofen combined with lansoprazole treatment is used when compared to an oxycodone based regimen. Renal function should, however, be closely monitored and in the event of any decrease in renal function ibuprofen must be discontinued....

  2. Validated RP-HPLC Method for the Assay of Etoricoxib (A Non-Steroidal Anti-Inflammatory Drug in Pharmaceutical Dosage Forms

    Directory of Open Access Journals (Sweden)

    Srinivasu Topalli

    2012-01-01

    Full Text Available A simple, accurate, sensitive and reproducible reverse phase high performance liquid chromatographic method has been developed for the quantitative determination of Etoricoxib in pharmaceutical dosage forms. The assay was performed on Hypersil ODS C-18 (250 x 4.6 mm., 5µm particle size column using acetonitrile and potassium dihydrogen phosphate buffer (pH 4.2 (46:54 % v/v as mobile phase with UV detection at 280 nm (flow rate 1.2 ml/min. Bromhexine was used as an internal standard. Quantization was achieved by measurement of the peak area ratio of the drug to the internal standard. The limit of detection (LOD and the limit of quantification (LOQ were 0.0704 µg ml-1 and 0.2134 µg ml-1 respectively. Each analysis required no longer than 10 minutes. The calibration curve was linear over the concentration range from 0.5-85.0 µg ml-1. The retention times of Etoricoxib and Bromhexine were found to be 3.083 and 7.631 minutes respectively. The proposed method was validated according to the ICH guidelines and can be used successfully to analyse marketed formulations.

  3. Effect of Ibuprofen on masking endodontic diagnosis.

    Science.gov (United States)

    Read, Jason K; McClanahan, Scott B; Khan, Asma A; Lunos, Scott; Bowles, Walter R

    2014-08-01

    An accurate diagnosis is of upmost importance before initiating endodontic treatment; yet, there are occasions when the practitioner cannot reproduce the patient's chief complaint because the patient has become asymptomatic. Ibuprofen taken beforehand may "mask" or eliminate the patient's symptoms. In fact, 64%-83% of patients with dental pain take analgesics before seeing a dentist. The purpose of this study was to examine the possible "masking" effect of ibuprofen on endodontic diagnostic tests. Forty-two patients with endodontic pain underwent testing (cold, percussion, palpation, and bite force measurement) and then received either placebo or 800 mg ibuprofen. Both patients and operators were blinded to the medication received. One hour later, diagnostic testing was repeated and compared with pretreatment testing. Ibuprofen affected testing values for vital teeth by masking palpation 40%, percussion 25%, and cold 25% on affected teeth with symptomatic irreversible pulpitis and symptomatic apical periodontitis. There was no observed masking effect in the placebo group on palpation, percussion, or cold values. When nonvital teeth were included, the masking effect of ibuprofen was decreased. However, little masking occurred with the bite force measurement differences. Analgesics taken before the dental appointment can affect endodontic diagnostic testing results. Bite force measurements can assist in identifying the offending tooth in cases in which analgesics "mask" the endodontic diagnosis. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  4. Bioequivalence assessment of two formulations of ibuprofen

    KAUST Repository

    Al-Talla, Zeyad

    2011-10-19

    Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz , produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen , manufactured by Boots Company, Nottingham, UK. Methods and results: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference) of ibuprofen (100 mg ibuprofen/5 mL suspension) were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC) parameters were found to be within the predetermined acceptable interval of 80%-125% set by the US Food and Drug Administration. Conclusion: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and, therefore, Doloraz was considered bioequivalent to Brufen. 2011 Al-Talla et al, publisher and licensee Dove Medical Press Ltd.

  5. Celecoxib, but not indomethacin, ameliorates the hypertensive and perivascular fibrotic actions of cyclosporine in rats: Role of endothelin signaling

    International Nuclear Information System (INIS)

    El-Mas, Mahmoud M.; Helmy, Maged W.; Ali, Rabab M.; El-Gowelli, Hanan M.

    2015-01-01

    The immunosuppressant drug cyclosporine (CSA) is used with nonsteroidal antiinflammatory drugs (NSAIDs) in arthritic conditions. In this study, we investigated whether NSAIDs modify the deleterious hypertensive action of CSA and the role of endothelin (ET) receptors in this interaction. Pharmacologic, protein expression, and histopathologic studies were performed in rats to investigate the roles of endothelin receptors (ET A /ET B ) in the hemodynamic interaction between CSA and two NSAIDs, indomethacin and celecoxib. Tail-cuff plethysmography measurements showed that CSA (20 mg kg −1 day −1 , 10 days) increased systolic blood pressure (SBP) and heart rate (HR). CSA hypertension was associated with renal perivascular fibrosis and divergent changes in immunohistochemical signals of renal arteriolar ET A (increases) and ET B (decreases) receptors. While these effects of CSA were preserved in rats treated concomitantly with indomethacin (5 mg kg −1 day −1 ), celecoxib (10 mg kg −1 day −1 ) abolished the pressor, tachycardic, and fibrotic effects of CSA and normalized the altered renal ET A /ET B receptor expressions. Selective blockade of ET A receptors by atrasentan (5 mg kg −1 day −1 ) abolished the pressor response elicited by CSA or CSA plus indomethacin. Alternatively, BQ788 (ET B receptor blocker, 0.1 mg kg −1 day −1 ) caused celecoxib-sensitive elevations in SBP and potentiated the pressor response evoked by CSA. Together, the improved renovascular fibrotic and endothelin receptor profile (ET A downregulation and ET B upregulation) mediate, at least partly, the protective effect of celecoxib against the hypertensive effect of CSA. Clinically, the use of celecoxib along with CSA in the management of arthritic conditions might provide hypertension-free regimen. - Highlights: • Chronic CSA causes hypertension and renal perivascular fibrosis in rats. • CSA increased and decreased renal ET A and ET B receptor expression, respectively. • CSA

  6. Optimization of Process Variables for Grinding of Ibuprofen using Response Surface Methodology

    International Nuclear Information System (INIS)

    Sim, Chol-Ho

    2013-01-01

    Ibuprofen, non-steroidal anti-inflammatory drugs; NSAIDs, is a highly crystalline substance with the pharmaceutical properties of poor solubility and low bioavailability. The size reduction of ibuprofen is needed to improve the solubility. The objective of this study is to optimize the grinding condition of ibuprofen. Grinding of ibuprofen was carried out using a planetary mill. Grinding parameters were optimized using Box-Behnken experimental design method. The physical characteristics of ground ibuprofen were investigated for the particle size by particle size analyzer, for the crystal size by X-ray diffraction (XRD), and for the tensile strength by tensile/compression tester. The optimum conditions for the milling of ibuprofen were 290 rpm of the revolution number of mill, 24.6 g of the weight of sample, and 10minutes of grinding time. The measured value of the particle size of ground ibuprofen at these optimum conditions was 13.5 µm. The results showed that the crystal size of ibuprofen was reduced by the planetary milling process. In case the relative density of the tablets formulated of ground ibuprofen was range of 0.85-0.90, the tensile strength of them was range of 12-14 Kg f /cm 2

  7. Treatment of ibuprofen intoxication in a dog via therapeutic plasma exchange.

    Science.gov (United States)

    Walton, Stuart; Ryan, Kirk A; Davis, Jennifer L; Acierno, Mark

    2017-07-01

    To describe the treatment of ibuprofen intoxication with therapeutic plasma exchange in a dog (TPE). A 13-year-old male neutered mixed breed dog presented after ingesting approximately 200 mg/kg of ibuprofen. Treatment consisted of supportive medical therapy with IV fluids, gastrointestinal protectants, antiemetics and prostaglandin analogs, and TPE. A cycle of TPE was performed over 180 minutes, achieving 1.5 plasma volume exchanges. During therapy, heparinized blood and effluent samples were collected. Ibuprofen concentrations were determined in the samples by high-pressure liquid chromatography. Post TPE, the dog was continued on supportive medical therapy and was discharged 96 hours after the overdose. This report describes the use of TPE as an adjunct for ibuprofen intoxication. An 85% reduction in plasma ibuprofen concentration occurred and recovery from a potentially lethal ingestion of ibuprofen was achieved with TPE and supportive care. TPE should be considered when presented with acute ibuprofen intoxication due to the rapid and efficacious nature of therapy. © Veterinary Emergency and Critical Care Society 2017.

  8. The interplay between GRP78 expression and Akt activation in human colon cancer cells under celecoxib treatment.

    Science.gov (United States)

    Tian, Shaobo; Chang, Weilong; Du, Hansong; Bai, Jie; Sun, Zhenhai; Zhang, Qing; Wang, Hui; Zhu, Guangsheng; Tao, Kaixiong; Long, Yueping

    2015-10-01

    It has been reported previously that celecoxib shows antitumor effects in many types of cancers. Here, we detected its effects on DLD-1 and SW480 (two human colon cancer cell lines) and investigated the dynamic relationship between the 78-kDa glucose-regulatory protein (GRP78) and the phosphoinositide 3-kinase (PI3K)/Akt pathway. Gene expression was detected by real-time PCR and western blot analysis; the cytotoxicity was determined by the MTT assay and flow cytometry. First, the results showed that celecoxib induced cytotoxicity in a dose-dependent and time-dependent manner. Furthermore, we found the celecoxib-triggered unfolded protein response and the bidirectional regulation of Akt activation in both cell lines. Inhibiting the Akt activation by the PI3K inhibitor LY294002 markedly enhanced GRP78 expression. Besides, silencing the GRP78 expression regulated Akt activation in a time-dependent manner and increased the induction of the C/EBP homologous protein (CHOP) as well as considerably promoted celecoxib-induced apoptosis. In conclusion, these findings provide evidence that under the celecoxib treatment, GRP78 plays a protective role by modulating Akt activation and abrogating CHOP expression. However, Akt activation can provide a feedback loop to inhibit GRP78 expression. These studies can lead to novel therapeutic strategies for human colon cancer.

  9. Acute pain management: acetaminophen and ibuprofen are often under-dosed.

    Science.gov (United States)

    Milani, Gregorio P; Benini, Franca; Dell'Era, Laura; Silvagni, Davide; Podestà, Alberto F; Mancusi, Rossella Letizia; Fossali, Emilio F

    2017-07-01

    Most children with pain are managed by either acetaminophen or ibuprofen. However, no study has so far investigated if children are prescribed adequate doses of acetaminophen or ibuprofen in emergency department. Aim of this retrospective study was to investigate the prevalence of under-dosage of these drugs in children presenting with pain in emergency department. Children initially prescribed with acetaminophen or ibuprofen for pain management were included. The χ 2 automatic interaction detection method was used considering the percentage variation from the minimum of the appropriate dose as dependent variable while prescribed drug, age, gender, body weight, type of hospital (pediatric or general), and availability of internal guidelines on pediatric pain management in the emergency department as independent variables. Data on 1471 children managed for pain were available. Under-dosage was prescribed in 893 subjects (61%), of whom 577 were prescribed acetaminophen and 316 ibuprofen. The use of acetaminophen suppositories, body weight 40 kg, and the use of oral ibuprofen identified clusters of children associated with under-dosage prescription. Prescription of acetaminophen and ibuprofen was frequently under-dosed. The use of suppositories, lower and higher body weight, and the use of ibuprofen were associated with under-dosage. Under-dosing may reflect prescription of anti-pyretic doses. Agenzia Italiana del Farmaco-Observational Study Register (RSO). Registration code: PIERRE/1 What is Known: • Pain is frequent in children presented to emergency department. • International recommendations on pain management are often not implemented. What is New: • Acetaminophen and ibuprofen were frequently underdosed in children prescribed for pain in the Italian emergency departments. • Under-dosage may be related to the habit of using acetaminophen and ibuprofen in the recommended range for fever treatment.

  10. MODELLING DICLOFENAC AND IBUPROFEN RESIDUES IN MAJOR ESTONIAN SEASIDE CITIES

    Directory of Open Access Journals (Sweden)

    Erki Lember

    2016-06-01

    Full Text Available A theoretical model was developed to model the fate of two common pharmaceutical residues: diclofenac and ibuprofen in eight Estonian seaside cities that discharge their wastewaters directly into the Baltic Sea. The consumption rates of the active ingredients of diclofenac and ibuprofen from 2006-2014 were analysed. A decrease of 19.9% for diclofenac consumption and an increase of 14.1% for ibuprofen were found. The fate of diclofenac and ibuprofen were modelled by considering the human metabolism removal rate for pharmaceuticals, the removal rate of diclofenac and ibuprofen in activated sludge wastewater treatment plants (WWTP and annual flow rates. An average decrease from 1 to 0.8 µg/l (decrease of 20% for diclofenac and an increase from 11.4 to 13.4 µg/l (increase of 14.9% for ibuprofen for the concentration in the effluents of the WWTP were modelled. The model gives us a good overview about the theoretical concentrations of pharmaceutical residues in the environment and is helpful for evaluating environmental impacts.

  11. Optimization of Process Variables for Grinding of Ibuprofen using Response Surface Methodology

    Energy Technology Data Exchange (ETDEWEB)

    Sim, Chol-Ho [Sangji University, Wonju (Korea, Republic of)

    2013-12-15

    Ibuprofen, non-steroidal anti-inflammatory drugs; NSAIDs, is a highly crystalline substance with the pharmaceutical properties of poor solubility and low bioavailability. The size reduction of ibuprofen is needed to improve the solubility. The objective of this study is to optimize the grinding condition of ibuprofen. Grinding of ibuprofen was carried out using a planetary mill. Grinding parameters were optimized using Box-Behnken experimental design method. The physical characteristics of ground ibuprofen were investigated for the particle size by particle size analyzer, for the crystal size by X-ray diffraction (XRD), and for the tensile strength by tensile/compression tester. The optimum conditions for the milling of ibuprofen were 290 rpm of the revolution number of mill, 24.6 g of the weight of sample, and 10minutes of grinding time. The measured value of the particle size of ground ibuprofen at these optimum conditions was 13.5 µm. The results showed that the crystal size of ibuprofen was reduced by the planetary milling process. In case the relative density of the tablets formulated of ground ibuprofen was range of 0.85-0.90, the tensile strength of them was range of 12-14 Kg{sub f}/cm{sup 2}.

  12. Growth inhibition and radiosensitization of Celecoxib in nasopharyngeal caricnoma cell line CNE-2

    International Nuclear Information System (INIS)

    Xu Xinhua; Yi Fang; Fu Xiangyang; Zhang Xiaohong; Wang Yanlin; Zhang Changju; Du Jingtao

    2009-01-01

    Objective: To investigate the growth inhibition and radiosensitization of Celecoxib in human nasopharyngeal carcinoma cell line CNE-2. Methods: CNE-2 growth inhibition by Celecoxib was evaluated by MTT method. Apoptosis-related changes in morphology were observed by transmission electron microscopy(TEM). Cell cycle distribution and apoptosis rate were measured by flowcytometry(FCM). The expression of COX-2 protein was observed by SP method after the treatment of Celecoxib. Cells were randomly planted into four groups: irradiation control (Ci), drug group (Cd), irradiation group (R), and Celecoxib plus irradiation group (D + R). Single irradiation of 2,4,6,8, and 10 Gy were administered for colonogenic assay. Cell cycle distribution and apoptosis rate were analyzed at 6 Gy irradiation. Results: The growth of CNE-2 cell was inhibited by celecoxib in a dose-and time-dependent manner, the IC 50 was 80 μmol/L. After the treatment, cell ratio of G 0 and G 1 phases wasinereased (47.03 ± 2.76 vs 56.17 ± 1.95, t=4.68, P=0.010), whereas the ratio of S and G 2 /M phases was decreased (33.07 ± 1.86 vs 24.87 ± 1.76, t=5.54,P =0.010;19.30 ± 0.53:17.73 ± 0.83, t=2.75, P=0.050), and the apoptosis rate was increased (1.57 ± 0.47:10.47 ± 0.31,t=27.39, P=0.000) in a dose-dependent manner. Apoptosis with nuclear chromatin condensation, fragmentation and cell shrinkage was found by TEM. SP method showed that Celeib decreased COX-2 expression (17.48 ± 0.34 vs 12.82 ± 0.51, t=13.20, P=0.00). The sensitivity ratio (D 0 ) was 1.15. FCM showed that the percentage of cells in G 2 /M phase was significanty more in R and D + R groups than in Ci and Cd groups (68.00 ± 1.65, 54.27 ± 5.74,17.60 ± 0.80,14.86 ± 1.23, t=47.70,P=0.000; t=11.63, P=0.000), and also significantly different between R group and D + R group (t=3.99, P= 0.020). The apoptosis rate was higher in R and D + R groups than Ci and Cd groups(4.83 ± 0.97,9.50 ± 1.35,1.33 ± 0.86 and 2.28 ± 0.42, t=4.67, P=0.010; t

  13. Fulvic Acid Mediated Photolysis of Ibuprofen in Water.

    Science.gov (United States)

    Photolysis of the nonsteroidal anti-inflammatory drug ibuprofen was studied in solutions of fulvic acid (FA) isolated from Pony Lake, Antarctica; Suwannee River, GA, USA; and Old Woman Creek, OH, USA. At an initial concentration of 10 µM ibuprofen degrades by direct photolysis...

  14. Quantitative proteomic analysis of ibuprofen-degrading Patulibacter sp. strain I11

    DEFF Research Database (Denmark)

    Almeida, Barbara; Kjeldal, Henrik; Lolas, Ihab Bishara Yousef

    2013-01-01

    was identified and quantified by gel based shotgun-proteomics. In total 251 unique proteins were quantitated using this approach. Biological process and pathway analysis indicated a number of proteins that were up-regulated in response to active degradation of ibuprofen, some of them are known to be involved...... in the degradation of aromatic compounds. Data analysis revealed that several of these proteins are likely involved in ibuprofen degradation by Patulibacter sp. strain I11.......Ibuprofen is the third most consumed pharmaceutical drug in the world. Several isolates have been shown to degrade ibuprofen, but very little is known about the biochemistry of this process. This study investigates the degradation of ibuprofen by Patulibacter sp. strain I11 by quantitative...

  15. COX-2 inhibition is neither necessary nor sufficient for celecoxib to suppress tumor cell proliferation and focus formation in vitro

    Directory of Open Access Journals (Sweden)

    Petasis Nicos A

    2008-05-01

    Full Text Available Abstract Background An increasing number of reports is challenging the notion that the antitumor potential of the selective COX-2 inhibitor celecoxib (Celebrex® is mediated primarily via the inhibition of COX-2. We have investigated this issue by applying two different analogs of celecoxib that differentially display COX-2-inhibitory activity: the first analog, called unmethylated celecoxib (UMC, inhibits COX-2 slightly more potently than its parental compound, whereas the second analog, 2,5-dimethyl-celecoxib (DMC, has lost the ability to inhibit COX-2. Results With the use of glioblastoma and pancreatic carcinoma cell lines, we comparatively analyzed the effects of celecoxib, UMC, and DMC in various short-term (≤48 hours cellular and molecular studies, as well as in long-term (≤3 months focus formation assays. We found that DMC exhibited the most potent antitumor activity; celecoxib was somewhat less effective, and UMC clearly displayed the overall weakest antitumor potential in all aspects. The differential growth-inhibitory and apoptosis-stimulatory potency of these compounds in short-term assays did not at all correlate with their capacity to inhibit COX-2, but was closely aligned with their ability to trigger endoplasmic reticulum stress (ERS, as indicated by the induction of the ERS marker CHOP/GADD153 and activation of the ERS-associated caspase 7. In addition, we found that these compounds were able to restore contact inhibition and block focus formation during long-term, chronic drug exposure of tumor cells, and this was achieved at sub-toxic concentrations in the absence of ERS or inhibition of COX-2. Conclusion The antitumor activity of celecoxib in vitro did not involve the inhibition of COX-2. Rather, the drug's ability to trigger ERS, a known effector of cell death, might provide an alternative explanation for its acute cytotoxicity. In addition, the newly discovered ability of this drug to restore contact inhibition and

  16. Effects of NSAIDs and paracetamol (acetaminophen on protein kinase C epsilon translocation and on substance P synthesis and release in cultured sensory neurons

    Directory of Open Access Journals (Sweden)

    Vellani V

    2013-02-01

    Full Text Available Vittorio Vellani,1 Silvia Franchi,2 Massimiliano Prandini,1 Sarah Moretti,2 Mara Castelli,2 Chiara Giacomoni,3 Paola Sacerdote21Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 2Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; 3Department of Economics and Technology, University of the Republic of San Marino, Republic of San MarinoAbstract: Celecoxib, diclofenac, ibuprofen, and nimesulide are nonsteroidal anti-inflammatory drugs (NSAIDs very commonly used for the treatment of moderate to mild pain, together with paracetamol (acetaminophen, a very widely used analgesic with a lesser anti-inflammatory effect. In the study reported here, we tested the efficacy of celecoxib, diclofenac, and ibuprofen on preprotachykinin mRNA synthesis, substance P (SP release, prostaglandin E2 (PGE2 release, and protein kinase C epsilon (PKCε translocation in rat cultured sensory neurons from dorsal root ganglia (DRGs. The efficacy of these NSAIDs was compared with the efficacy of paracetamol and nimesulide in in vitro models of hyperalgesia (investigated previously. While nimesulide and paracetamol, as in previous experiments, decreased the percentage of cultured DRG neurons showing translocation of PKCε caused by 100 nM thrombin or 1 µM bradykinin in a dose-dependent manner, the other NSAIDs tested did not have a significant effect. The amount of SP released by peptidergic neurons and the expression level of preprotachykinin mRNA were assessed in basal conditions and after 70 minutes or 36 hours of stimulation with an inflammatory soup (IS containing potassium chloride, thrombin, bradykinin, and endothelin-1. The release of SP at 70 minutes was inhibited only by nimesulide, while celecoxib and diclofenac were effective at 36 hours. The mRNA basal level of the SP precursor preprotachykinin expressed in DRG neurons was reduced only by nimesulide, while the

  17. Radioiodination of ibuprofen with 125I and its biological behavior in mice

    International Nuclear Information System (INIS)

    Amin, A. M.; Abd El-bary, A.; Shoukry, M. and other

    2012-12-01

    A procedure for radioiodination of Ibuprofen with iodine-125 is carried out via an electrophilic substitution reaction. The reaction parameters were studied Ibuprofen concentration, pH of the reaction mixture, reaction time temperature, and different oxidizing agents to optimize the conditions for the labeling of Ibuprofen to abstain a high radiochemical yield of 1 25I -Ibuprofen (1 25I -Ib up). Using 3.7 MBq of of Na 1 25I , 100μg of ibuprofen as substrate and 100μg of iodogen as oxidizing agent in ethanol at 60 O C for 10 min, a maximum radiochemical yield of 1 25I -Ib up (78%) was obtained. The labeled compound was separated and purified from inactive Ibuprofen by means of high-pressure liquid chromatography (HPLC). The biological distribution in normal and inflamed mice indicates the suitability of radioiodinated Ibuprofen for imaging of inflammation only induced with turpentine oil. (Author)

  18. Premarketing surveillance of ibuprofen suppositories in febrile children.

    Science.gov (United States)

    Hadas, Dan; Youngster, Ilan; Cohen, Avner; Leibovitch, Eugene; Shavit, Itai; Erez, Ilan; Uziel, Yosef; Berkovitch, Matitiahu

    2011-03-01

    In many countries, ibuprofen is available only in oral formulations. The authors aimed to investigate parental satisfaction and possible adverse reactions among children receiving newly marketed ibuprofen suppositories, prior to their arrival at the pharmaceutical points of distribution. Children needing antipyretic medication were recruited from 11 pediatric wards and clinics in Israel. Each patient received ibuprofen suppositories (5-10 mg/kg/dose) after completing a data collection form. After 3 to 7 days of treatment, information regarding parent satisfaction, possible adverse reactions, and concomitant use of drugs was obtained. Overall, 490 children completed the study. Parents' satisfaction was high (4.5 ± 0.47 on a scale of 1-5), and 92.2% reported that they would use the medication in the future. Adverse reactions were reported in 8 patients (1.63%, 95% confidence interval = 1.77-3.25), the most common being diarrhea. Rectal administration of ibuprofen suppositories is well tolerated and overall satisfaction and the repeated expected use were high.

  19. Clinically relevant pain relief with an ibuprofen-releasing foam dressing

    DEFF Research Database (Denmark)

    Fogh, Karsten; Andersen, Maibritt B; Bischoff-Mikkelsen, Morten

    2012-01-01

    The objective of this 6-week, 120-patient, double-blind, randomized, controlled trial was to investigate if a foam dressing with ibuprofen provided clinically relevant pain relief (PAR) for exuding, painful venous leg ulcers in comparison with a similar foam dressing without ibuprofen. Primary......) and the corresponding number needed to treat (NNT). Wound-related parameters such as ulcer healing, ulcer area reduction, and peri-ulcer skin condition as well as adverse events were recorded during all 6 weeks of the investigation. PAR was significantly greater in the ibuprofen foam group than the comparator group (p...... = 0.0438). There were 34% responders in the ibuprofen foam group vs. 19% in the comparator group (NNT = 6.8). When evening data were analyzed separately to evaluate PAR over daytime, NNT was 5.3. Wound healing parameters and adverse events were comparable. In conclusion, in this study, the ibuprofen...

  20. Differential impairment of aspirin-dependent platelet cyclooxygenase acetylation by nonsteroidal antiinflammatory drugs

    Science.gov (United States)

    Li, Xuanwen; Fries, Susanne; Li, Ruizhi; Lawson, John A.; Propert, Kathleen J.; Diamond, Scott L.; Blair, Ian A.; FitzGerald, Garret A.; Grosser, Tilo

    2014-01-01

    The cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs) may be influenced by interactions with antiplatelet doses of aspirin. We sought to quantitate precisely the propensity of commonly consumed NSAIDs—ibuprofen, naproxen, and celecoxib—to cause a drug–drug interaction with aspirin in vivo by measuring the target engagement of aspirin directly by MS. We developed a novel assay of cyclooxygenase-1 (COX-1) acetylation in platelets isolated from volunteers who were administered aspirin and used conventional and microfluidic assays to evaluate platelet function. Although ibuprofen, naproxen, and celecoxib all had the potential to compete with the access of aspirin to the substrate binding channel of COX-1 in vitro, exposure of volunteers to a single therapeutic dose of each NSAID followed by 325 mg aspirin revealed a potent drug–drug interaction between ibuprofen and aspirin and between naproxen and aspirin but not between celecoxib and aspirin. The imprecision of estimates of aspirin consumption and the differential impact on the ability of aspirin to inactivate platelet COX-1 will confound head-to-head comparisons of distinct NSAIDs in ongoing clinical studies designed to measure their cardiovascular risk. PMID:25385584

  1. Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells

    International Nuclear Information System (INIS)

    Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Gendler, Sandra J; Mukherjee, Pinku

    2005-01-01

    Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E 2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G 0 /G 1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E 2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with reduced vascularization and

  2. Thermodynamic study of complex formation of β-cyclodextrin with ibuprofen by conductometric method and determination of ibuprofen in pharmaceutical drugs

    Directory of Open Access Journals (Sweden)

    Somayeh Heydari

    2017-02-01

    Based on the obtained results, a conductometric method for the determination of ibuprofen in the presence of β-CD at 25 °C was developed in the range of 10−3–10−5 mol dm−1. The method was satisfactorily applied to the quantification of ibuprofen in pharmaceutical preparations.

  3. Impact of pore characteristics of silica materials on loading capacity and release behavior of ibuprofen

    Energy Technology Data Exchange (ETDEWEB)

    Numpilai, Thanapha [Department of Chemical Engineering, Faculty of Engineering, Kasetsart University, Bangkok 10900 (Thailand); Muenmee, Suthaporn [Department of Chemical Engineering, Faculty of Engineering, Kasetsart University, Bangkok 10900 (Thailand); Center for Advanced Studies in Nanotechnology and Its Applications in Chemical Food and Agricultural Industries, Kasetsart University, Bangkok 10900 (Thailand); Witoon, Thongthai, E-mail: fengttwi@ku.ac.th [Department of Chemical Engineering, Faculty of Engineering, Kasetsart University, Bangkok 10900 (Thailand); Center for Advanced Studies in Nanotechnology and Its Applications in Chemical Food and Agricultural Industries, Kasetsart University, Bangkok 10900 (Thailand); NANOTEC-KU-Center of Excellence on Nanoscale Materials Design for Green Nanotechnology, Kasetsart University, Bangkok 10900 (Thailand)

    2016-02-01

    Impact of pore characteristics of porous silica supports on loading capacity and release behavior of ibuprofen was investigated. The porous silica materials and ibuprofen-loaded porous silica materials were thoroughly characterized by N{sub 2}-sorption, thermal gravimetric and derivative weight analyses (TG-DTW), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM) to determine the physical properties of materials, amount of ibuprofen adsorbed and position of ibuprofen. The detailed characterization reveals that the ibuprofen molecules adsorbed inside the mesopores. Increasing the mesopore size from 5 nm to 10 nm increased the ibuprofen loading from 0.74 to 0.85 mmol/g, respectively. Incorporation of macropore into the structure of porous silica materials enhanced the ibuprofen loading capacity of 11.8–20.3%. The ibuprofen-loaded bimodal meso-macroporous silica materials exhibited the highest dissolution of 92 wt.% within an hour. The ibuprofen particles deposited on the external surface of the porous silica materials showed a lower dissolution rate than the ibuprofen adsorbed inside the mesopores due to the formation of ibuprofen crystalline. - Highlights: • Impacts of pore characteristics of supports on adsorption and release of ibuprofen • Increasing mesopore size increased the ibuprofen loading and dissolution rate. • Macropores reduced the diffusion pathway of ibuprofen and dissolution medium.

  4. Impact of pore characteristics of silica materials on loading capacity and release behavior of ibuprofen

    International Nuclear Information System (INIS)

    Numpilai, Thanapha; Muenmee, Suthaporn; Witoon, Thongthai

    2016-01-01

    Impact of pore characteristics of porous silica supports on loading capacity and release behavior of ibuprofen was investigated. The porous silica materials and ibuprofen-loaded porous silica materials were thoroughly characterized by N 2 -sorption, thermal gravimetric and derivative weight analyses (TG-DTW), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM) to determine the physical properties of materials, amount of ibuprofen adsorbed and position of ibuprofen. The detailed characterization reveals that the ibuprofen molecules adsorbed inside the mesopores. Increasing the mesopore size from 5 nm to 10 nm increased the ibuprofen loading from 0.74 to 0.85 mmol/g, respectively. Incorporation of macropore into the structure of porous silica materials enhanced the ibuprofen loading capacity of 11.8–20.3%. The ibuprofen-loaded bimodal meso-macroporous silica materials exhibited the highest dissolution of 92 wt.% within an hour. The ibuprofen particles deposited on the external surface of the porous silica materials showed a lower dissolution rate than the ibuprofen adsorbed inside the mesopores due to the formation of ibuprofen crystalline. - Highlights: • Impacts of pore characteristics of supports on adsorption and release of ibuprofen • Increasing mesopore size increased the ibuprofen loading and dissolution rate. • Macropores reduced the diffusion pathway of ibuprofen and dissolution medium.

  5. Bioequivalence assessment of two formulations of ibuprofen

    Directory of Open Access Journals (Sweden)

    Al-Talla ZA

    2011-10-01

    Full Text Available Zeyad A Al-Talla1, Sabah H Akrawi2, Luke T Tolley3, Salim H Sioud1, Mohammed F Zaater4, Abdul-Hamid M Emwas1 1Analytical and NMR Core Laboratories, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudia Arabia; 2College of Pharmacy, Al-Ain University, Al-Ain, United Arab Emirates; 3Department of Chemistry and Biochemistry, Southern Illinois University Carbondale, Carbondale, IL, USA; 4Department of Chemistry, Jordan University of Science and Technology, Jordan University of Science and Technology, Irbid, Jordan Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz®, produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen®, manufactured by Boots Company, Nottingham, UK. Methods and results: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference of ibuprofen (100 mg ibuprofen/5 mL suspension were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC parameters were found to be within the predetermined acceptable interval of 80%–125% set by the US Food and Drug Administration. Conclusion: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and

  6. Molecularly Imprinted Polymers (MIP for Selective Solid Phase Extraction of Celecoxib in Urine Samples Followed by High Performance Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    Saeedeh Ansari

    2017-09-01

    Full Text Available In this study, for the analysis of human urine samples, a novel method explained for the determination of celecoxib, a nonsteroidal anti-inflammatory drug (NSAID, using molecularly imprinted solid-phase extraction (MISPE coupled with high-performance liquid chromatography (HPLC. The synthesis of the MIP was performed by precipitation polymerization in methacrylic acid (MAA, ethylene glycol dimethacrylate (EGDMA, chloroform, 2,2′-azobisisobutyronitrile (AIBN and celecoxib as the functional monomer, cross-linker monomer, solvent, initiator and target drug, respectively. The celecoxib imprinted polymer was utilized as a specific sorbent for the solid phase extraction (SPE of celecoxib from samples. The molecularly imprinted polymer (MIP performance was compared with the synthesized non-molecularly imprinted polymer (NIP. Scanning electron microscopy (SEM, FT-IR spectroscopy, UV-VIS spectrophotometry and thermogravimetric analysis (TGA/DTG were used for characterizing the synthesized polymers. Moreover, the MISPE procedure parameters such as pH, eluent solvent flow rate, eluent volume and sorbent mass that probably influence the extraction process have been optimized to achieve the highest celecoxib extraction efficiency. The relative standard deviation (RSD %, recovery percent, limit of detection (LOD and limit of quantification (LOQ of this proposed method were 1.12%, 96%, 8 µg L-1 and 26.7 µg L-1, respectively. The proposed MISPE-HPLC-UV method can be used for the separation and enrichment of trace amounts of celecoxib in human urine and biological samples.

  7. Evaluation of a Non-aqueous Ibuprofen-Phospholipid Complex Formulation in Rats.

    Science.gov (United States)

    Li, Chunhua; Xu, Songlin; Liu, Zhidong; Ding, Lingling; Zhao, Xiaobin; Lee, Robert J

    2016-01-01

    In the present study, a non-aqueous ibuprofen-phospholipid complex was developed to reduce the gastrointestinal (GI) toxicity of ibuprofen. A non-aqueous ibuprofen-phospholipid complex (IBU-PC) was prepared by mixing phosal-35SB and ibuprofen. In vitro release behavior was studied using a dissolution apparatus. Irritation to gastrointestinal (GI) tract and pharmacokinetics of IBU-PC were studied in rats. Rapid release of drug occurred with approximately 85% of ibuprofen released from the composition within the first 30 min. The GI injury in IBU-PC-treated rats was minimal compared to those of Advil Liqui-gels-treated group. There was no significant difference between IBU-PC and Motrin-treated groups. The area under the concentration-time curve (AUC0~24) of IBU-PC and Motrin were 366±115 and 391±105 μg/h/ml, respectively. The relative bioavailability of IBU-PC was 94.2%. IBU-PC can decrease GI adverse reaction induced by ibuprofen. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  8. The Effect of Celecoxib on Orthodontic Tooth Movement and Root Resorption in Rat

    Directory of Open Access Journals (Sweden)

    Ahmad Sodagar

    2013-01-01

    Full Text Available Objective: Inhibition of prostaglandin (PGs production leads to decrease in orthodontic tooth movement (OTM. It is not known whether inhibition of cyclooxygenase-1 (COX-1 or cyclooxygenase-2 (COX-2 is the key mechanism for this effect. In this study, the effect of celecoxib, a highly-selective COX-2 inhibitor, was investigated on OTM in rats.Materials and Methods: Four groups of male rats (seven animals in each goup were used in the study. A 5mm-long nickel-titanium closed-coil spring was ligated between the right maxillary incisor and the first molar of each rat to deliver an initial force of 60g. All four groups recieved orthodontic appliances, group 1 received no injections, group 2 received celecoxib injections (0.3 mg in 0.1 ml saline solution, group 3 recieved normal saline injections (0.1 ml saline solution, and group 4 recieved needle penetration without injecting any solution. The local injections were carried out every 3 days for 18 days. All injections were subperiosteal and given in the upper right first molar mucosa. The animals were sacrificed 21 days after appliance insertion and OTM was measured.Results: In the animals treated with celecoxib a statistically significant decrease in OTM was observed compared with the other groups. Histological findings revealed that osteoclast count was significantly lower in group 2 compared with the other groups (P<0.05. The amount of root resorption showed a slight, but nonsignificant decrease in group 3.Conclusion: This study suggests that celecoxib decreases OTM and osteoclast count. This might be the result of COX-2 enzyme inhibition and subsequent decrease in prostaglandin production.

  9. Cubic phase nanoparticles for sustained release of ibuprofen: formulation, characterization, and enhanced bioavailability study

    Science.gov (United States)

    Dian, Linghui; Yang, Zhiwen; Li, Feng; Wang, Zhouhua; Pan, Xin; Peng, Xinsheng; Huang, Xintian; Guo, Zhefei; Quan, Guilan; Shi, Xuan; Chen, Bao; Li, Ge; Wu, Chuanbin

    2013-01-01

    In order to improve the oral bioavailability of ibuprofen, ibuprofen-loaded cubic nanoparticles were prepared as a delivery system for aqueous formulations. The cubic inner structure was verified by cryogenic transmission electron microscopy. With an encapsulation efficiency greater than 85%, the ibuprofen-loaded cubic nanoparticles had a narrow size distribution around a mean size of 238 nm. Differential scanning calorimetry and X-ray diffraction determined that ibuprofen was in an amorphous and molecular form within the lipid matrix. The in vitro release of ibuprofen from cubic nanoparticles was greater than 80% at 24 hours, showing sustained characteristics. The pharmacokinetic study in beagle dogs showed improved absorption of ibuprofen from cubic nanoparticles compared to that of pure ibuprofen, with evidence of a longer half-life and a relative oral bioavailability of 222% (P ibuprofen-loaded cubic nanoparticles provide a promising carrier candidate with an efficient drug delivery for therapeutic treatment. PMID:23468008

  10. Preclinical study of the interference of different nutritional diets on the anti-inflammatory and analgesic actions of etoricoxib

    OpenAIRE

    Bianchetti, Erica S.; Costa Dos Santos, Kelem; Perazzo, Fábio F.; Carvalho, José C. T.

    2010-01-01

    The aim of this research was to evaluate the interference of the association of different types of nutritional diet in the anti-inflammatory and analgesic activities of etoricoxib in in vivo models. The following assays were used: a) Rat paw edema induced by carrageenan; b) Induction of the granulomatous tissue by cotton pellet; c) Dermatitis induced by croton oil; d) Vascular permeability by histamine in rats; e) Writhing test by acetic acid in mice; f) Formalin test in mice and; g) Stress-i...

  11. Comparative study of anti-inflammatory, ulcerogenic and cytotoxic activities of racemate and S-ibuprofen

    Directory of Open Access Journals (Sweden)

    Flavio Henrique Nuevo Benez

    2013-08-01

    Full Text Available Ibuprofen is widely commercialized in racemic form. Although metabolic chiral inversion occurs through the conversion of R(--ibuprofen to S(+-ibuprofen and the latter enantiomer is considered the active form, clinical trials involving the administration of a racemate to S-enantiomer dosage ratio of 1:0.5 have demonstrated that S(+-ibuprofen is as efficacious as the racemic formulation. Moreover, the R(--enantiomer has been implicated in adverse gastrointestinal effects found with the racemic form, but the mechanisms involved in this process are not yet fully understood. The aim of the present study was to evaluate the anti-inflammatory activity of a racemate to S(+-ibuprofen dosage ratio of 1:0.5 using the carrageenan air pouch model of inflammation and determine both ulcerogenic activity and the chiral conversion rate in rats. An in vitro study of the cytotoxicity of racemate and S(+-ibuprofen in gastric cells was also performed. Although the plasma level of S(+-ibuprofen was raised after racemate administration, no significant difference was found in anti-inflammatory activity, as assessed by exudate formation, PGE2 production and leukocyte migration to the air pouches. Fewer gastric lesions were found after S(+-ibuprofen administration, despite the low gastric PGE2 content. In the in vitro study, the racemic compound proved more cytotoxic than S(+-ibuprofen. The present findings suggest that the S-enantiomer of ibuprofen could be considered a therapeutic alternative to minimize gastrointestinal side effects, since the chiral inversion of R(--ibuprofen to S(+-ibuprofen did not result in an improved anti-inflammatory response.

  12. Impact of pore characteristics of silica materials on loading capacity and release behavior of ibuprofen.

    Science.gov (United States)

    Numpilai, Thanapha; Muenmee, Suthaporn; Witoon, Thongthai

    2016-02-01

    Impact of pore characteristics of porous silica supports on loading capacity and release behavior of ibuprofen was investigated. The porous silica materials and ibuprofen-loaded porous silica materials were thoroughly characterized by N2-sorption, thermal gravimetric and derivative weight analyses (TG-DTW), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), transmission electron microscope (TEM) to determine the physical properties of materials, amount of ibuprofen adsorbed and position of ibuprofen. The detailed characterization reveals that the ibuprofen molecules adsorbed inside the mesopores. Increasing the mesopore size from 5nm to 10nm increased the ibuprofen loading from 0.74 to 0.85mmol/g, respectively. Incorporation of macropore into the structure of porous silica materials enhanced the ibuprofen loading capacity of 11.8-20.3%. The ibuprofen-loaded bimodal meso-macroporous silica materials exhibited the highest dissolution of 92wt.% within an hour. The ibuprofen particles deposited on the external surface of the porous silica materials showed a lower dissolution rate than the ibuprofen adsorbed inside the mesopores due to the formation of ibuprofen crystalline. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Mechanistic studies of the metabolic chiral inversion of (R)-ibuprofen in humans

    International Nuclear Information System (INIS)

    Baillie, T.A.; Adams, W.J.; Kaiser, D.G.; Olanoff, L.S.; Halstead, G.W.; Harpootlian, H.; Van Giessen, G.J.

    1989-01-01

    The metabolic chiral inversion of R-(-)-ibuprofen has been studied in human subjects by means of specific deuterium labeling and stereoselective gas chromatography-mass spectrometry methodology. After simultaneous p.o. administration of a mixture of R-(-)-ibuprofen (300 mg) and R-(-)-[3,3,3-2H3]ibuprofen (304 mg) to four adult male volunteers, the enantiomeric composition and deuterium content of the drug in serum, and of the drug and its principal metabolites in urine, were followed over a period of 24 hr. The results of these analyses indicated that: (1) conversion of R-(-)- to S-(+)-ibuprofen takes place with complete retention of deuterium at the beta-methyl (C-3) position; (2) chiral inversion of R-(-)-[2H3]ibuprofen is not subject to a discernible deuterium isotope effect; and (3) replacement of the beta-methyl hydrogen atoms by deuterium has no effect on any of the serum pharmacokinetic parameters for R-(-)- or S-(+)-ibuprofen. These data indicate that the process whereby R-(-)-ibuprofen undergoes metabolic inversion in human subjects does not involve 2,3-dehydroibuprofen as an intermediate, and that the underlying mechanism cannot, therefore, entail a desaturation/reduction sequence

  14. Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans.

    Directory of Open Access Journals (Sweden)

    Kemal Erdem Basaran

    Full Text Available Ventilatory acclimatization to hypoxia is a time-dependent increase in ventilation and the hypoxic ventilatory response (HVR that involves neural plasticity in both carotid body chemoreceptors and brainstem respiratory centers. The mechanisms of such plasticity are not completely understood but recent animal studies show it can be blocked by administering ibuprofen, a nonsteroidal anti-inflammatory drug, during chronic hypoxia. We tested the hypothesis that ibuprofen would also block the increase in HVR with chronic hypoxia in humans in 15 healthy men and women using a double-blind, placebo controlled, cross-over trial. The isocapnic HVR was measured with standard methods in subjects treated with ibuprofen (400 mg every 8 hrs or placebo for 48 hours at sea level and 48 hours at high altitude (3,800 m. Subjects returned to sea level for at least 30 days prior to repeating the protocol with the opposite treatment. Ibuprofen significantly decreased the HVR after acclimatization to high altitude compared to placebo but it did not affect ventilation or arterial O2 saturation breathing ambient air at high altitude. Hence, compensatory responses prevent hypoventilation with decreased isocapnic ventilatory O2-sensitivity from ibuprofen at this altitude. The effect of ibuprofen to decrease the HVR in humans provides the first experimental evidence that a signaling mechanism described for ventilatory acclimatization to hypoxia in animal models also occurs in people. This establishes a foundation for the future experiments to test the potential role of different mechanisms for neural plasticity and ventilatory acclimatization in humans with chronic hypoxemia from lung disease.

  15. Selective degradation of ibuprofen and clofibric acid in two model river biofilm systems.

    Science.gov (United States)

    Winkler, M; Lawrence, J R; Neu, T R

    2001-09-01

    A field survey indicated that the Elbe and Saale Rivers were contaminated with both clofibric acid and ibuprofen. In Elbe River water we could detect the metabolite hydroxy-ibuprofen. Analyses of the city of Saskatoon sewage effluent discharged to the South Saskatchewan river detected clofibric acid but neither ibuprofen nor any metabolite. Laboratory studies indicated that the pharmaceutical ibuprofen was readily degraded in a river biofilm reactor. Two metabolites were detected and identified as hydroxy- and carboxy-ibuprofen. Both metabolites were observed to degrade in the biofilm reactors. However, in human metabolism the metabolite carboxy-ibuprofen appears and degrades second whereas the opposite occurs in biofilm systems. In biofilms the pharmacologically inactive stereoisomere of ibuprofen is degraded predominantly. In contrast, clofibric acid was not biologically degraded during the experimental period of 21 days. Similar results were obtained using biofilms developed using waters from either the South Saskatchewan or Elbe River. In a sterile reactor no losses of ibuprofen were observed. These results suggested that abiotic losses and adsorption played only a minimal role in the fate of the pharmaceuticals in the river biofilm reactors.

  16. Influence of acidic beverage (Coca-Cola) on pharmacokinetics of ibuprofen in healthy rabbits.

    Science.gov (United States)

    Kondal, Amit; Garg, S K

    2003-11-01

    The study was aimed at determining the effect of Coca-Cola on the pharmacokinetics of ibuprofen in rabbits. In a cross-over study, ibuprofen was given orally in a dose of 56 mg/kg, prepared as 0.5% suspension in carboxymethyl cellulose (CMC) and blood samples (1 ml) were drawn at different time intervals from 0-12 hr. After a washout period of 7 days, Coca-Cola in a dose of (5 ml/kg) was administered along with ibuprofen (56 mg/kg) and blood samples were drawn from 0-12 hr. To these rabbits, 5 ml/kg Coca-Cola was administered once daily for another 7 days. On 8th day, Coca-Cola (5 ml/kg) along with ibuprofen (56 mg/kg), prepared as a suspension was administered and blood samples (1 ml each) were drawn at similar time intervals. Plasma was separated and assayed for ibuprofen by HPLC technique and various pharmacokinetic parameters were calculated. The Cmax and AUC0-alpha of ibuprofen were significantly increased after single and multiple doses of Coca-Cola, thereby indicating increased extent of absorption of ibuprofen. The results warrant the reduction of ibuprofen daily dosage, frequency when administered with Coca-Cola.

  17. Morpho-physiological effects of ibuprofen on Scenedesmus rubescens.

    Science.gov (United States)

    Moro, Isabella; Matozzo, Valerio; Piovan, Anna; Moschin, Emanuela; Vecchia, Francesca Dalla

    2014-09-01

    The pollution of aquatic bodies by drugs is an emerging environmental problem, because of their extensive use in animal and human context. Ibuprofen, 2-[4-(2-methylpropyl)phenyl]propanoic acid, is the non-steroidal anti-inflammatory drug mainly present both in wastewater and in rivers and lakes in Europe. Since in literature there is little information about the effects of ibuprofen on microalgae, in this paper we presented the results on the effects of this molecule at different concentrations (62.5μgL(-1), 250μgL(-1) and 1000μgL(-1)) on cultures of the freshwater microalga Scenedesmus rubescens (P.J.L. Dangeard) E. Kesslet et al. Ibuprofen effects on the alga were assayed at first through analyses of the growth curve. Moreover, analyses of cell morphology, ultrastructure, and photosynthetic pigments were additionally performed. The first negative effect of the drug was on the microalga growth, suggesting a drug action dose-dependent mechanism type, more evident at the concentration of 1000μgL(-1) ibuprofen and in the last phase of the growth curve. In support of this, following ibuprofen exposure, the cells exhibited morphological and ultrastructural alterations, mainly consisting in large cytoplasmic inclusions, probably of lipids and/or carotenoids. The decrease of chlorophyll amounts and, on the contrary, the increase of carotenoids were correlated with a stressful condition induced by drug. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Differential renal adverse effects of ibuprofen and indomethacin in preterm infants: a review

    Directory of Open Access Journals (Sweden)

    Pacifici GM

    2014-07-01

    Full Text Available Gian Maria Pacifici Medical School, Department of Translational Research and New Technologies in Medicine and Surgery, Section of Pharmacology, University of Pisa, Pisa, Italy Objective: The objective of this study was to evaluate the extent of renal adverse effects caused by ibuprofen or indomethacin in order to choose the safer drug to administer to preterm infants. Methods: The following three parameters of renal function were taken into consideration: 1 the urine output; 2 the serum creatinine concentration; and 3 the frequency of oliguria. The bibliographic search was performed using PubMed and Embase databases as search engines. Results: Urine output ranged from 3.5±1.2 to 4.0±1.4 mL/kg/h after ibuprofen treatment, and from 2.8±1.1 to 3.6±1.4 mL/kg/h after indomethacin treatment. The values for ibuprofen are significantly (P<0.05 higher than those for indomethacin. The serum creatinine concentrations ranged from 0.98±0.24 to 1.48±0.2 mg/dL after ibuprofen treatment, and from 1.06±0.24 and 2.03±2.10 mg/dL after indomethacin treatment. The values for ibuprofen are significantly (P<0.05 lower than those for indomethacin. The frequency of oliguria ranged from 1.0% to 9.6% (ibuprofen and from 14.8% to 40.0% (indomethacin, and was significantly lower following ibuprofen than indomethacin administration. In infants with body weight lower than 1,000 g, oliguria appeared in 5% (ibuprofen and 40% (indomethacin; P=0.02. Conclusion: Indomethacin is associated with more severe renal adverse effects than ibuprofen. Ibuprofen is less nephrotoxic than indomethacin and should be used to treat patent ductus arteriosus in preterm infants. Immaturity increases the frequency of adverse effects of indomethacin. Keywords: ibuprofen, indomethacin, patent-ductus-arteriosus, renal-side-effects

  19. Controlled release of ibuprofen using Mg Al LDH nano carrier

    Science.gov (United States)

    Dasgupta, Sudip

    2017-08-01

    In the present study, NSAID (non-steroidal anti-inflammatory drugs) such as ibuprofen in anionic form has been intercalated in-situ into the interlayer space of Mg Al LDH nanoparticle during co-precipitation of hydroxides. LDH nanohybrids are characterized by XRD, FTIR and UV spectroscopy. Mg1-xAlx(NO3)x(OH)2.nH2O nanoparticles were synthesized using co-precipitation method from an aqueous solution of Mg(NO3)2.6H2O and Al(NO3)3.9H2O. Ibuprofen was intercalated in inter layer space of Mg-Al LDH during coprecipitation of drug LDH conjugate in nitrogen atmosphere. The nanopowders synthesised were in the size range between 25 to 90 nm with an average particle size of 55 nm. XRD analysis proved that there is an increase in d003 spacing from 7.89 Å for pristine LDH to 14.71 Å for ibuprofen intercalated LDH due to the intercalation of bigger ibuprofen molecule in the interlayer space of LDH. FTIR analysis showed hydroxyl and carbonyl stretching of ibuprofen in LDH-IBU sample confirming the intercalation of ibuprofen in the interlayer structure of LDH. The drug release study in phosphate buffer solution at pH 7.4 using UV-Vis spectroscopy demonstrated that 50 % drug molecules were released in 15 hours and more than 85 % release was achieved after 36 hours.

  20. Ibuprofen Ameliorates Fatigue- and Depressive-like Behavior in Tumor-bearing Mice

    Science.gov (United States)

    Norden, Diana M.; McCarthy, Donna O.; Bicer, Sabahattin; Devine, Raymond; Reiser, Peter J.; Godbout, Jonathan P.; Wold, Loren E.

    2015-01-01

    Aims Cancer-related fatigue (CRF) is often accompanied by depressed mood, both of which reduce functional status and quality of life. Research suggests that increased expression of pro-inflammatory cytokines are associated with skeletal muscle wasting and depressive- and fatigue- like behaviors in rodents and cancer patients. We have previously shown that treatment with ibuprofen, a nonsteroidal anti-inflammatory drug, preserved muscle mass in tumor-bearing mice. Therefore, the purpose of the present study was to determine the behavioral effects of ibuprofen in a mouse model of CRF. Main Methods Mice were injected with colon-26 adenocarcinoma cells and treated with ibuprofen (10mg/kg) in the drinking water. Depressive-like behavior was determined using the forced swim test (FST). Fatigue-like behaviors were determined using voluntary wheel running activity (VWRA) and grip strength. The hippocampus, gastrocnemius muscle, and serum were collected for cytokine analysis. Key Findings Tumor-bearing mice showed depressive-like behavior in the FST, which was not observed in mice treated with ibuprofen. VWRA and grip strength declined in tumor-bearing mice, and ibuprofen attenuated this decline. Tumor-bearing mice had decreased gastrocnemius muscle mass and increased expression of IL-6, MAFBx and MuRF mRNA, biomarkers of protein degradation, in the muscle. Expression of IL-1β and IL-6 was also increased in the hippocampus. Treatment with ibuprofen improved muscle mass and reduced cytokine expression in both the muscle and hippocampus of tumor-bearing mice. Significance Ibuprofen treatment reduced skeletal muscle wasting, inflammation in the brain, and fatigue- and depressive-like behavior in tumor-bearing mice. Therefore, ibuprofen warrants evaluation as an adjuvant treatment for CRF. PMID:26498217

  1. Celecoxib Down-Regulates the Hypoxia-Induced Expression of HIF-1α and VEGF Through the PI3K/AKT Pathway in Retinal Pigment Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Yi-zhou Sun

    2017-12-01

    Full Text Available Background/Aims: The goal of this study was to detect the expression of hypoxia-inducible factor 1α (HIF-1α and vascular endothelial growth factor (VEGF in human retinal pigmented epithelial (RPE cells treated with celecoxib, a selective cyclooxygenase-2 (COX-2 inhibitor, under hypoxic and normoxic conditions and to explore the signaling mechanism involved in regulating the hypoxia-induced expression of HIF-1α and VEGF in RPE cells. Methods: D407 cells were cultured in normoxic or hypoxic conditions, with or without celecoxib or a PI3K inhibitor (LY294002. The anti-proliferative effect of celecoxib was assessed using the MTT assay. RT-PCR, Western blotting and ELISA were performed to detect the levels of PI3K, phosphorylated AKT (p-AKT, HIF-1α, VEGF and COX-2. Results: Celecoxib inhibited the proliferation of RPE cells in a dose-dependent manner. Celecoxib suppressed the expression of VEGF at both the mRNA and protein levels and decreased HIF-1α protein expression. HIF-1α activation was regulated by the PI3K/AKT pathway. The celecoxib-induced down-regulation of HIF-1α and VEGF required the suppression of the hypoxia-induced PI3K/AKT pathway. However, the down-regulation of COX-2 did not occur in cells treated with celecoxib. Conclusions: The antiangiogenic effects of celecoxib in RPE cells under hypoxic conditions resulted from the inhibition of HIF-1α and VEGF expression, which may be partly mediated by a COX-2-independent, PI3K/AKT-dependent pathway.

  2. Cutaneous irritancy of an ibuprofen medicated plaster in healthy volunteers.

    Science.gov (United States)

    Maganji, Manisha; Connolly, Mark P; Bhatt, Aomesh

    2018-04-01

    To assess the irritation and contact sensitization potential of a 200 mg ibuprofen medicated plaster. This double-blind, phase-1 placebo controlled study had two phases; the induction phase to evaluate the irritant potential of continuous application of the plaster, and the challenge phase to assess contact sensitivity (allergy). The cumulative irritancy potential was evaluated using an adaptation of the Shelanski method. Healthy adults (≥18 years of age) (N = 210) were treated simultaneously with one ibuprofen medicated and one placebo plaster applied in a randomized fashion to either the left or right side of the lower back. During the induction phase, plasters were applied on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 and the final plaster removed on Day 22. At each scheduled visit plasters and applications sites were assessed for degree of adhesion and skin irritation (score of 1 = no irritation to 7 = strong reaction spreading beyond test sites), respectively. The challenge phase followed a two-week washout period. A plaster was applied on Day 36 for 48 h and assessment occurred on Days 38, 39, and 40. The mean cumulative irritation score during the induction phase was lower for the ibuprofen medicated plaster than the placebo plaster (0.32 vs. 1.23, respectively). Three (1.4%) subjects experience a dermal reaction of grade ≥3 for the ibuprofen medicated plaster compared with 27 (12.7%) for the placebo plaster. Following challenge with ibuprofen or placebo plasters, 12 subjects (6.2%) with the ibuprofen medicated plaster and four (2.2%) with the placebo plaster had skin reaction of assessment grade higher than the induction phase. One subject for the ibuprofen and two for the placebo plaster had reactions with grade >2. No subjects showed an increase in sensitization on Day 39 or 40 compared with Day 38. The findings indicate that the both the irritancy and contact sensitization of the ibuprofen medicated plaster is acceptable.

  3. Growth, spectral and thermal studies of ibuprofen crystals

    Energy Technology Data Exchange (ETDEWEB)

    Ramukutty, S.; Ramachandran, E. [Department of Physics, Thiruvalluvar College, Papanasam (India)

    2012-01-15

    RS -Ibuprofen was crystallized for the first time in silica gel under suitable pH conditions by reduction of solubility method. The grown crystals were characterized by single crystal X-ray diffraction and density measurement. The functional groups present in the crystal were identified using Fourier transform infrared spectroscopy. Optical bandgap energy of ibuprofen was estimated as 3.19(3) eV from UV-Vis spectrum. Thermogravimetric analysis revealed that ibuprofen is thermally stable upto 102.9 C and the initial loss of mass was due to evaporation only. Morphological study showed that the growth is prominent along b-axis and the prominent face is {l_brace}100{r_brace}. (copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  4. Ibuprofen in paediatrics: pharmacology, prescribing and controversies.

    Science.gov (United States)

    Moriarty, Camilla; Carroll, Will

    2016-12-01

    Ibuprofen, a propionic acid derivative, is a non-steroidal anti-inflammatory drug. The oral formulation is widely used in paediatric practice and after paracetamol it is one of the most common drugs prescribed for children in hospital. The treatment of fever with antipyretics such as ibuprofen is controversial as fever is the normal response of the body to infection and unless the child becomes distressed or symptomatic, fever alone should not be routinely treated. Combined treatment with paracetamol and ibuprofen is commonly undertaken but almost certainly is not helpful. This article aims to describe the indications and mode of action of the drug, outline its pharmacokinetics and highlight the important key messages regarding its use in clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. Physico-mechanical and dissolution behaviours of ibuprofen crystals crystallized in the presence of various additives

    Directory of Open Access Journals (Sweden)

    A Nokhodchi

    2010-06-01

    Full Text Available "n  "n Background and the purpose of the study: The success of any direct-tableting procedure is strongly affected by the quality of the crystals used in the process. Ibuprofen is a poorly compactible drug with a high tendency for capping. In order to use ibuprofen in direct compression formulations, physico-mechanical properties of ibuprofen should be improved considerably. The aim of the present investigation was to employ crystallization techniques in order to improve the physico-mechanical properties of ibuprofen for direct compression. "nMethods:The experimental methods involved the preparation of ibuprofen crystals by solvent change technique. Ibuprofen was dissolved in ethanol and crystallized out with water in the absence or presence of various hydrophilic additives (PEG 6000, 8000, Brij 98P and polyvinyl alcohol 22000, PVA 22000 with different concentrations. The physico-mechanical properties of the ibuprofen crystals were studied in terms of flow, density, tensile strength and dissolution behaviour. Morphology of ibuprofen crystals was studied by scanning electron microscopic (SEM. Solid state of the recrystallized particles was also investigated using differential scanning calorimeter (DSC and FT-IR. "nResults:Ibuprofen samples crystallized in the presence of PEG 6000 and 8000 and PVA showed remarkable increase in the tensile strengths of the directly compressed tablets, while some other additives, i.e. Brij 98P did not produce improved ibuprofen crystals. Ibuprofen powders made from particles obtained in the presence of PVA and Brij 98P showed similar dissolution profiles to the commercial ibuprofen particles. DSC and FT-IR results ruled out any significant interaction between ibuprofen and additives except for the samples crystallized in the presence of PEG 8000. Conclusion:The crystal habit of ibuprofen can be altered successfully by the crystallization technique which was developed in this study. The crystals developed in the

  6. Synthesis of carbon-13 labeled ibuprofen

    International Nuclear Information System (INIS)

    Hsi, R.S.P.; Stelzer, L.S.; Stolle, W.T.

    1989-01-01

    This report describes the synthesis of 2-[4-(2-methyl)propyl-phenyl]propionic acid (ibuprofen) labeled with carbon-13 either at the terminal methyl carbons, or at the methine carbon of the isobutyl side chain. The synthetic route involves the removal of the isopropyl group in the isobutyl side-chain of ibuprofen via 2-[4-(2-methyl-1-propenyl)phenyl]propionic acid, followed by restoration of the isopropyl group with a Wittig reaction, using appropriate carbon-13 labeled acetone as the precursor of the isopropyl group. Interesting NMR coupling data attributable to phosphorous and carbon-13 are presented in the experimental section. (author)

  7. Pharmacokinetics of acetaminophen and ibuprofen when coadministered with telmisartan in healthy volunteers.

    Science.gov (United States)

    Stangier, J; Su, C A; Fraunhofer, A; Tetzloff, W

    2000-12-01

    Two open-label, two-way, crossover studies were performed to assess any pharmacokinetic interaction of telmisartan with either acetaminophen or ibuprofen. Healthy male adult volunteers (n = 12) received a single oral dose of acetaminophen 1 g alone and with oral telmisartan 120 mg in one study. Oral ibuprofen 400 mg three times daily with and without oral once-daily telmisartan 120 mg was given for 7 days in the other study conducted in 6 males and 6 females. In both studies, there was a washout period of > or = 13 days between single and combination medication administration. The primary end points Cmax and AUC were compared between combination (acetaminophen or ibuprofen + telmisartan) and single-agent medication (acetaminophen or ibuprofen). Pharmacokinetic drug interaction was assessed by analysis of variance (ANOVA) and calculation of 90% confidence intervals (CI) for treatment ratios using log-transformed parameters. Bioequivalence (i.e., lack of interaction) was concluded if the 90% CI of the ratios for both Cmax and AUC were within the acceptance limit of 0.80 to 1.25. Geometric mean Cmax values for acetaminophen and R-(-)- and S-(+)-ibuprofen enantiomers were similar with and without telmisartan coadministration (12.6 micrograms/mL vs. 14.1 micrograms/mL; 17.3 micrograms/mL vs. 16.7 micrograms/mL; 19.4 micrograms/mL vs. 19.5 micrograms/mL, respectively), and values for R-(-)- as well as S-(+)-ibuprofen were bioequivalent. Geometric mean AUC values for acetaminophen and R-(-)- and S-(+)-ibuprofen were also bioequivalent with and without telmisartan. The distribution and elimination parameters of both acetaminophen and ibuprofen were comparable in the presence or absence of telmisartan. The concomitant and single-agent medications were all well tolerated. In conclusion, the long half-life and excellent safety profile of telmisartan were unaffected by concurrent acetaminophen or ibuprofen medication; thus, once-daily dosing of telmisartan can be maintained

  8. Ibuprofen Differentially Affects Supraspinatus Muscle and Tendon Adaptations to Exercise in a Rat Model

    Science.gov (United States)

    Rooney, Sarah Ilkhanipour; Baskin, Rachel; Torino, Daniel J.; Vafa, Rameen P.; Khandekar, Pooja S.; Kuntz, Andrew F.; Soslowsky, Louis J.

    2017-01-01

    Background Previous studies have shown that ibuprofen is detrimental to tissue healing following acute injury; however, the effects of ibuprofen when combined with non-injurious exercise are debated. Hypothesis We hypothesized that administration of ibuprofen to rats undergoing a non-injurious treadmill exercise protocol would abolish the beneficial adaptations found with exercise but have no effect on sedentary muscle and tendon properties. Study Design Controlled laboratory study Methods Rats were divided into exercise or cage activity (sedentary) groups and acute (a single bout of exercise followed by 24 hours of rest) and chronic (2 or 8 weeks of repeated exercise) time points. Half of the rats received ibuprofen to investigate the effects of this drug over time when combined with different activity levels (exercise and sedentary). Supraspinatus tendons were used for mechanical testing and histology (organization, cell shape, cellularity), and supraspinatus muscles were used for morphological (fiber CSA, centrally nucleated fibers) and fiber type analysis. Results Chronic intake of ibuprofen did not impair supraspinatus tendon organization or mechanical adaptations (stiffness, modulus, max load, max stress, dynamic modulus, or viscoelastic properties) to exercise. Tendon mechanical properties were not diminished and in some instances increased with ibuprofen. In contrast, total supraspinatus muscle fiber cross-sectional area decreased with ibuprofen at chronic time points, and some fiber type-specific changes were detected. Conclusions Chronic administration of ibuprofen does not impair supraspinatus tendon mechanical properties in a rat model of exercise but does decrease supraspinatus muscle fiber cross-sectional area. Clinically, these findings suggest that ibuprofen does not detrimentally affect regulation of supraspinatus tendon adaptions to exercise but does decrease muscle growth. Individuals should be advised on the risk of decreased muscle hypertrophy

  9. Pain from copper intrauterine device insertion: randomized trial of prophylactic ibuprofen.

    Science.gov (United States)

    Hubacher, David; Reyes, Veronica; Lillo, Sonia; Zepeda, Ana; Chen, Pai-Lien; Croxatto, Horacio

    2006-11-01

    This study was undertaken to determine whether 400 mg of prophylactic ibuprofen can alleviate pain from insertion of an intrauterine device (IUD) and to measure level of pain with improved techniques. We conducted a randomized, double-blind, placebo-controlled trial of 2019 first-time IUD users: 1008 women received placebo and 1011 women received 400 mg of ibuprofen. Participants took the single tablet at least 45 minutes before IUD insertion. Immediately after insertion, participants recorded level of pain by using a 10-cm visual analog scale, with the value of 10 meaning "worst imaginable pain." Median level of pain was 1.0 for both ibuprofen and placebo participants; rank test statistics confirmed no difference. Some subgroups of women experienced higher pain (eg, nulliparous women), but ibuprofen still had no important impact on level of pain. Even among first-time users, pain from IUD insertion is generally low. Prophylactic ibuprofen as used in this protocol does not reduce IUD insertion pain.

  10. Effects of humidity and surfaces on the melt crystallization of ibuprofen.

    Science.gov (United States)

    Lee, Dong-Joo; Lee, Suyang; Kim, Il Won

    2012-01-01

    Melt crystallization of ibuprofen was studied to understand the effects of humidity and surfaces. The molecular self-assembly during the amorphous-to-crystal transformation was examined in terms of the nucleation and growth of the crystals. The crystallization was on Al, Au, and self-assembled monolayers with -CH(3), -OH, and -COOH functional groups. Effects of the humidity were studied at room temperature (18-20 °C) with relative humidity 33%, 75%, and 100%. Effects of the surfaces were observed at -20 °C (relative humidity 36%) to enable close monitoring with slower crystal growth. The nucleation time of ibuprofen was faster at high humidity conditions probably due to the local formation of the unfavorable ibuprofen melt/water interface. The crystal morphologies of ibuprofen were governed by the nature of the surfaces, and they could be associated with the growth kinetics by the Avrami equation. The current study demonstrated the effective control of the melt crystallization of ibuprofen through the melt/atmosphere and melt/surface interfaces.

  11. The selective Cox-2 inhibitor Celecoxib suppresses angiogenesis and growth of secondary bone tumors: An intravital microscopy study in mice

    International Nuclear Information System (INIS)

    Klenke, Frank Michael; Gebhard, Martha-Maria; Ewerbeck, Volker; Abdollahi, Amir; Huber, Peter E; Sckell, Axel

    2006-01-01

    The inhibition of angiogenesis is a promising strategy for the treatment of malignant primary and secondary tumors in addition to established therapies such as surgery, chemotherapy, and radiation. There is strong experimental evidence in primary tumors that Cyclooxygenase-2 (Cox-2) inhibition is a potent mechanism to reduce angiogenesis. For bone metastases which occur in up to 85% of the most frequent malignant primary tumors, the effects of Cox-2 inhibition on angiogenesis and tumor growth remain still unclear. Therefore, the aim of this study was to investigate the effects of Celecoxib, a selective Cox-2 inhibitor, on angiogenesis, microcirculation and growth of secondary bone tumors. In 10 male severe combined immunodeficient (SCID) mice, pieces of A549 lung carcinomas were implanted into a newly developed cranial window preparation where the calvaria serves as the site for orthotopic implantation of the tumors. From day 8 after tumor implantation, five animals (Celecoxib) were treated daily with Celecoxib (30 mg/kg body weight, s.c.), and five animals (Control) with the equivalent amount of the CMC-based vehicle. Angiogenesis, microcirculation, and growth of A549 tumors were analyzed by means of intravital microscopy. Apoptosis was quantified using the TUNEL assay. Treatment with Celecoxib reduced both microvessel density and tumor growth. TUNEL reaction showed an increase in apoptotic cell death of tumor cells after treatment with Celecoxib as compared to Controls. Celecoxib is a potent inhibitor of tumor growth of secondary bone tumors in vivo which can be explained by its anti-angiogenic and pro-apoptotic effects. The results indicate that a combination of established therapy regimes with Cox-2 inhibition represents a possible application for the treatment of bone metastases

  12. SIMULTANEOUS DETERMINATION OF PARACETAMOL AND IBUPROFENE MIXTURES BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

    Directory of Open Access Journals (Sweden)

    Sophi Damayanti

    2010-06-01

    Full Text Available Analytical method for the determination of paracetamol and ibuprofene mixtures has been developed by High Performance Liquid Chromatography using C-18 column and acetinitrile - phosphate buffer pH = 4.5 (75:25 containing 0.075% sodium hexanesulfunate as a mobile phase. The detector was set at 215 nm. Using such conditions, retention time for paracetamol and ibuprofen was 4.89 and 7.11 min, respectively. The recovery for paracetamol and ibuprofen was found to be 101.07± 0.73% and 102.02 ± 1.58%, respectively. The detector limits of the method was 1.30 and 1.60 μg/mL with the relative standard deviation (RSD 0.74 and 1.52% for paracetamol and ibuprofen, respectively.   Keywords: paracetamol, ibuprofen, multi-component, validation, HPLC.

  13. Repurposing of Aspirin and Ibuprofen as Candidate Anti-Cryptococcus Drugs

    Science.gov (United States)

    Ogundeji, Adepemi O.; Pohl, Carolina H.

    2016-01-01

    The usage of fluconazole and amphotericin B in clinical settings is often limited by, among other things, drug resistance development and undesired side effects. Thus, there is a constant need to find new drugs to better manage fungal infections. Toward this end, the study described in this paper considered the repurposing of aspirin (acetylsalicylic acid) and ibuprofen as alternative drugs to control the growth of cryptococcal cells. In vitro susceptibility tests, including a checkerboard assay, were performed to assess the response of Cryptococcus neoformans and Cryptococcus gattii to the above-mentioned anti-inflammatory drugs. Next, the capacity of these two drugs to induce stress as well as their mode of action in the killing of cryptococcal cells was determined. The studied fungal strains revealed a response to both aspirin and ibuprofen that was dose dependent, with ibuprofen exerting greater antimicrobial action. More importantly, the MICs of these drugs did not negatively (i) affect growth or (ii) impair the functioning of macrophages; rather, they enhanced the ability of these immune cells to phagocytose cryptococcal cells. Ibuprofen was also shown to act in synergy with fluconazole and amphotericin B. The treatment of cryptococcal cells with aspirin or ibuprofen led to stress induction via activation of the high-osmolarity glycerol (HOG) pathway, and cell death was eventually achieved through reactive oxygen species (ROS)-mediated membrane damage. The presented data highlight the potential clinical application of aspirin and ibuprofen as candidate anti-Cryptococcus drugs. PMID:27246782

  14. Dose-dependent effects of celecoxib on CB-1 agonist-induced antinociception in the mice

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Zarrindast

    2009-04-01

    Full Text Available "nObjective: Endocannabinoid produce analgesia that is comparable which of opioids. The mechanism of antinociceptive effects of (∆ - 9 tetrahydrocannabinol (THC is suggested to be through cyclooxygenase (COX pathway. In the present work, the effect of two extreme dose ranges of celecoxib (mg/kg and ng/kg, a cyclooxygenase-2 (COX-2 antagonist, on arachidonylcyclopropylamide (ACPA, a selective CB1 agonist induced antinociception in mice was examined. "nMethods: We have investigated the interaction between celecoxib, at the doses of mg/kg (50, 100, 200 and 400 i.p.  and ultra low dose (ULD (25 and 50 ng/kg, i.p., on the antinociceptive effect of intracerebroventricular (i.c.v. administration of ACPA (0.004, 0.0625 and 1 μg/mice, using formalin test in mice. "nResults: I.C.V. administration of ACPA induced antinociception. Intraperitoneal administration of celecoxib (mg/kg and its ULD (ng/kg attenuated and potentiated, ACPA antinociceptive effects, respectively. "nConclusion: It is concluded that the mg/kg doses of COX-2 antagonist showed opposite effects compare to the ultra-low dose of the drug.

  15. Penetration and pharmacokinetics of non-steroidal anti-inflammatory drugs in rat prostate tissue.

    Science.gov (United States)

    Yellepeddi, Venkata K; Radhakrishnan, Jayashree; Radhakrishnan, Rajan

    2018-02-01

    Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) involves inflammation of the prostate and affects the quality of life of men of all ages. It is well reported in clinical studies that the treatment for CP/CPPS using nonsteroidal anti-inflammatory drugs (NSAIDs) produced favorable outcomes. However, currently, there are no guidelines on choice of the NSAIDs for the treatment of CP/CPPS. Therefore, in the current research study, we evaluated the prostate tissue penetration of four NSAIDs in rats to provide guidance on choice of NSAIDs for the treatment of CP/CPPS. Male Sprague-Dawley rats were administered orally with four NSAIDs viz. celecoxib, diclofenac, ibuprofen, and naproxen at 500 mg/kg dose. The animals were then sacrificed at various time points, and their prostate tissues were harvested. The NSAIDs were then extracted from the prostate tissues using liquid extraction technique, and their concentration in prostate tissue was quantified using high-performance liquid chromatography (HPLC). The prostate tissue penetration and related pharmacokinetic parameters were evaluated by non-compartmental analysis. The HPLC method for quantifying NSAIDs in prostate tissue resulted in single, sharp peaks without any interference and all validation parameters were within limits. Celecoxib showed the highest area under the curve (AUC) [146.50 ± 2.75 μg/mL*h] of all NSAID's. A two-factor analysis of variance (ANOVA) with replication indicated an overall statistically significant difference in the pharmacokinetic parameters for celecoxib, diclofenac, ibuprofen, and naproxen. This study for the first time reported the relative prostate tissue penetration of four NSAIDs. The pharmacokinetic data indicated that celecoxib has the highest penetration and retention in rat prostate tissues. Therefore, celecoxib may be considered as a better choice for the treatment CP/CPPS involving NSAIDs. © 2017 Wiley Periodicals, Inc.

  16. Controlled release of ibuprofen by meso–macroporous silica

    Energy Technology Data Exchange (ETDEWEB)

    Santamaría, E., E-mail: esthersantamaria@ub.edu; Maestro, A.; Porras, M.; Gutiérrez, J.M.; González, C.

    2014-02-15

    Structured meso–macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (EO{sub 19}PO{sub 39}EO{sub 19}) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption–desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso–macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system. - Graphical abstract: Ibuprofen release profiles for the materials obtained from samples P84{sub m}eso (black diamonds), P84{sub 2}0% (white squares), P84{sub 5

  17. Controlled release of ibuprofen by meso–macroporous silica

    International Nuclear Information System (INIS)

    Santamaría, E.; Maestro, A.; Porras, M.; Gutiérrez, J.M.; González, C.

    2014-01-01

    Structured meso–macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (EO 19 PO 39 EO 19 ) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption–desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso–macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system. - Graphical abstract: Ibuprofen release profiles for the materials obtained from samples P84 m eso (black diamonds), P84 2 0% (white squares), P84 5 0% (black triangles), P84 7

  18. Effect of racemic ibuprofen dose on the magnitude and duration of platelet cyclo-oxygenase inhibition: relationship between inhibition of thromboxane production and the plasma unbound concentration of S(+)-ibuprofen.

    Science.gov (United States)

    Evans, A M; Nation, R L; Sansom, L N; Bochner, F; Somogyi, A A

    1991-02-01

    1. Four healthy male subjects received racemic ibuprofen (200, 400, 800 and 1200 mg), orally, on four occasions, 2 weeks apart, according to a four-way Latin-square design, in order to investigate the influence of increasing dose of ibuprofen on the magnitude and duration of its antiplatelet effect as well as on the relationship between such effect and drug concentration. 2. The antiplatelet effect of ibuprofen was assessed by measuring the inhibition of platelet thromboxane B2 (TXB2) generation during the controlled clotting of whole blood. The plasma unbound concentration of S(+)-ibuprofen, the enantiomer shown in an in vitro study to be responsible for the inhibitory effect of platelet TXB2 generation, was measured using an enantioselective method. 3. The maximum percentage inhibition of TXB2 generation increased significantly with dose from a mean +/- s.d. of 93.4 +/- 1.2% after the 200 mg dose to 98.8 +/- 0.3% after the 1200 mg dose, and there was an increase with dose in the duration of inhibition of TXB2 generation. The effect of ibuprofen on platelet TXB2 generation was transient and mirrored the time-course of unbound S(+)-ibuprofen in plasma; on all but one of the 16 occasions, serum TXB2 concentrations returned to at least within 10% of the pretreatment concentrations within 24 h of ibuprofen administration. 4. For each subject, the relationship between the percentage inhibition of TXB2 generation and the unbound concentration of S(+)-ibuprofen in plasma was modelled according to a sigmoidal Emax equation. The mean plasma unbound concentration of S(+)-ibuprofen required to inhibit platelet TXB2 generation by 50% (EC50) was 9.8 +/- 1.0 micrograms l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. {beta}-TCP porous pellets as an orthopaedic drug delivery system: ibuprofen/carrier physicochemical interactions

    Energy Technology Data Exchange (ETDEWEB)

    Baradari, Hiba; Damia, Chantal; Dutreih-Colas, Maggy; Champion, Eric; Chulia, Dominique; Viana, Marylene, E-mail: hiva.baradari@etu.unilim.fr [SPCTS-Centre Europeen de la Ceramique, 12 Rue Atlantis, 87068 Limoges CEDEX (France)

    2011-10-15

    Calcium phosphate bone substitute materials can be loaded with active substances for in situ, targeted drug administration. In this study, porous {beta}-TCP pellets were investigated as an anti-inflammatory drug carrier. Porous {beta}-TCP pellets were impregnated with an ethanolic solution of ibuprofen. The effects of contact time and concentration of ibuprofen solution on drug adsorption were studied. The ibuprofen adsorption equilibrium time was found to be one hour. The adsorption isotherms fitted to the Freundlich model, suggesting that the interaction between ibuprofen and {beta}-TCP is weak. The physicochemical characterizations of loaded pellets confirmed that the reversible physisorption of ibuprofen on {beta}-TCP pellets is due to Van der Waals forces, and this property was associated with the 100% ibuprofen release.

  20. β-TCP porous pellets as an orthopaedic drug delivery system: ibuprofen/carrier physicochemical interactions

    International Nuclear Information System (INIS)

    Baradari, Hiba; Damia, Chantal; Dutreih-Colas, Maggy; Champion, Eric; Chulia, Dominique; Viana, Marylene

    2011-01-01

    Calcium phosphate bone substitute materials can be loaded with active substances for in situ, targeted drug administration. In this study, porous β-TCP pellets were investigated as an anti-inflammatory drug carrier. Porous β-TCP pellets were impregnated with an ethanolic solution of ibuprofen. The effects of contact time and concentration of ibuprofen solution on drug adsorption were studied. The ibuprofen adsorption equilibrium time was found to be one hour. The adsorption isotherms fitted to the Freundlich model, suggesting that the interaction between ibuprofen and β-TCP is weak. The physicochemical characterizations of loaded pellets confirmed that the reversible physisorption of ibuprofen on β-TCP pellets is due to Van der Waals forces, and this property was associated with the 100% ibuprofen release.

  1. Ibuprofen pharmacokinetics in preterm infants with patent ductus arteriosus

    NARCIS (Netherlands)

    Van Overmeire, B; Touw, D; Schepens, P J; Kearns, G L; van den Anker, J N

    2001-01-01

    OBJECTIVE: Our objective was to study the pharmacokinetics of ibuprofen in premature infants with patent ductus arteriosus on day 3 and day 5 after birth. METHODS: Ibuprofen was administered on days 3, 4, and 5 by a 15-minute intravenous infusion of 10, 5, and 5 mg/kg, respectively, with the aim of

  2. Cooperative Enhancement of Radiosensitivity After Combined Treatment of 17-(Allylamino)-17-Demethoxygeldanamycin and Celecoxib in Human Lung and Colon Cancer Cell Lines

    Science.gov (United States)

    Kim, Young-Mee

    2012-01-01

    We investigated whether the combined treatment of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), an inhibitor of heat-shock protein 90 (hsp90), and celecoxib, an inhibitor of cyclooxygenase-2, can cooperatively enhance the radiosensitivity of various human cancer cells. Combined treatment with 17-AAG and celecoxib, at clinically relevant concentrations, cooperatively induced radiosensitization in all tested cancer cells, but not in normal cells. Cooperative radiosensitization by the drug combination was also shown in a human tumor xenograft system. We found that ataxia-telangiectasia and rad3-related (ATR) and ataxia-telangiectasia mutated (ATM) are novel client proteins of hsp90. Combined treatment with 17-AAG and celecoxib cooperatively induced downregulation of ATR and ATM. In conclusion, combined treatment with 17-AAG and celecoxib at clinically relevant concentrations may significantly enhance the therapeutic efficacy of ionizing radiation. PMID:21830942

  3. EFFICACY OF IBUPROFEN IN TREATMENT OF PAIN IN CHILDREN: SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED STUDIES

    Directory of Open Access Journals (Sweden)

    R.T. Saygitov

    2010-01-01

    Full Text Available The article presents results of systematic review of data on prophylactic and therapeutic efficacy of ibuprofen. Data search was performed by PubMed database and Google search. 27 publications for analysis were available. Prophylactic efficacy of ibuprofen was studied in 14 studies. Summarizing of the results showed that ibuprofen prevents pain and decreases its following intensity after different surgical or dental operations. There is no significant difference in prophylactic efficacy of single dose ibuprofen and acetaminophen. Therapeutic efficacy of ibuprofen was described in 13 studies. Administration of the drug for pain stopping in children is reasonable. The analgesic effect of ibuprofen compared to placebo was shown in all studies of patients with migraine and diseases of ENT-organs. 5 studies performed in last 5 years showed efficacy of ibuprofen in trauma patients, including children with non-complicated fractures of extremities.Key words: children, pain, ibuprofen, prophylaxis, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(6:52-62

  4. Does ibuprofen treatment in patent ductus arteriosus alter oxygen free radicals in premature infants?

    Science.gov (United States)

    Akar, Melek; Yildirim, Tulin G; Sandal, Gonca; Bozdag, Senol; Erdeve, Omer; Altug, Nahide; Uras, Nurdan; Oguz, Serife S; Dilmen, Ugur

    2017-04-01

    Introduction Ibuprofen is used widely to close patent ductus arteriosus in preterm infants. The anti-inflammatory activity of ibuprofen may also be partly due to its ability to scavenge reactive oxygen species and reactive nitrogen species. We evaluated the interaction between oxidative status and the medical treatment of patent ductus arteriosus with two forms of ibuprofen. Materials and methods This study enrolled newborns of gestational age ⩽32 weeks, birth weight ⩽1500 g, and postnatal age 48-96 hours, who received either intravenous or oral ibuprofen to treat patent ductus arteriosus. Venous blood was sampled before ibuprofen treatment from each patient to determine antioxidant and oxidant concentrations. Secondary samples were collected 24 hours after the end of the treatment. Total oxidant status and total antioxidant capacity were measured using Erel's method. This prospective randomised study enrolled 102 preterm infants with patent ductus arteriosus. The patent ductus arteriosus closure rate was significantly higher in the oral ibuprofen group (84.6 versus 62%) after the first course of treatment (p=0.011). No significant difference was found between the pre- and post-treatment total oxidant status and total antioxidant capacity in the groups. Discussion Ibuprofen treatment does not change the total oxidant status or total antioxidant capacity. We believe that the effect of ibuprofen treatment in inducing ischaemia overcomes the scavenging effect of ibuprofen.

  5. Etoricoxib selective sensor based on uracil-5,6-diamino-2-thio hydrochloride as neutral carrier for potentiometric analysis in pharmaceutical preparations

    Directory of Open Access Journals (Sweden)

    Salwa Fares Rassi

    2016-06-01

    Full Text Available A construction and electrochemical behavior of novel potentiometric membrane sensor responsive to the etoricoxib was described. The sensor was based on the ion-pair complex of etoricoxib (ET with Uracil-5,6-diamino-2-thio hydrochloride UDTH (ET-UDTH as exchange sites in a PVC matrix with different plasticizers dibutylphthalate (DBP (electrode B tri-n-butylphosphate (TBP (electrode C, and dioctylphthalate (DOP (electrode A. The electrodes exhibited near-Nernstian response for ET-UDTH over the concentration range 0.051-40.042 mM. The electrode offered significant advantages including long lifetime (about 2 months, excellent stability and reproducibility, good response time (10-25 s, and wide pH working range (pH 5-12. Selectivity coefficients of ET related to a number of interfering cation and some organic compounds were investigated, and there were negligible interference caused by most of the investigated species. The direct determination of 0.5-10 mM of ET showed an average recovery of 99.03-101.75% and a mean relative standard deviation 0.40-1.88. The results were obtained by determination of ET in tablets using the proposed electrodes which were comparable favorably with those obtained by spectrophotometric method

  6. Expression Patterns of Cancer Stem Cell Markers During Specific Celecoxib Therapy in Multistep Rat Colon Carcinogenesis Bioassays.

    Science.gov (United States)

    Salim, Elsayed I; Hegazi, Mona M; Kang, Jin Seok; Helmy, Hager M

    2016-01-01

    The purpose of this study was to investigate the role of colon cancer stem cells (CSCs) during chemicallyinduced rat multi-step colon carcinogenesis with or without the treatment with a specific cyclooxygenase-2 inhibitor drug (celecoxib). Two experiments were performed, the first, a short term 12 week colon carcinogenesis bioassay in which only surrogate markers for colon cancer, aberrant crypt foci (ACF) lesions, were formed. The other experiment was a medium term colon cancer rat assay in which tumors had developed after 32 weeks. Treatment with celecoxib lowered the numbers of ACF, as well as the tumor volumes and multiplicities after 32 weeks. Immunohistochemical proliferating cell nuclear antigen (PCNA) labeling indexes LI (%) were downregulated after treatment by celecoxib. Also different cell surface antigens known to associate with CSCs such as the epithelial cell adhesion molecule (EpCAM), CD44 and CD133 were compared between the two experiments and showed differential expression patterns depending on the stage of carcinogenesis and treatment with celecoxib. Flow cytometric analysis demonstrated that the numbers of CD133 cells were increased in the colonic epithelium after 12 weeks while those of CD44 but not CD133 cells were increased after 32 weeks. Moreover, aldehyde dehydrogenase-1 activity levels in the colonic epithelium (a known CSC marker) detected by ELISA assay were found down-regulated after 12 weeks, but were up-regulated after 32 weeks. The data have also shown that the protective effect of celecoxib on these specific markers and populations of CSCs and on other molecular processes such as apoptosis targeted by this drug may vary depending on the genetic and phenotypic stages of carcinogenesis. Therefore, uncovering these distinction roles of CSCs during different phases of carcinogenesis and during specific treatment could be useful for targeted therapy.

  7. Celecoxib does not significantly delay bone healing in a rat femoral osteotomy model: a bone histomorphometry study

    Directory of Open Access Journals (Sweden)

    Iwamoto J

    2011-12-01

    Full Text Available Jun Iwamoto1, Azusa Seki2, Yoshihiro Sato3, Hideo Matsumoto11Institute for Integrated Sports Medicine, Keio University School of Medicine, Tokyo, Japan; 2Hamri Co, Ltd, Tokyo, Japan; 3Department of Neurology, Mitate Hospital, Fukuoka, JapanBackground and objective: The objective of the present study was to determine whether celecoxib, a cyclo-oxygenase-2 inhibitor, would delay bone healing in a rat femoral osteotomy model by examining bone histomorphometry parameters.Methods: Twenty-one 6-week-old female Sprague-Dawley rats underwent a unilateral osteotomy of the femoral diaphysis followed by intramedullary wire fixation; the rats were then divided into three groups: the vehicle administration group (control, n = 8, the vitamin K2 administration (menatetrenone 30 mg/kg orally, five times a week group (positive control, n = 5, and the celecoxib administration (4 mg/kg orally, five times a week group (n = 8. After 6 weeks of treatment, the wires were removed, and a bone histomorphometric analysis was performed on the bone tissue inside the callus. The lamellar area relative to the bone area was significantly higher and the total area and woven area relative to the bone area were significantly lower in the vitamin K2 group than in the vehicle group. However, none of the structural parameters, such as the callus and bone area relative to the total area, lamellar and woven areas relative to the bone area, or the formative and resorptive parameters such as osteoclast surface, number of osteoclasts, osteoblast surface, osteoid surface, eroded surface, and bone formation rate per bone surface differed significantly between the vehicle and celecoxib groups.Conclusion: The present study implies that celecoxib may not significantly delay bone healing in a rat femoral osteotomy model based on the results of a bone histomorphometric analysis.Keywords: femoral osteotomy, bone healing, callus, rat, celecoxib

  8. Formulation and in vitro evaluation of ibuprofen-loaded poly(D,L ...

    African Journals Online (AJOL)

    co-glycolide) (PLGA) microparticles. Methods: Ibuprofen-loaded microparticles containing PLGA were formulated using a emulsification/solvent evaporation method. Various concentrations of ibuprofen (200, 300, 400 and 0 mg) were loaded ...

  9. Dose-dependent reduction of 3,2'-dimethyl-4-aminobiphenyl-derived DNA adducts in colon and liver of rats administered celecoxib

    International Nuclear Information System (INIS)

    Ravoori, Srivani; Feng Yi; Neale, Jason R.; Jeyabalan, Jeyaprakash; Srinivasan, Cidambi; Hein, David W.; Gupta, Ramesh C.

    2008-01-01

    Colon cancer is second leading cause of cancer-related deaths in Western countries. Diet and smoking, which contain aromatic and heterocyclic amines, are major risk factors for colon cancer. Colorectal cancers have a natural history of long latency and therefore provide ample opportunities for effective chemoprevention. 3,2'-Dimethyl-4-aminobiphenyl (DMABP) is an experimental aromatic amine that causes cancer in rat colon and serves as an experimental model for arylamine and heterocyclic amine mutagens derived from diet and smoking. In this study, we investigated the effects of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor on DMABP-induced DNA adduct formation in rat liver and colon. Male F-344 rats (5-week old) were provided free access to modified AIN-76A rat chow containing 0 (control), 500, 1000, or 1500 ppm celecoxib. Two weeks later, the rats received a subcutaneous injection of 100 mg/kg DMABP in peanut oil. Two days after DMABP treatment, the rats were killed and DMABP-derived adducts were analyzed in colon and liver DNA by butanol extraction-mediated 32 P-postlabeling. Two major DNA adducts, identified as dG-C8-DMABP and dG-N 2 -DMABP, were detected in liver and colon of rats treated with DMABP. These DNA adducts were diminished approximately 35-40% with 500 ppm and 65-70% with 1,000 ppm celecoxib. In the colon, no further decline in DNA adducts was observed at 1500 ppm. The same DMABP-DNA adducts also were detected in the liver and were also diminished by celecoxib treatment. The reduction in DMABP-DNA adduct levels in celecoxib-treated animals provides further support for celecoxib as a chemopreventive agent for colorectal cancer

  10. Effects of Humidity and Surfaces on the Melt Crystallization of Ibuprofen

    Directory of Open Access Journals (Sweden)

    Il Won Kim

    2012-08-01

    Full Text Available Melt crystallization of ibuprofen was studied to understand the effects of humidity and surfaces. The molecular self-assembly during the amorphous-to-crystal transformation was examined in terms of the nucleation and growth of the crystals. The crystallization was on Al, Au, and self-assembled monolayers with –CH3, –OH, and –COOH functional groups. Effects of the humidity were studied at room temperature (18–20 °C with relative humidity 33%, 75%, and 100%. Effects of the surfaces were observed at −20 °C (relative humidity 36% to enable close monitoring with slower crystal growth. The nucleation time of ibuprofen was faster at high humidity conditions probably due to the local formation of the unfavorable ibuprofen melt/water interface. The crystal morphologies of ibuprofen were governed by the nature of the surfaces, and they could be associated with the growth kinetics by the Avrami equation. The current study demonstrated the effective control of the melt crystallization of ibuprofen through the melt/atmosphere and melt/surface interfaces.

  11. APPLICATION OF POWDERY ACTIVATED CARBONS FOR REMOVAL IBUPROFEN FROM WATER

    Directory of Open Access Journals (Sweden)

    Alicja Puszkarewicz

    2017-07-01

    Full Text Available The paper presents results of studies on the use of adsorptive properties of selected powdered activated carbons (Norit SA Super and Carbopol MB5 for removal of ibuprofen from water. The tests were performed on non-flow conditions, series depending on the type and dose of powdered adsorbents. The research was carried out on a model solution of ibuprofen at initial concentration C0 = 20 mg/dm3, at 200 C. Froundlich and Langmuir adsorption isotherms were used. Lagergrene kinetic models (PFO and Ho (PSO were used to describe adsorption kinetics. Both carbons exhibited a higher affinity for the adsorbent at a pH above 7. The better adsorbent was the Norit SA Super, for which, the highest adsorption capacity q = 0.448 g/g was achieved with dose D = 35 mg/dm3. The effectiveness of adsorption (decrease of ibuprofen in water was 78%. Total removal of ibuprofen was obtained for a dose of carbon D = 200 mg/dm3. With respect to Carbopol, the highest adsorption capacity (q = 0.353 g / g was achieved at a dose of 30 mg / dm3, resulting in a 53% efficiency. Studies have shown that both tested powdered activated carbons have contributed to effective cleaning of aqueous solutions containing ibuprofen.

  12. An integrated safety analysis of intravenous ibuprofen (Caldolor® in adults

    Directory of Open Access Journals (Sweden)

    Southworth SR

    2015-10-01

    Full Text Available Stephen R Southworth,1 Emily J Woodward,2 Alex Peng,2 Amy D Rock21North Mississippi Sports Medicine and Orthopaedic Clinic, PLLC, Tupelo, MS, 2Department of Research and Development, Cumberland Pharmaceuticals Inc., Nashville, TN, USAAbstract: Intravenous (IV nonsteroidal anti-inflammatory drugs such as IV ibuprofen are increasingly used as a component of multimodal pain management in the inpatient and outpatient settings. The safety of IV ibuprofen as assessed in ten sponsored clinical studies is presented in this analysis. Overall, 1,752 adult patients have been included in safety and efficacy trials over 11 years; 1,220 of these patients have received IV ibuprofen and 532 received either placebo or comparator medication. The incidence of adverse events (AEs, serious AEs, and changes in vital signs and clinically significant laboratory parameters have been summarized and compared to patients receiving placebo or active comparator drug. Overall, IV ibuprofen has been well tolerated by hospitalized and outpatient patients when administered both prior to surgery and postoperatively as well as for nonsurgical pain or fever. The overall incidence of AEs is lower in patients receiving IV ibuprofen as compared to those receiving placebo in this integrated analysis. Specific analysis of hematological and renal effects showed no increased risk for patients receiving IV ibuprofen. A subset analysis of elderly patients suggests that no dose adjustment is needed in this higher risk population. This integrated safety analysis demonstrates that IV ibuprofen can be safely administered prior to surgery and continued in the postoperative period as a component of multimodal pain management.Keywords: NSAID, surgical pain, fever, perioperative analgesia, critical care, multimodal pain management

  13. Comparison of Analgesic Effects of Novafen and Ibuprofen after Periodontal Surgeries

    Directory of Open Access Journals (Sweden)

    Amirreza Babaloo

    2017-01-01

    Full Text Available Introduction: Management of pain after dental procedures is one of the most important issues for dentists. Non-steroidal antiinflammatory agents, such as ibuprofen, are one of the most commonly used medications to relieve pain. Recently a new medication, Novafen, has been introduced into the Iranian pharmaceutical market, which is a combination of ibuprofen, acetaminophen and caffeine. Considering the importance of management of pain after periodontal surgeries and a paucity of studies in this respect, the present study was undertaken to compare the analgesic efficacy of Novafen and ibuprofen in alleviating pain after periodontal surgeries. Materials and methods: In the present controlled randomized clinical trial, 30 systemically healthy subjects with moderate to severe generalized chronic periodontitis, who were candidates for flap surgeries were evaluated in two groups with 30 areas in each group (two areas in each patient. After the periodontal surgical procedures, the subjects in group 1 received Novafen capsules (containing 325 mg of acetaminophen, 200 mg of ibuprofen and 40 mg of caffeine and the subjects in group 2 received ibuprofen (400 mg. The medications were selected from one pharmaceutical company and the patients only used the medications they received. The severity of pain was determined and compared at 3-minute, 1-hour and 3-hour intervals using VAS and 1, 2 and 3 days postoperatively using VRS. Results: Severity of pain at 30-minute interval in the Novafen group was significantly less than that in the ibuprofen group, with no significant differences at 1- and 3-hour intervals. However, VRS revealed significantly less pain 1, 2 and 3 days postoperatively in the Novafen group compared to the ibuprofen group. Conclusion: Based on the results of the present study, it can be concluded than Novafen can be more effective after periodontal surgeries in alleviating pain. However, its pain control capacity was similar to that of

  14. GC-MS and GC-MS/MS measurement of ibuprofen in 10-μL aliquots of human plasma and mice serum using [α-methylo-2H3]ibuprofen after ethyl acetate extraction and pentafluorobenzyl bromide derivatization: Discovery of a collision energy-dependent H/D isotope effect and pharmacokinetic application to inhaled ibuprofen-arginine in mice.

    Science.gov (United States)

    Tsikas, Dimitrios; Kayacelebi, Arslan Arinc; Hanff, Erik; Mitschke, Anja; Beckmann, Bibiana; Tillmann, Hanns-Christian; Gutzki, Frank-Mathias; Müller, Meike; Bernasconi, Corrado

    2017-02-01

    GC-MS and GC-MS/MS methods were developed and validated for the quantitative determination of ibuprofen (d 0 -ibuprofen), a non-steroidal anti-inflammatory drug (NSAID), in human plasma using α-methyl- 2 H 3 -4-(isobutyl)phenylacetic acid (d 3 -ibuprofen) as internal standard. Plasma (10μL) was diluted with acetate buffer (80μL, 1M, pH 4.9) and d 0 - and d 3 -ibuprofen were extracted with ethyl acetate (2×500μL). After solvent evaporation d 0 - and d 3 -ibuprofen were derivatized in anhydrous acetonitrile by using pentafluorobenzyl (PFB) bromide and N,N-diisopropylethylamine as the base catalyst. Under electron-capture negative-ion chemical ionization (ECNICI), the PFB esters of d 0 - and d 3 -ibuprofen readily ionize to form their carboxylate anions [M-PFB] - at m/z 205 and m/z 208, respectively. Collision-induced dissociation (CID) of m/z 205 and m/z 208 resulted in the formation of the anions at m/z 161 and m/z 164, respectively, due to neutral loss of CO 2 (44 Da). A collision energy-dependent H/D isotope effect was observed, which involves abstraction/elimination of H - from d 0 -ibuprofen and D - from d 3 -ibuprofen and is minimum at a CE value of 5eV. Quantitative GC-MS determination was performed by selected-ion monitoring of m/z 205 and m/z 208. Quantitative GC-MS/MS determination was performed by selected-reaction monitoring of the mass transitions m/z 205 to m/z 161 for d 0 -ibuprofen and m/z 208 to m/z 164 for d 3 -ibuprofen. In a therapeutically relevant concentration range (0-1000μM) d 0 -ibuprofen added to human plasma was determined with accuracy (recovery, %) and imprecision (relative standard deviation, %) ranging between 93.7 and 110%, and between 0.8 and 4.9%, respectively. GC-MS (y) and GC-MS/MS (x) yielded almost identical results (y=4.00+0.988x, r 2 =0.9991). In incubation mixtures of arachidonic acid (10μM), d 3 -ibuprofen (10μM) or d 0 -ibuprofen (10μM) with ovine cyclooxygenase (COX) isoforms 1 and 2, the concentration of d 3

  15. Effect Of Formulating Additives On The Properties Of Ibuprofen Tablets

    African Journals Online (AJOL)

    A study of the comparative effects of different formulating additives and film coating on the properties of ibuprofen tablets was made. The tested properties were hardeness (H), friability (F), the disintegration time (D) and dissolution characteristics of ibuprofen tablets. The hardeness, friability, the hardeness friability ratio ...

  16. The potential role of cyclooxygenase-2 inhibitors in the treatment of experimentally-induced mammary tumour: does celecoxib enhance the anti-tumour activity of doxorubicin?

    Science.gov (United States)

    Awara, Wageh M; El-Sisi, Alaa E; El-Sayad, Magda E; Goda, Ahmed E

    2004-11-01

    The potential anti-tumour activity of non-steroidal anti-inflammatory drugs (NSAIDS) has been previously discussed. This study was undertaken to assess the possible anti-tumour activity of the cyclooxygenase-2 (COX-2) inhibitor; celecoxib in an animal model of mammary carcinoma; the solid Ehrlich carcinoma (SEC). The possibility that celecoxib may modulate the anti-tumour activity of doxorubicin on the SEC was also studied. Some of the possible mechanisms underlying such modulation were investigated. The anti-tumour activity of celecoxib (25 mg kg(-1)), diclofenac (12.5 mg kg(-1)) and doxorubicin (2 mg kg(-1)) either alone or in combination were investigated on SEC in vivo through the assessment of tumour growth delay (TGD) and tumour volume (TV), changes in tumour DNA content and nitric oxide (NO) levels, immunohistochemical staining of the tumour suppressor gene product; p53 histopathological examination and determination of apoptotic index of SEC. In addition, the influence of these drugs on the DNA fragmentation pattern of Ehrlich carcinoma cells (ECC) was studied. It was found that both celecoxib and diclofenac lack the anti-tumour activity on SEC. In addition there was a significant increase in doxorubicin anti-tumour activity when administered in combination with celecoxib. Moreover, it was found that both celecoxib and diclofenac have the potential to inhibit the function of P-glycoprotein (P-gp) in ECC using rhodamine uptake and efflux assays. Therefore, the current study suggested the chemosensitizing potential of celecoxib in the SEC animal model of mammary tumour, which could be explained in part on the basis of inhibition of P-gp function, with possible enhancement of doxorubicin anti-tumour activity.

  17. Celecoxib offsets the negative renal influences of cyclosporine via modulation of the TGF-β1/IL-2/COX-2/endothelin ET(B) receptor cascade.

    Science.gov (United States)

    El-Gowelli, Hanan M; Helmy, Maged W; Ali, Rabab M; El-Mas, Mahmoud M

    2014-03-01

    Endothelin (ET) signaling provokes nephrotoxicity induced by the immunosuppressant drug cyclosporine A (CSA). We tested the hypotheses that (i): celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, counterbalances renal derangements caused by CSA in rats and (ii) the COX-2/endothelin ET(B) receptor signaling mediates the CSA-celecoxib interaction. Ten-day treatment with CSA (20 mg/kg/day) significantly increased biochemical indices of renal function (serum urea, creatinine), inflammation (interleukin-2, IL-2) and fibrosis (transforming growth factor-β₁, TGF-β₁). Histologically, CSA caused renal tubular atrophy along with interstitial fibrosis. These detrimental renal effects of CSA were largely reduced in rats treated concurrently with celecoxib (10 mg/kg/day). We also report that cortical glomerular and medullary tubular protein expressions of COX-2 and ET(B) receptors were reduced by CSA and restored to near-control values in rats treated simultaneously with celecoxib. The importance of ET(B) receptors in renal control and in the CSA-celecoxib interaction was further verified by the findings (i) most of the adverse biochemical, inflammatory, and histopathological profiles of CSA were replicated in rats treated with the endothelin ETB receptor antagonist BQ788 (0.1 mg/kg/day, 10 days), and (ii) the BQ788 effects, like those of CSA, were alleviated in rats treated concurrently with celecoxib. Together, the data suggest that the facilitation of the interplay between the TGF-β1/IL-2/COX-2 pathway and the endothelin ET(B) receptors constitutes the cellular mechanism by which celecoxib ameliorates the nephrotoxic manifestations of CSA in rats. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Análisis coste-efectividad del empleo de celecoxib en el tratamiento de la artrosis

    Directory of Open Access Journals (Sweden)

    Moreno A.

    2003-01-01

    Full Text Available Antecedentes: Los antiinflamatorios no esteroideos (AINE, utilizados en el tratamiento de la artrosis, pueden producir reacciones adversas gastrointestinales (GI graves. Celecoxib, un inhibidor específico de la ciclooxigenasa 2 (COX-2, ha demostrado una eficacia equivalente a los AINE convencionales con un mejor perfil de tolerabilidad y seguridad. Objetivo: La finalidad de este estudio ha sido realizar un análisis coste-efectividad sobre el uso de celecoxib frente a los AINE clásicos en el tratamiento de la artrosis. Material y métodos: El análisis coste-efectividad se ha diseñado mediante un modelo farmacoeconómico, definiéndose como unidad de efectividad a cada año de vida ganado tras la toma de celecoxib o AINE. La probabilidad de que aparezcan los diferentes resultados clínicos se ha obtenido de artículos publicados y de asunciones incorporadas. Sólo se han valorado los costes directos médicos (medicación, hospitalización, pruebas complementarias, analíticas, visitas extras, etc., sin haberse incluido otros costes. La perspectiva del estudio ha sido la del Sistema Nacional de Salud y el horizonte temporal elegido ha sido de 6 meses. Resultados: El coste adicional por cada año de vida ganado secundario al uso de celecoxib frente a los AINE clásicos asciende a 8.017 ? (1.333.834 ptas.. El análisis de sensibilidad muestra cómo estos valores son sensibles a la modificación del coste de AINE y gastroprotector, así como a la inclusión de grupos poblacionales con edades más bajas. Conclusiones: Celecoxib puede ser considerado como una opción coste-efectiva en el tratamiento de la artrosis, ya que va a evitar muertes y a ganar años de vida para los pacientes con un coste adicional razonable y moderado, cuando se compara con los AINE. Su eficiencia aumenta a medida que se utiliza en poblaciones con menor edad media y, probablemente, en aquellas con mayor riesgo de desarrollar complicaciones GI.

  19. Synthesis, Characterization, and Biodistribution of Quantum Dot-Celecoxib Conjugate in Mouse Paw Edema Model

    Directory of Open Access Journals (Sweden)

    Suresh K. Kalangi

    2018-01-01

    Full Text Available Increased risk of cardiovascular side effects has been reported with many of the drugs in the market, including nonsteroidal anti-inflammatory drugs (NSAIDs. Hence, it is critical to thoroughly evaluate the biodistribution and pharmacokinetic properties of the drugs. Presently nanotechnology in combination with noninvasive imaging techniques such as magnetic resonance imaging (MRI, computed axial tomography (CAT, and positron emission tomography (PET provides a better estimate of the spatio-temporal distribution of therapeutic molecules. Optical imaging using quantum dot- (QD- tagged biological macromolecules is emerging as a fast, economical, sensitive, and safer alternative for theranostic purposes. In the present study, we report the nanoconjugates of mercaptopropionic acid- (MPA- capped CdTe quantum dots (QDs and Celecoxib for bio-imaging in carrageenan-induced mouse paw edema model of inflammation. QD-Celecoxib conjugates were characterized by fluorescence, FT-IR, NMR, and zeta-potential studies. In vivo imaging of QD-Celecoxib conjugates showed clear localization in the inflamed tissue of mouse paw within 3 h, with a gradual increase reaching a maximum and a later decline. This decrease of fluorescence in the paw region is followed by an increase in urinary bladder region, suggesting the possible excretion of QD-drug conjugates from mice within 24 h.

  20. Ibuprofen Differentially Affects Supraspinatus Muscle and Tendon Adaptations to Exercise in a Rat Model.

    Science.gov (United States)

    Rooney, Sarah Ilkhanipour; Baskin, Rachel; Torino, Daniel J; Vafa, Rameen P; Khandekar, Pooja S; Kuntz, Andrew F; Soslowsky, Louis J

    2016-09-01

    Previous studies have shown that ibuprofen is detrimental to tissue healing after acute injury; however, the effects of ibuprofen when combined with noninjurious exercise are debated. Administration of ibuprofen to rats undergoing a noninjurious treadmill exercise protocol will abolish the beneficial adaptations found with exercise but will have no effect on sedentary muscle and tendon properties. Controlled laboratory study. A total of 167 male Sprague-Dawley rats were divided into exercise or cage activity (sedentary) groups and acute (a single bout of exercise followed by 24 hours of rest) and chronic (2 or 8 weeks of repeated exercise) response times. Half of the rats were administered ibuprofen to investigate the effects of this drug over time when combined with different activity levels (exercise and sedentary). Supraspinatus tendons were used for mechanical testing and histologic assessment (organization, cell shape, cellularity), and supraspinatus muscles were used for morphologic (fiber cross-sectional area, centrally nucleated fibers) and fiber type analysis. Chronic intake of ibuprofen did not impair supraspinatus tendon organization or mechanical adaptations (stiffness, modulus, maximum load, maximum stress, dynamic modulus, or viscoelastic properties) to exercise. Tendon mechanical properties were not diminished and in some instances increased with ibuprofen. In contrast, total supraspinatus muscle fiber cross-sectional area decreased with ibuprofen at chronic response times, and some fiber type-specific changes were detected. Chronic administration of ibuprofen does not impair supraspinatus tendon mechanical properties in a rat model of exercise but does decrease supraspinatus muscle fiber cross-sectional area. This fundamental study adds to the growing literature on the effects of ibuprofen on musculoskeletal tissues and provides a solid foundation on which future work can build. The study findings suggest that ibuprofen does not detrimentally affect

  1. Preemptive Analgesia with Ibuprofen and Acetaminophen in Pediatric Lower Abdominal Surgery

    Directory of Open Access Journals (Sweden)

    P Kashefi

    2005-07-01

    Full Text Available Background: Postoperative pain is a significant problem in pediatrics. Preemptive administration of analgesics has recently emerged as a method to enhance pain management associated with surgery. The objective of this study was to compare the analgesic efficacy of a single-dose of preoperative oral ibuprofen versus acetaminophen in preventing pain after lower abdominal surgery in pediatrics. Methods: In this randomized, double-blind study, following lower abdominal surgery, 75 children, aging 3 to 12 years, were assigned to receive either ibuprofen 20 mg /kg (n=25 or acetaminophen 35 mg/kg (n=25 or placebo (n=25 2 hours before surgery. Agitation in recovery was measured and postoperative pain was quantified 3 and 24 hours after surgery by Oucher’s scale. The amount of postoperative analgesic needed in the ward was also assessed. Results: It was found that preoperative administration of ibuprofen and acetaminophen can reduce agitation in recovery but there was no difference in the agitation score between ibuprofen and acetaminophen groups (P=0.145. Agitation score was significantly lower in ibuprofen group compared to placebo (P>0.005. Similarly, patients in the acetaminophen group were considerably less agitated than those in the placebo group (P=0.002. No significant difference was observed in pain intensity 3 and 24 hours after operation between the three groups [(P=0.495 and (P=0.582 respectively]. The amount of postoperative analgesic needed during ward hospitalization was not significantly different among the three groups (P>0.005. Conclusion: These results provide evidence that preemptive acetaminophen and ibuprofen may reduce agitation during recovery but they neither improve the postoperative pain nor reduce analgesics consumption in ward Key words: Postoperative analgesia, Acetaminophen, Ibuprofen, Preemptive analgesia

  2. Dose-dependent reduction of 3,2'-dimethyl-4-aminobiphenyl-derived DNA adducts in colon and liver of rats administered celecoxib

    Energy Technology Data Exchange (ETDEWEB)

    Ravoori, Srivani [James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Feng Yi; Neale, Jason R. [James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Jeyabalan, Jeyaprakash [James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Srinivasan, Cidambi [Department of Statistics, University of Kentucky, Lexington, KY 40502 (United States); Hein, David W. [James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Gupta, Ramesh C. [James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202 (United States)], E-mail: rcgupta@louisville.edu

    2008-02-01

    Colon cancer is second leading cause of cancer-related deaths in Western countries. Diet and smoking, which contain aromatic and heterocyclic amines, are major risk factors for colon cancer. Colorectal cancers have a natural history of long latency and therefore provide ample opportunities for effective chemoprevention. 3,2'-Dimethyl-4-aminobiphenyl (DMABP) is an experimental aromatic amine that causes cancer in rat colon and serves as an experimental model for arylamine and heterocyclic amine mutagens derived from diet and smoking. In this study, we investigated the effects of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor on DMABP-induced DNA adduct formation in rat liver and colon. Male F-344 rats (5-week old) were provided free access to modified AIN-76A rat chow containing 0 (control), 500, 1000, or 1500 ppm celecoxib. Two weeks later, the rats received a subcutaneous injection of 100 mg/kg DMABP in peanut oil. Two days after DMABP treatment, the rats were killed and DMABP-derived adducts were analyzed in colon and liver DNA by butanol extraction-mediated {sup 32}P-postlabeling. Two major DNA adducts, identified as dG-C8-DMABP and dG-N{sup 2}-DMABP, were detected in liver and colon of rats treated with DMABP. These DNA adducts were diminished approximately 35-40% with 500 ppm and 65-70% with 1,000 ppm celecoxib. In the colon, no further decline in DNA adducts was observed at 1500 ppm. The same DMABP-DNA adducts also were detected in the liver and were also diminished by celecoxib treatment. The reduction in DMABP-DNA adduct levels in celecoxib-treated animals provides further support for celecoxib as a chemopreventive agent for colorectal cancer.

  3. Molecular Basis for Allosteric Inhibition of Acid-Sensing Ion Channel 1a by Ibuprofen

    DEFF Research Database (Denmark)

    Lynagh, Timothy; Romero-Rojo, José Luis; Lund, Camilla

    2017-01-01

    -clamp fluorometry. Our results show that ibuprofen is an allosteric inhibitor of ASIC1a, which binds to a crucial site in the agonist transduction pathway and causes conformational changes that oppose channel activation. Ibuprofen inhibits several ASIC subtypes, but certain ibuprofen derivatives show some...

  4. Celecoxib restores angiogenic factor expression at the maternal-fetal interface in the BPH/5 mouse model of preeclampsia.

    Science.gov (United States)

    Reijnders, Dorien; Liu, Chin-Chi; Xu, Xinjing; Zhao, Anna M; Olson, Kelsey N; Butler, Scott D; Douglas, Nataki C; Sones, Jenny L

    2018-05-01

    Preeclampsia (PE), a hypertensive disease of pregnancy, is a leading cause of fetal and maternal morbidity/mortality. Early angiogenic and inflammatory disturbances within the placenta are thought to underlie the development of the maternal PE syndrome and poor pregnancy outcomes. However, the exact etiology remains largely unknown. Here, we use the BPH/5 mouse model of PE to elucidate the way in which inflammation early in pregnancy contributes to abnormal expression of angiogenic factors at the maternal-fetal interface. We have previously described improvement in maternal hypertension and fetal growth restriction in this model after treatment with the anti-inflammatory cyclooxygenase-2 (Cox2) specific inhibitor celecoxib. To further characterize the mechanisms by which celecoxib improves poor pregnancy outcomes in BPH/5 mice, we determined expression of angiogenic factors and complement pathway components after celecoxib. In BPH/5 implantation sites there was increased hypoxia inducible factor-1α ( Hif1α), heme oxygenase-1 ( Ho-1), and stem cell factor ( Scf) mRNA concomitant with elevated prostaglandin synthase 2 ( Ptgs2), encoding Cox2, and elevated VEGF protein. Angiopoietin 1 ( Ang1), tunica interna endothelial cell kinase-2 receptor ( Tie2), complement factor 3 ( C3), and complement factor B ( CfB) were increased in midgestation BPH/5 placentae. Whereas BPH/5 expression levels of VEGF, Ang1, and Tie2 normalized after celecoxib, placental C3 and CfB mRNA remained unchanged. However, celecoxib did reduce the pregnancy-specific circulating soluble fms-like tyrosine kinase-1 (sFlt-1) rise in BPH/5 mice at midgestation. These data show that elevated Cox2 during implantation contributes to placental angiogenic factor imbalances in the BPH/5 mouse model of PE.

  5. The Evidence Base on the Efficacy and Safety of Ibuprofen in Pediatrics

    Directory of Open Access Journals (Sweden)

    Yu.V. Marushko

    2013-10-01

    Full Text Available The article deals with an analysis of the world literature of recent years, the aim of which was to study the efficacy and safety of ibuprofen use as first-line antipyretic in pediatric practice. Special attention was paid to researches on the study the pharmacokinetics, efficacy and safety of ibuprofen in fever in children of all ages, as well as the use of different forms of ibuprofen (suspension, suppositories.

  6. Pilot monitoring study of ibuprofen in surface waters of north of Portugal

    OpenAIRE

    Paíga, Paula; Santos, Lúcia; Amorim, Célia G.; Araújo, Alberto N.; Montenegro, M. Conceição B. S. M.; Pena, Angelina; Delerue-Matos, Cristina

    2013-01-01

    Ibuprofen is amongst the most worldwide consumed pharmaceuticals. The present work presents the first data in the occurrence of ibuprofen in Portuguese surface waters, focusing in the north area of the country, which is one of the most densely populated areas of Portugal. Analysis of ibuprofen is based on pre-concentration of the analyte with solid phase extraction and subsequent determination with liquid chromatography coupled to fluorescence detection. A total of 42 ...

  7. Resolution of ibuprofen: a project for an experimental organic chemistry course

    International Nuclear Information System (INIS)

    Romero, Adriano L.; Baptistella, Lucia H.B.; Coelho, Fernando; Imamura, Paulo M.

    2012-01-01

    A practical and didactic sequence of experiments was proposed to illustrate the stereochemistry concept, optically active compounds, resolution of racemates, and use of the NMR technique, including 2D-COSY for identification of organic compounds, on a laboratory course for undergraduate students. The sequence was: extractions of racemic ibuprofen and chiral naproxen from commercial tablets; syntheses of diastereoisomeric amides reacting chiral (S)-(-)-α-methylbenzylamine with (+-)-ibuprofen; separation and determination of absolute configuration of amides by 1 H NMR spectroscopy and GC analysis, and hydrolysis of amides to obtain (+)- and (-)-ibuprofen. (author)

  8. IBUPROFEN IN COMPLEX TREATMENT OF FEVER IN CHILDREN

    Directory of Open Access Journals (Sweden)

    А.А. Alexeeva

    2011-01-01

    Full Text Available Pain and fever are one of the most frequent conditions in pediatric practice. Frequent occurrence of fever accompanied by a pain syndrome stipulates combined antipyretic and analgesic medications. This article contains information upon ibuprofen use («Nurofen for children» in pediatric patients as an antipyretic and analgesic medication to be used as part of complex treatment of acute respiratory infections.Key words: fewer, children, ibuprofen. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (6: 137–140

  9. A Transporter of Ibuprofen is Upregulated in MDCK I Cells under Hyperosmotic Culture Conditions

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Rasmussen, Rune N; Mo, Junying

    2016-01-01

    Ibuprofen is a widely used drug. It has been identified as an inhibitor of several transporters, but it is not clear if ibuprofen is a substrate of any transporter itself. In the present work, we have characterized a transporter of ibuprofen, which is upregulated by hyperosmotic culture conditions...... in Madin-Darby canine kidney I (MDCK I) renal cells. [(3)H]-Ibuprofen uptake rate was measured in MDCK I cell cultured under normal (300 mOsm) and hyperosmotic (500 mOsm) conditions. Hyperosmotic conditions were obtained by supplementing urea, NaCl, mannitol, or raffinose to culture medium. The effect...... of increased osmolarity was investigated for different incubation times. [(3)H]-Ibuprofen uptake in MDCK I cells was upregulated by hyperosmotic culture condition, and was saturable with a Km value of 0.37 ± 0.08 μM and a Vmax of 233.1 ± 17.2 pmol· cm(-2)· min(-1). Racemic [(3)H]-ibuprofen uptake could...

  10. Pharmacokinetics of Cromolyn and Ibuprofen in Healthy Elderly Volunteers.

    Science.gov (United States)

    Brazier, David; Perry, Robert; Keane, Jim; Barrett, Katie; Elmaleh, David R

    2017-11-01

    BACKGROUND AND OBJECTIVES: The combination of cromolyn and ibuprofen is being investigated as a treatment for early Alzheimer's disease (AD). This study investigated the pharmacokinetics, safety, and tolerability of cromolyn and ibuprofen co-administration in healthy elderly adult volunteers. In this open-labeled study, 26 subjects, aged 55-75 years, received co-administration of inhaled cromolyn (single dose 17.1 mg; double dose 34.2 mg total) and oral ibuprofen (single dose 10 mg; double dose 20 mg total). Blood sampling was performed for 6 h after co-administration in all subjects; cerebrospinal fluid (CSF) was collected in three to four subjects per cohort for 4 h following co-administration. Safety parameters, including adverse events (AEs), were monitored throughout the study. For cromolyn, the mean (±SD) maximum observed concentration (C max ) in plasma was 46.69 ± 32.97 and 96.75 ± 46.22 ng/ml after single- and double-dose inhalation, respectively [time to C max (t max ) ~22 min for each; terminal elimination half-life (t ½ ) ~1.8 h for each]. For ibuprofen, the plasma C max was 1090.98 ± 474.64 ng/ml and 2062.96 ± 655.13 ng/ml after single- and double-dose oral administration, respectively (t max ~1.6-1.8 h; t ½ ~1.9 h for each). For cromolyn, the CSF C max was 0.24 ± 0.08 ng/ml at 3.72 ± 0.70 h after single-dose administration and 0.34 ± 0.17 ng/ml at 3.45 ± 0.95 h after double-dose administration, and for ibuprofen, the CSF C max was 3.94 ± 1.29 ng/ml at 2.55 ± 0.96 h after single-dose administration and 8.93 ± 3.29 ng/ml at 3.15 ± 1.05 h after double-dose administration. Three (12%) subjects reported mild or moderate AEs which were unlikely to be related to study drug. The combination of cromolyn and ibuprofen was safe and well tolerated. The concentrations of cromolyn and ibuprofen observed in the CSF are considered sufficient to titrate the estimated daily amyloid production and the associated inflammatory response

  11. Celecoxib Alleviates Memory Deficits by Downregulation of COX-2 Expression and Upregulation of the BDNF-TrkB Signaling Pathway in a Diabetic Rat Model.

    Science.gov (United States)

    Yang, Ying; Gao, Ling

    2017-06-01

    Previous studies conveyed that diabetes causes learning and memory deficits. Data also suggest that celecoxib exerts an anti-hyperalgesic, anti-allodynic, and a plethora of other beneficial effects in diabetic rats. However, whether celecoxib could alleviate memory deficit in diabetic rat is unknown. In the present study, we aimed to examine the potential of celecoxib to counter memory deficits in diabetes. Experimental diabetes was induced by streptozotocin (STZ, 60 mg/kg) in male SD rats. Rats were divided into three groups (n = 16/group): normal control group injected with normal saline, diabetes group injected with STZ, and diabetes + celecoxib group in which diabetic rats were administered with celecoxib by gavage in drinking water (10 mg/kg) for 10 days in terms of which memory performance in animals was measured, hippocampal tissue harvested, and long-term potentiation assessed. Western blotting and immunohistochemical staining were performed to determine cyclooxygenase 2 (COX-2) expression in hippocampus. The results showed that a rat model of STZ-induced diabetes was successfully established and that celecoxib treatment significantly improved the associated nephropathy and inflammation. Moreover, spatial memory and hippocampal long-term potentiation (LTP) were impaired in diabetic model (P memory deficit and hippocampal LTP in the diabetic rats. To understand the underlying mechanisms, the expression of some important pathways involved in memory impairment was determined. We found that brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin-related kinase (p-TrkB) were decreased in diabetic rats but were effectively reversed by celecoxib treatment. As evidenced by western blotting and immunohistochemical staining, the expression of COX-2 in hippocampus was significantly upregulated in diabetic rat (P memory deficits via probable downregulation of hippocampal COX-2 expression and upregulation of the BDNF-TrkB signaling pathway in a

  12. The use of etoricoxib to treat an idiopathic stabbing headache: a case report

    Directory of Open Access Journals (Sweden)

    O'Connor Mortimer B

    2007-09-01

    Full Text Available Abstract According to the International Headache Society, idiopathic stabbing headache (ISH, an indomethacin-responsive headache syndrome, is a paroxysmal disorder of short duration manifested as head pain occurring as a single stab or a series of stabs involving the area supplied in the distribution of the first division of the trigeminal nerve. Stabs last for approximately a few seconds, occurring and recurring from once to multiple times per day in an irregular frequency, with no underlying attributable disorder. Previously indomethacin was the principle treatment option for ISH, despite therapeutic failure in up to 35% of cases, until reports showed gabapentin, melatonin and selective cyclo-oxygenase-2 (COX-2 inhibitors were also possibly effective. In this report we present the full case report of an 88 year old lady with a history of untreated ISH where etoricoxib, a selective COX-2 inhibitor, was used to effectively treat her ISH.

  13. Celecoxib enhances radiation response of secondary bone tumors of a human non-small cell lung cancer via antiangiogenesis in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Klenke, Frank Michael [Bern Univ. (Switzerland). Dept. of Orthopedic Surgery; Abdollahi, Amir [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Tufts Univ. School of Medicine, Boston, MA (United States). Center of Cancer Systems Biology; Bischof, Marc; Huber, Peter E. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Gebhard, Martha-Maria [Heidelberg Univ. (Germany). Dept. of Experimental Surgery; Ewerbeck, Volker [Heidelberg Univ. (Germany). Dept. of Orthopedic Surgery; Sckell, Axel [Charite Univ. Medical Center, Berlin (Germany). Dept. of Orthopedic, Trauma and Reconstructive Surgery

    2011-01-15

    Purpose: Cyclooxygenase-2 (COX-2) inhibitors mediate a systemic antitumor activity via antiangiogenesis and seem to enhance the response of primary tumors to radiation. Radiosensitizing effects of COX-2 inhibition have not been reported for bone metastases. Therefore, the aim of this study was the investigation of the radiosensitizing effects of the selective COX-2 inhibitor celecoxib in secondary bone tumors of a non-small cell lung carcinoma in vivo. Materials and Methods: Human A549 lung carcinomas were implanted into a cranial window preparation in male SCID mice (n = 24). Animals were treated with either celecoxib or radiation (7 Gy single photon dose) alone or a combination of celecoxib and radiation, respectively. Untreated animals served as controls. The impact of radiation and COX-2 inhibition on angiogenesis, microcirculation, and tumor growth was analyzed over 28 days by means of intravital microscopy and histological methods. Results: Monotherapies with radiation as well as celecoxib had significant antitumor effects compared to untreated controls. Both therapies reduced tumor growth and vascularization to a similar extent. The simultaneous administration of celecoxib and radiation further enhanced the antitumor and antiangiogenic effects of single-beam radiation. With the combined treatment approach, tumor vascularization and tumor size were decreased by 57% and 51%, respectively, as compared to monotherapy with radiation. Conclusion: The combined application of radiation therapy and COX-2 inhibition showed synergistic effects concerning the inhibition of tumor growth and tumor angiogenesis. Therefore, the combination of radiation with COX-2 inhibitor therapy represents a promising approach to improve the therapeutic efficacy of radiotherapy of bone metastases. (orig.)

  14. Design of Agglomerated Crystals of Ibuprofen During Crystallization: Influence of Surfactant

    Directory of Open Access Journals (Sweden)

    Maryam Maghsoodi

    2011-01-01

    Full Text Available Objective(sIbuprofen is a problematic drug in tableting, and dissolution due to its poor solubility, hydrophobicity, and tendency to stick to surface. Because of the bad compaction behavior ibuprofen has to be granulated usually before tableting. However, it would be more satisfactory to obtain directly during the crystallization step crystalline particles that can be directly compressed and quickly dissolved. Materials and Methods Crystallization of ibuprofen was carried out using the quasi emulsion solvent diffusion method in presence of surfactant (sodium lauryl sulfate (SLS, Tween 80. The particles were characterized by differential scanning calorimetry (DSC, powder X-ray diffraction (XRPD and were evaluated for particle size, flowability, drug release and tableting behavior. ResultsIbuprofen particles obtained in the presence of surfactants consisted of numerous plate- shaped crystals which had agglomerated together as near spherical shape. The obtained agglomerates exhibited significantly improved micromeritic properties as well as tableting behavior than untreated drug crystals. The agglomerates size and size distribution was largely controlled by surfactant concentration, but there was no significant influence found on the tableting properties. The dissolution tests showed that the agglomerates obtained in presence of SLS exhibited enhanced dissolution rate while the agglomerates made in the presence of Tween 80 had no significant impact on dissolution rate of ibuprofen in comparison to untreated sample. The XRPD and DSC results showed that during the agglomeration process, ibuprofen did not undergo any polymorphic changes.Conclusion The study highlights the influence of surfactants on crystallization process leading to modified performance.

  15. Modification of the crystal habit of celecoxib for improved processability.

    Science.gov (United States)

    Banga, Sheere; Chawla, Garima; Varandani, Deepak; Mehta, B R; Bansal, Arvind K

    2007-01-01

    Crystallization is often used in the pharmaceutical industry for purification and isolation of drugs, and also as a means of generating polymorphs or isomorphs. The aim of this study was to investigate the role of extrinsic crystallization parameters on the crystallized product, with special emphasis on improving the mechanical properties of acicular celecoxib. Celecoxib isomorphs were prepared using different techniques (solvent crystallization and vapour diffusion) and crystallization conditions (solvents, stirring, degree of supersaturation, crystallization temperature and seeding). Powder X-ray diffractometry, spectroscopic and thermal methods were used to investigate physical characteristics of crystals. Growth kinetics and aggregation dynamics of crystallization in polar and non-polar solvents were simulated using a dynamic light scattering method. The quick appearance of broad peaks over the range of 10-8000 nm in chloroform during crystallization simulation studies indicated faster aggregation in non-polar solvents. Aspect ratio, flow, compressibility and surface area of recrystallized products were also determined. Surface topography was determined by atomic force microscopy and the lath-shaped crystals (aspect ratio of 2-4) exhibited a roughness index of 1.79 in comparison with 2.92 for needles. Overall, the lath-shaped isomorphs exhibited improved flow and better compressibility.

  16. Celecoxib as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial.

    Science.gov (United States)

    Asadabadi, Mahtab; Mohammadi, Mohammad-Reza; Ghanizadeh, Ahmad; Modabbernia, Amirhossein; Ashrafi, Mandana; Hassanzadeh, Elmira; Forghani, Saeedeh; Akhondzadeh, Shahin

    2013-01-01

    Autism is associated with activation of the inflammatory response system. This study aims to assess the efficacy of a cyclooxygenase-2 inhibitor, celecoxib, as adjunctive therapy in the treatment of autism In a 10-week randomized double-blind placebo-controlled study, 40 outpatient children with a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision clinical diagnosis of autism were randomly allocated to celecoxib plus risperidone or placebo plus risperidone. The dose of risperidone and celecoxib were titrated up to 3 and 300 mg/day, respectively. Patients were assessed at baseline and after 2, 4, 6, and 10 weeks of starting medication using the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale. Primary outcome measure was the change in irritability subscale of ABC-C. Significant time × treatment interaction was observed for Irritability (F (1.658, 63.021) = 13.580, P autism. (Registration, www.irct.ir ; IRCT138711091556N2).

  17. Enhancement of transdermal delivery of ibuprofen using microemulsion vehicle.

    Science.gov (United States)

    Hu, Liandong; Hu, Qiaofeng; Yang, Jianxue

    2014-10-01

    The objective of this study was to find a stable microemulsion vehicle for transdermal delivery of ibuprofen to improve the skin permeability. Microemulsion was prepared using different sorts of oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were used to evaluate the microemulsion domain. The effects of oleic acid and surfactant mixture on skin permeation of ibuprofen were evaluated with excised skins. The optimum formulation F3 consisting of 6% oleic acid, 30% Cremophor RH40/Transcutol P (2:1, w/w) and 59% water phase, showed a high permeation rate of 42.98 µg/cm(2)/hr. The mean droplet size of microemulsion was about 43 nm and no skin irritation signs were observed on the skin of rabbits. These results indicated that this novel microemulsion is a useful formulation for the transdermal delivery of ibuprofen.

  18. Antiproliferative effect of a novel nitro-oxy derivative of celecoxib in human colon cancer cells: role of COX-2 and nitric oxide.

    Science.gov (United States)

    Bocca, Claudia; Bozzo, Francesca; Bassignana, Andrea; Miglietta, Antonella

    2010-07-01

    It has been shown previously that a novel nitrooxy derivative of celecoxib exerts antiproliferative and pro-apoptotic effects in human colon cancer cells. The aim of this study was to elucidate whether these biological properties depend on COX-2 inhibition and/or NO release. Therefore, the derivative was decomposed into the parent compound celecoxib and the NO donor benzyl nitrate and the biological role of each was tested in COX-2-positive (HT-29) and -negative (SW-480) colon cancer cells. The main findings were that the nitro-oxy derivative behaved like celecoxib in HT-29 cells in terms of COX-2 and ERK/MAPK inhibition, as well as induction of apoptosis, while the benzyl nitrate had no such effects. Interestingly, the beta-catenin system was activated by the nitro-oxy derivative as well as by benzyl nitrate alone more potently than by the parent compound celecoxib, suggesting a possible regulatory role for NO. In SW480 cells, these activities were substantially less pronounced, suggesting the presence of COX-2-dependent mechanisms in the modulation of these parameters.

  19. Phase III study of ibuprofen versus placebo for radiation-induced genitourinary side effects

    International Nuclear Information System (INIS)

    Coleman, C. Norman; Kelly, Laura; Riese Daly, Nancy; Beard, Clair; Kaplan, Irving; Lamb, Carolyn; Propert, Kathleen; Manola, Judith

    2002-01-01

    Purpose: On the basis of our anecdotal clinical observations that nonsteroidal anti-inflammatory agents relieved dysuria during radiotherapy for patients with prostate cancer, we conducted a Phase III randomized trial of ibuprofen vs. placebo for patients who had an increase in acute urinary symptoms. Our in vitro and in vivo laboratory data with a higher concentration of ibuprofen than achievable in this study demonstrated radiosensitization. This study examined whether the inflammatory response within the prostate during radiotherapy would respond to the standard dose of ibuprofen as assessed by a symptom score. Methods and Materials: Patients were registered to the study and were followed weekly with a formal symptom assessment. A double-blind randomization to ibuprofen, 400 mg q.i.d., vs. placebo for 7 days was done at a time when the severity score increased. The symptom response was evaluated at the end of the week. Results: Between 1995 and 1998, 100 patients were entered, 28 did not have a sufficient change in symptom score to be randomized, and 19 were either unable to take ibuprofen or withdrew before randomization. Of the 53 patients randomized, 27 received placebo and 26 ibuprofen. No statistically significant differences were found between the placebo and ibuprofen groups between baseline and randomization or between randomization and the 1-week posttreatment assessment. Neither group had a change in symptom severity between randomization and the 1-week posttreatment evaluation. Conclusion: The standard anti-inflammatory dose of ibuprofen did not relieve the acute urinary or rectal symptoms during radiotherapy for prostate cancer. The nonsteroidal anti-inflammatory drugs are potential radiation sensitizers with the mechanism of action as yet unknown. Clinical trials of the cyclooxygenase inhibitors as radiation sensitizers should explore a range of doses and evaluate potential mechanisms of action, including cyclooxygenase inhibition and other non

  20. Phytoextraction, phytotransformation and rhizodegradation of ibuprofen associated with Typha angustifolia in a horizontal subsurface flow constructed wetland.

    Science.gov (United States)

    Li, Yifei; Zhang, Jiefeng; Zhu, Guibing; Liu, Yu; Wu, Bing; Ng, Wun Jern; Appan, Adhityan; Tan, Soon Keat

    2016-10-01

    Widespread occurrence of trace pharmaceutical residues in aquatic environments is of great concerns due to the potential chronic toxicity of certain pharmaceuticals including ibuprofen on aquatic organisms even at environmental levels. In this study, the phytoextraction, phytotransformation and rhizodegradation of ibuprofen associated with Typha angustifolia were investigated in a horizontal subsurface flow constructed wetland system. The experimental wetland system consisted of a planted bed with Typha angustifolia and an unplanted bed (control) to treat ibuprofen-loaded wastewater (∼107.2 μg L(-1)). Over a period of 342 days, ibuprofen was accumulated in leaf sheath and lamina tissues at a mean concentration of 160.7 ng g(-1), indicating the occurrence of the phytoextraction of ibuprofen. Root-uptake ibuprofen was partially transformed to ibuprofen carboxylic acid, 2-hydroxy ibuprofen and 1-hydroxy ibuprofen which were found to be 1374.9, 235.6 and 301.5 ng g(-1) in the sheath, respectively, while they were 1051.1, 693.6 and 178.7 ng g(-1) in the lamina. The findings from pyrosequencing analysis of the rhizosphere bacteria suggest that the Dechloromonas sp., the Clostridium sp. (e.g. Clostridium saccharobutylicum), the order Sphingobacteriales, and the Cytophaga sp. in the order Cytophagales were most probably responsible for the rhizodegradation of ibuprofen. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Evaporation Behavior and Characterization of Eutectic Solvent and Ibuprofen Eutectic Solution.

    Science.gov (United States)

    Phaechamud, Thawatchai; Tuntarawongsa, Sarun; Charoensuksai, Purin

    2016-10-01

    Liquid eutectic system of menthol and camphor has been reported as solvent and co-solvent for some drug delivery systems. However, surprisingly, the phase diagram of menthol-camphor eutectic has not been reported previously. The evaporation behavior, physicochemical, and thermal properties of this liquid eutectic and ibuprofen eutectic solution were characterized in this study. Differential scanning calorimetry (DSC) analysis indicated that a eutectic point of this system was near to 1:1 menthol/camphor and its eutectic temperature was -1°C. The solubility of ibuprofen in this eutectic was 282.11 ± 6.67 mg mL(-1) and increased the drug aqueous solubility fourfold. The shift of wave number from Fourier transform infrared spectroscopy (FTIR) indicated the hydrogen bonding of each compound in eutectic mixture. The weight loss from thermogravimetric analysis of menthol and camphor related to the evaporation and sublimation, respectively. Menthol demonstrated a lower apparent sublimation rate than camphor, and the evaporation rate of eutectic solvent was lower than the sublimation rate of camphor but higher than the evaporation of menthol. The evaporation rate of the ibuprofen eutectic solution was lower than that of the eutectic solvent because ibuprofen did not sublimate. This eutectic solvent prolonged the ibuprofen release with diffusion control. Thus, the beneficial information for thermal behavior and related properties of eutectic solvent comprising menthol-camphor and ibuprofen eutectic solution was attained successfully. The rather low evaporation of eutectic mixture will be beneficial for investigation and tracking the mechanism of transformation from nanoemulsion into nanosuspension in the further study using eutectic as oil phase.

  2. Effects of ibuprofen on cognition and NMDA receptor subunit expression across aging.

    Science.gov (United States)

    Márquez Loza, Alejandra; Elias, Valerie; Wong, Carmen P; Ho, Emily; Bermudez, Michelle; Magnusson, Kathy R

    2017-03-06

    Age-related declines in long- and short-term memory show relationships to decreases in N-methyl-d-aspartate (NMDA) receptor expression, which may involve inflammation. This study was designed to determine effects of an anti-inflammatory drug, ibuprofen, on cognitive function and NMDA receptor expression across aging. Male C57BL/6 mice (ages 5, 14, 20, and 26months) were fed ibuprofen (375ppm) in NIH31 diet or diet alone for 6weeks prior to testing. Behavioral testing using the Morris water maze showed that older mice performed significantly worse than younger in spatial long-term memory, reversal, and short-term memory tasks. Ibuprofen enhanced overall performance in the short-term memory task, but this appeared to be more related to improved executive function than memory. Ibuprofen induced significant decreases over all ages in the mRNA densities for GluN2B subunit, all GluN1 splice variants, and GluN1-1 splice forms in the frontal cortex and in protein expression of GluN2A, GluN2B and GluN1 C2' cassettes in the hippocampus. GluN1-3 splice form mRNA and C2' cassette protein were significantly increased across ages in frontal lobes of ibuprofen-treated mice. Ibuprofen did not alter expression of pro-inflammatory cytokines IL-1β and TNFα, but did reduce the area of reactive astrocyte immunostaining in frontal cortex of aged mice. Enhancement in executive function showed a relationship to increased GluN1-3 mRNA and decreased gliosis. These findings suggest that inflammation may play a role in executive function declines in aged animals, but other effects of ibuprofen on NMDA receptors appeared to be unrelated to aging or inflammation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Pilot monitoring study of ibuprofen in surface waters of north of Portugal.

    Science.gov (United States)

    Paíga, Paula; Santos, Lúcia H M L M; Amorim, Célia G; Araújo, Alberto N; Montenegro, M Conceição B S M; Pena, Angelina; Delerue-Matos, Cristina

    2013-04-01

    Ibuprofen is amongst the most worldwide consumed pharmaceuticals. The present work presents the first data in the occurrence of ibuprofen in Portuguese surface waters, focusing in the north area of the country, which is one of the most densely populated areas of Portugal. Analysis of ibuprofen is based on pre-concentration of the analyte with solid phase extraction and subsequent determination with liquid chromatography coupled to fluorescence detection. A total of 42 water samples, including surface waters, landfill leachates, Wastewater Treatment Plant (WWTP), and hospital effluents, were analyzed in order to evaluate the occurrence of ibuprofen in the north of Portugal. In general, the highest concentrations were found in the river mouths and in the estuarine zone. The maximum concentrations found were 48,720 ng L(-1) in the landfill leachate, 3,868 ng L(-1) in hospital effluent, 616 ng L(-1) in WWTP effluent, and 723 ng L(-1) in surface waters (Lima river). Environmental risk assessment was evaluated and at the measured concentrations only landfill leachates reveal potential ecotoxicological risk for aquatic organisms. Owing to a high consumption rate of ibuprofen among Portuguese population, as prescribed and non-prescribed medicine, the importance of hospitals, WWTPs, and landfills as sources of entrance of pharmaceuticals in the environment was pointed out. Landfill leachates showed the highest contribution for ibuprofen mass loading into surface waters. On the basis of our findings, more studies are needed as an attempt to assess more vulnerable areas.

  4. Ibuprofen for acute treatment of episodic tension-type headache in adults.

    Science.gov (United States)

    Derry, Sheena; Wiffen, Philip J; Moore, R Andrew; Bendtsen, Lars

    2015-07-31

    Tension-type headache (TTH) affects about one person in five worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (1 to 14 headaches per month), and chronic TTH (15 headaches a month or more). Ibuprofen is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH. To assess the efficacy and safety of oral ibuprofen for treatment of acute episodic TTH in adults. We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, and our own in-house database to January 2015. We sought unpublished studies by asking personal contacts and searching on-line clinical trial registers and manufacturers' websites. We included randomised, placebo-controlled studies (parallel-group or cross-over) using oral ibuprofen for symptomatic relief of an acute episode of TTH. Studies had to be prospective and include at least 10 participants per treatment arm. Two review authors independently assessed studies for inclusion, and extracted data. Numbers of participants achieving each outcome were used to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or number needed to treat for an additional harmful outcome (NNH) of oral ibuprofen compared to placebo for a range of outcomes, predominantly those recommended by the International Headache Society (IHS). We included 12 studies, all of which enrolled adult participants with frequent episodic TTH. Nine used the IHS diagnostic criteria, but two used the older classification of the Ad Hoc Committee, and one did not describe diagnostic criteria but excluded participants with migraines. While 3094 people with TTH participated in these studies, the numbers available for any form of analysis were lower than this; placebo was taken by 733, standard ibuprofen 200 mg by 127, standard ibuprofen 400 mg by 892, and fast-acting ibuprofen 400 mg by 230. Participants had moderate or severe pain at the start of

  5. Enantioselective analysis of ibuprofen and its biotransformation products in water/sediment systems,

    DEFF Research Database (Denmark)

    Sundström, Maria; Escola, Monica; Radke, Michael

    2015-01-01

    of the sediments in the aquatic systems has neither been taken in account previously. In this study, four water-sediment systems were chosen according to anthropogenic exposure and sediment conditions. A low anthropogenic impact lake (Largen), a river receiving wastewater (Fyrisån) and two sediments (anoxic......As ibuprofen degrades enantioselectively in activated sludge, the same process is assumed to occur in surface lake-water and in river-water based biofilms. Yet, the effects of the wastewater inflow, containing non-racemic ibuprofen, into natural systems have never been studied. The role......-7 days in Tvären and B1 respectively. Largen sediments, not impacted by wastewater, degraded ibuprofen faster than Fyrisån sediments did. Yet, these two sediments sediments showed no significant difference with respect to the degradation rates of the ibuprofen enantiomers. A connection between wastewater...

  6. Akut pankreatitis hos en 16-årig dreng efter indtag af ibuprofen

    DEFF Research Database (Denmark)

    Bruusgaard-Mouritsen, Mads Emil; Leerhøy, Bonna; Hansen, Mark Berner

    2015-01-01

    This is a case report of a 16-year-old boy with possible drug-induced pancreatitis (DIP) caused by ibuprofen. The patient had a history of psychiatric, but no somatic, disease, and he was admitted with a clinical presentation consistent with acute pancreatitis after a bolus ingestion of 10 g...... of ibuprofen in a suicidal attempt. No evidence of other causality for acute pancreatitis was identified. The patient was treated with a standard pancreatitis treatment regime and was discharged against medical advice after four days. The case represents a possible causality between ibuprofen and DIP....

  7. Impregnation of Ibuprofen into Polycaprolactone using supercritical carbon dioxide

    International Nuclear Information System (INIS)

    Yoganathan, Roshan; Mammucari, Raffaella; Foster, Neil R

    2010-01-01

    Polycaprolactone (PCL) is a Food and Drug Administration (FDA) approved biodegradable polyester used in tissue engineering applications. Ibuprofen is an anti-inflammatory drug which has good solubility in supercritical CO 2 (SCCO 2 ). The solubility of CO 2 in PCL allows for the impregnation of CO 2 -soluble therapeutic agents into the polymer via a supercritical fluid (SCF) process. Polymers impregnated with bio-active compounds are highly desired for medical implants and controlled drug delivery. In this study, the use of CO 2 to impregnate PCL with ibuprofen was investigated. The effect of operating conditions on the impregnation of ibuprofen into PCL was investigated over two pressure and two temperature levels, 150bar and 200bar, 35 0 C and 40 0 C, respectively. Polycaprolactone with drug-loadings as high as 27% w/w were obtained. Impregnated samples exhibited controlled drug release profiles over several days.

  8. Efficacy and safety of rectal ibuprofen for patent ductus arteriosus closure in very low birth weight preterm infants.

    Science.gov (United States)

    Demir, Nihat; Peker, Erdal; Ece, İbrahim; Balahoroğlu, Ragıp; Tuncer, Oğuz

    2017-09-01

    To compare rectal ibuprofen with oral ibuprofen for the closure of hemodynamically significant patent ductus arteriosus (hsPDA) in very low birth weight (VLBW) preterm infants. In a prospective, randomized study, 72 VLBW infants who had hsPDA received either rectal or oral ibuprofen. The plasma concentration of ibuprofen and renal functions were determined in both groups by the high-performance liquid chromatography (HPLC) method and cystatin-C (cys-C), respectively. The hsPDA closure rate of the group that received rectal ibuprofen was similar to oral ibuprofen (86.1% versus 83.3%) after the first course of the treatment (p = 0.745). A statistically significant difference was identified between the mean plasma cys-C levels before and after treatment in both the rectal and oral ibuprofen groups (p = 0.004 and p 0.05 for all values). Rectal ibuprofen is as effective as oral ibuprofen for hsPDA closure in VLBW infants. The rise in the cys-C level with rectal and oral treatment shows that patients with borderline renal function should be evaluated and followed closely.

  9. Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.

    Science.gov (United States)

    Karlsson, Jessica; Fowler, Christopher J

    2014-01-01

    In addition to their effects upon prostaglandin synthesis, the non-steroidal anti-inflammatory drugs ibuprofen and flurbiprofen inhibit the metabolism of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) by cyclooxygenase-2 (COX-2) and fatty acid amide hydrolase (FAAH), respectively. Here, we investigated whether these effects upon endocannabinoid metabolism are shared by the main metabolites of ibuprofen and flurbiprofen. COX activities were measured via changes in oxygen consumption due to oxygenation of arachidonic acid (for COX-1) and arachidonic acid and 2-AG (for COX-2). FAAH activity was quantified by measuring hydrolysis of tritium labelled AEA in rat brain homogenates. The ability of ibuprofen and flurbiprofen to inhibit COX-2-catalysed oxygenation of 2-AG at lower concentrations than the oxygenation of arachidonic acid was seen with 4'-hydroxyflurbiprofen and possibly also 3'-hydroxyibuprofen, albeit at lower potencies than the parent compounds. All ibuprofen and flurbiprofen metabolites retained the ability to inhibit FAAH in a pH-dependent manner, although the potency was lower than seen with the parent compounds. It is concluded that the primary metabolites of ibuprofen and flurbiprofen retain some of the properties of the parent compound with respect to inhibition of endocannabinoid metabolism. However, these effects are unlikely to contribute to the actions of the parent compounds in vivo.

  10. Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.

    Directory of Open Access Journals (Sweden)

    Jessica Karlsson

    Full Text Available In addition to their effects upon prostaglandin synthesis, the non-steroidal anti-inflammatory drugs ibuprofen and flurbiprofen inhibit the metabolism of the endocannabinoids 2-arachidonoylglycerol (2-AG and anandamide (AEA by cyclooxygenase-2 (COX-2 and fatty acid amide hydrolase (FAAH, respectively. Here, we investigated whether these effects upon endocannabinoid metabolism are shared by the main metabolites of ibuprofen and flurbiprofen.COX activities were measured via changes in oxygen consumption due to oxygenation of arachidonic acid (for COX-1 and arachidonic acid and 2-AG (for COX-2. FAAH activity was quantified by measuring hydrolysis of tritium labelled AEA in rat brain homogenates. The ability of ibuprofen and flurbiprofen to inhibit COX-2-catalysed oxygenation of 2-AG at lower concentrations than the oxygenation of arachidonic acid was seen with 4'-hydroxyflurbiprofen and possibly also 3'-hydroxyibuprofen, albeit at lower potencies than the parent compounds. All ibuprofen and flurbiprofen metabolites retained the ability to inhibit FAAH in a pH-dependent manner, although the potency was lower than seen with the parent compounds.It is concluded that the primary metabolites of ibuprofen and flurbiprofen retain some of the properties of the parent compound with respect to inhibition of endocannabinoid metabolism. However, these effects are unlikely to contribute to the actions of the parent compounds in vivo.

  11. Ibuprofen and Diclofenac Restrict Migration and Proliferation of Human Glioma Cells by Distinct Molecular Mechanisms

    Science.gov (United States)

    Leidgens, Verena; Seliger, Corinna; Jachnik, Birgit; Welz, Tobias; Leukel, Petra; Vollmann-Zwerenz, Arabel; Bogdahn, Ulrich; Kreutz, Marina; Grauer, Oliver M.; Hau, Peter

    2015-01-01

    Background Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with anti-tumorigenic effects in different tumor entities. For glioma, research has generally focused on diclofenac; however data on other NSAIDs, such as ibuprofen, is limited. Therefore, we performed a comprehensive investigation of the cellular, molecular, and metabolic effects of ibuprofen and diclofenac on human glioblastoma cells. Methods Glioma cell lines were treated with ibuprofen or diclofenac to investigate functional effects on proliferation and cell motility. Cell cycle, extracellular lactate levels, lactate dehydrogenase-A (LDH-A) expression and activity, as well as inhibition of the Signal Transducer and Activator of Transcription 3 (STAT-3) signaling pathway, were determined. Specific effects of diclofenac and ibuprofen on STAT-3 were investigated by comparing their effects with those of the specific STAT-3 inhibitor STATTIC. Results Ibuprofen treatment led to a stronger inhibition of cell growth and migration than treatment with diclofenac. Proliferation was affected by cell cycle arrest at different checkpoints by both agents. In addition, diclofenac, but not ibuprofen, decreased lactate levels in all concentrations used. Both decreased STAT-3 phosphorylation; however, diclofenac led to decreased c-myc expression and subsequent reduction in LDH-A activity, whereas treatment with ibuprofen in higher doses induced c-myc expression and less LDH-A alteration. Conclusions This study indicates that both ibuprofen and diclofenac strongly inhibit glioma cells, but the subsequent metabolic responses of both agents are distinct. We postulate that ibuprofen may inhibit tumor cells also by COX- and lactate-independent mechanisms after long-term treatment in physiological dosages, whereas diclofenac mainly acts by inhibition of STAT-3 signaling and downstream modulation of glycolysis. PMID:26485029

  12. Effects of diclofenac and celecoxib on osteoclastogenesis during alveolar bone healing, in vivo

    Directory of Open Access Journals (Sweden)

    Parichehr Ghalayani

    2014-01-01

    Full Text Available Background: Osteoclastogenesis is coordinated by the interaction of members of the tumor necrosis factor (TNF superfamily: Receptor activator of nuclear factor- κB ligand (RANKL and Osteoprotegerin (OPG. The aim of this study was to compare the effect of two different types of non-steroidal anti-inflammatory drugs (NSAIDs on the RANKL/OPG balance during the healing of the alveolar process. Materials and Methods: This was an experimental study, carried on 45 male Wistar rats (200 ± 25 g, 8-10 weeks old. After extraction of the right maxillary first molar, 15 rats received 5 mg/kg/day of diclofenac and 15 rats received 15 mg/kg/day of celecoxib and 15 rats received normal saline. The animals were sacrificed 7, 14 and 21 days after tooth extraction. The number of osteoclasts, OPG and RANKL messenger ribonucleic acid expression were determined by tartrate-resistant acid phosphate (TRAP staining and polymerase chain reaction (PCR respectively. The data were analyzed by one-way ANOVA followed by Tukey′s post-hoc test. Values of P < 0.05 were considered significant. Results: On days 7, 14 and 21 the ratio of RANKL/OPG in the control group was higher than diclofenac and celecoxib groups. TRAP immunolabeling of the control group was more than diclofenac group on day 7 and was more than celecoxib group on day 14. On day 21, no significant differences were noted among the three studied groups. Conclusion: Both drugs affect RANKL/OPG gene expression and also osteoclastogenesis in alveolar socket during the experimental period of 21 days.

  13. Phospho-Ibuprofen (MDC-917) Is a Novel Agent against Colon Cancer: Efficacy, Metabolism, and Pharmacokinetics in Mouse Models

    Science.gov (United States)

    Xie, Gang; Sun, Yu; Nie, Ting; Mackenzie, Gerardo G.; Huang, Liqun; Kopelovich, Levy; Komninou, Despina

    2011-01-01

    We have developed a novel chemical modification of conventional nonsteroidal anti-inflammatory drugs to reduce their toxicity and enhance their efficacy. Phospho-ibuprofen [(PI) 2-(4-isobutyl-phenyl)-propionic acid-4-(diethoxy-phosphoryloxy)-butyl ester (MDC-917)], a novel derivative of ibuprofen, strongly inhibited the growth of human colon cancer cells in vitro and SW480 human colon cancer xenografts in nude mice. PI was metabolized minimally by cultured cells, but extensively by liver microsomes and mice, undergoing regioselective oxidation to produce 1-OH-PI and carboxyl-PI, which can be hydrolyzed to 1-OH-ibuprofen and carboxyl-ibuprofen, respectively. PI also can be hydrolyzed to release ibuprofen, which can generate 2-OH-ibuprofen, carboxyl-ibuprofen, and ibuprofen glucuronide. After a single oral administration (400 mg/kg) of PI, ibuprofen and ibuprofen glucuronide are the main plasma metabolites of PI; they have, respectively, Cmax of 530 and 215 μM, Tmax of 1 and 2 h, elimination t1/2 of 7.7 and 5.3 h, and area under the concentration-time curve (0–24 h) of 1816 and 832 μM × h. Intact PI was detected in several tissues but not in plasma; at a higher PI dose (1200 mg/kg), PI plasma levels were 12.4 μM. PI generated the same metabolites in mouse plasma as conventional ibuprofen, but with much lower levels, perhaps accounting for the enhanced safety of PI. The antitumor effect of PI was significantly associated with plasma ibuprofen levels (p = 0.016) but not with xenograft ibuprofen levels (p = 0.08), suggesting a complex anticancer effect. These results provide a pharmacological basis to explain, at least in part, the anticancer efficacy and safety of this promising compound and indicate that PI merits further evaluation as an anticancer agent. PMID:21422165

  14. Celecoxib Ameliorates Non-Alcoholic Steatohepatitis in Type 2 Diabetic Rats via Suppression of the Non-Canonical Wnt Signaling Pathway Expression

    Science.gov (United States)

    Tian, Feng; Zhang, Ya Jie; Li, Yu; Xie, Ying

    2014-01-01

    Our aim was to test whether pharmacological inhibition of cycloxygenase-2 (COX-2) reverses non-alcoholic steatohepatitis (NASH) in type 2 diabetes mellitus (T2DM) rats via suppression of the non-canonical Wnt signaling pathway expression. Twenty-four male Sprague-Dawley rats were randomly distributed to two groups and were fed with a high fat and sucrose (HF-HS) diet or a normal chow diet, respectively. After four weeks, rats fed with a HF-HS diet were made diabetic with low-dose streptozotocin. At the 9th week the diabetic rats fed with a HF-HS diet or the non-diabetic rats fed with a normal chow diet were further divided into two subgroups treated with vehicle or celecoxib (a selective COX-2 inhibitor, 10 mg/Kg/day, gavage) for the last 4 weeks, respectively. At the end of the 12th week, rats were anesthetized. NASH was assessed by histology. Related cytokine expression was measured at both the protein and gene levels through immunohistochemistry (IHC), Western blot and real-time PCR. T2DM rats fed with a HF-HS diet developed steatohepatitis and insulin resistance associated with elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin levels and the non-alcoholic fatty liver disease (NAFLD) activity score (NAS). The expression of Wnt5a, JNK1, NF-κB p65, and COX-2 were all significantly increased in the T2DM-NASH group compared with the control and control-cele group. Hepatic injury was improved by celecoxib in T2DM-NASH-Cele group indicated by reduced serum ALT and AST levels and hepatic inflammation was reduced by celecoxib showed by histology and the NAFLD activity score (NAS). Serum related metabolic parameters, HOMA-IR and insulin sensitivity index were all improved by celecoxib. The expression of Wnt5a, JNK1, NF-κB p65, and COX-2 expression were all suppressed by celecoxib in T2DM-NASH-Cele group. The results of the present study indicated that celecoxib ameliorated NASH in T2DM rats via suppression of the non-canonical Wnt

  15. Spectral Analyses of a Novel Ibuprofen-Phillygenin Ester

    Directory of Open Access Journals (Sweden)

    FAN Hong-yu

    2018-03-01

    Full Text Available An ibuprofen-phillygenin ester was synthesized through the Schotten-Baumann reaction with ibuprofen and phillygenin as the starting materials. Ultraviolet absorption (UV spectrum, infrared absorption (IR spectrum, matrix-assisted laser desorption/ionization-mass spectra (MALDI-TOF-MS, and one-dimensional/two dimensional nuclear magnetic resonance (NMR spectra (i.e., 1H-NMR, 13C-NMR, 13C-DEPT, 1H-1H COSY, 1H-1H NOESY, 1H-13C HSQC and 1H-13C HMBC of the compound were collected. All 1H and 13C NMR signals were assigned.

  16. Effects of acetaminophen and ibuprofen in children with migraine receiving preventive treatment with magnesium.

    Science.gov (United States)

    Gallelli, Luca; Avenoso, Tiziana; Falcone, Daniela; Palleria, Caterina; Peltrone, Francesco; Esposito, Maria; De Sarro, Giovambattista; Carotenuto, Marco; Guidetti, Vincenzo

    2014-02-01

    The purpose of this study was to evaluate both the effects of ibuprofen and/or acetaminophen for the acute treatment of primary migraine in children in or out prophylactic treatment with magnesium. Children ranging from the ages of 5 to 16 years with at least 4 attack/month of primary migraine were eligible for participation the study. A visual analog scale was used to evaluate pain intensity at the moment of admission to the study (start of the study) and every month up to 18 months later (end of the study). One hundred sixty children of both sexes aged 5-16 years were enrolled and assigned in 4 groups to receive a treatment with acetaminophen or ibuprofen without or with magnesium. Migraine pain endurance and monthly frequency were similar in the 4 groups. Both acetaminophen and ibuprofen induced a significant decrease in pain intensity (P < .01), without a time-dependent correlation, but did not modify its frequency. Magnesium pretreatment induced a significant decrease in pain intensity (P < .01) without a time-dependent correlation in both acetaminophen- and ibuprofen-treated children and also significantly reduced (P < .01) the pain relief timing during acetaminophen but not during ibuprofen treatment (P < .01). In both acetaminophen and ibuprofen groups, magnesium pretreatment significantly reduced the pain frequency (P < .01). Magnesium increased the efficacy of ibuprofen and acetaminophen with not age-related effects. © 2013 American Headache Society.

  17. Impregnation of Ibuprofen into Polycaprolactone using supercritical carbon dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Yoganathan, Roshan; Mammucari, Raffaella; Foster, Neil R, E-mail: n.foster@unsw.edu.a [Supercritical Fluids Research Group, School of Chemical Sciences and Engineering, University of New South Wales, NSW 2052 (Australia)

    2010-03-01

    Polycaprolactone (PCL) is a Food and Drug Administration (FDA) approved biodegradable polyester used in tissue engineering applications. Ibuprofen is an anti-inflammatory drug which has good solubility in supercritical CO{sub 2} (SCCO{sub 2}). The solubility of CO{sub 2} in PCL allows for the impregnation of CO{sub 2}-soluble therapeutic agents into the polymer via a supercritical fluid (SCF) process. Polymers impregnated with bio-active compounds are highly desired for medical implants and controlled drug delivery. In this study, the use of CO{sub 2} to impregnate PCL with ibuprofen was investigated. The effect of operating conditions on the impregnation of ibuprofen into PCL was investigated over two pressure and two temperature levels, 150bar and 200bar, 35{sup 0}C and 40 {sup 0}C, respectively. Polycaprolactone with drug-loadings as high as 27% w/w were obtained. Impregnated samples exhibited controlled drug release profiles over several days.

  18. Efficacy of ibuprofen on prevention of high altitude headache: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Juan Xiong

    Full Text Available Ibuprofen is used to prevent high altitude headache (HAH but its efficacy remains controversial. We conducted a systematic review and meta-analysis of randomized, placebo-controlled trials (RCTs of ibuprofen for the prevention of HAH.Studies reporting efficacy of ibuprofen for prevention of HAH were identified by searching electronic databases (until December 2016. The primary outcome was the difference in incidence of HAH between ibuprofen and placebo groups. Risk ratios (RR were aggregated using a Mantel-Haenszel random effect model. Heterogeneity of included trials was assessed using the I2 statistics.In three randomized-controlled clinical trials involving 407 subjects, HAH occurred in 101 of 239 subjects (42% who received ibuprofen and 96 of 168 (57% who received placebo (RR = 0.79, 95% CI 0.66 to 0.96, Z = 2.43, P = 0.02, I2 = 0%. The absolute risk reduction (ARR was 15%. Number needed to treat (NNT to prevent HAH was 7. Similarly, The incidence of severe HAH was significant in the two groups (RR = 0.40, 95% CI 0.17 to 0.93, Z = 2.14, P = 0.03, I2 = 0%. Severe HAH occurred in 3% treated with ibuprofen and 10% with placebo. The ARR was 8%. NNT to prevent severe HAH was 13. Headache severity using a visual analogue scale was not different between ibuprofen and placebo. Similarly, the difference between the two groups in the change in SpO2 from baseline to altitude was not different. One included RCT reported one participant with black stools and three participants with stomach pain in the ibuprofen group, while seven participants reported stomach pain in the placebo group.Based on a limited number of studies ibuprofen seems efficacious for the prevention of HAH and may therefore represent an alternative for preventing HAH with acetazolamide or dexamethasone.

  19. Ibuprofen-loaded poly(lactic-co-glycolic acid films for controlled drug release

    Directory of Open Access Journals (Sweden)

    Pang JM

    2011-04-01

    Full Text Available Jianmei Pang1, Yuxia Luan1, Feifei Li1, Xiaoqing Cai1, Jimin Du2, Zhonghao Li31School of Pharmaceutical Science, Shandong University, Jinan, Shandong Province, PR China; 2School of Chemistry and Chemical Engineering, Anyang Normal University, Henan Province, PR China; 3School of Materials Science and Engineering, Shandong University, Jinan, Shandong Province, PR ChinaAbstract: Ibuprofen- (IBU loaded biocompatible poly(lactic-co-glycolic acid (PLGA films were prepared by spreading polymer/ibuprofen solution on the nonsolvent surface. By controlling the weight ratio of drug and polymer, different drug loading polymer films can be obtained. The synthesized ibuprofen-loaded PLGA films were characterized with scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. The drug release behavior of the as-prepared IBU-loaded PLGA films was studied to reveal their potential application in drug delivery systems. The results show the feasibility of the as-obtained films for controlling drug release. Furthermore, the drug release rate of the film could be controlled by the drug loading content and the release medium. The development of a biodegradable ibuprofen system, based on films, should be of great interest in drug delivery systems.Keywords: ibuprofen, controlled release, poly(lactic-co-glycolic acid, films

  20. Omeprazole and misoprostol for preventing gastric mucosa effects caused by indomethacin and celecoxib in rats Omeprazol e misoprostol na prevenção de lesões de mucosa gástrica causadas por indometacina e celecoxib em ratos

    Directory of Open Access Journals (Sweden)

    Míriam Elias Cavallini

    2006-06-01

    Full Text Available PURPOSE: To evaluate and to compare macro and microscopically the intense injuries of the gastric mucosa of rats which were caused by NSAIDS celecoxib and indomethacin and the gastric cytoprotection with omeprazole and misoprostol. METHODS: The sample is formed by one hundred and fifty Wistar rats with average weight 200 g, distributed in four groups, such as: Group A, subdivided in groups A1 and A2 - pre-treatment with omeprazole (20 mg/rat during seven days and on the 8th day - use of NSAIDS, concerning A1 (20 rats were given celecoxib (1mg/rat and A2 (20 rats were given indomethacin. The Group B, subdivided in group B1 and B2 - pre-treatment with misoprostol (20mg/rat during seven days and on the 8th day use of NSAIDS, concerning B1 (20 rats were given celecoxib (1 mg/ rat and B2 (20 rats were given indomethacin (12.5 mg/rat. The Group C: were not given cytoprotection during seven days, from the 7th to the 8th day - fast of food and water ad libitum, on the 8th day of NSAIDS use, concerning C1 (20 rats were given celecoxib, C2 (20 rats were given indomethacin (12.5 mg/ rat, C3 (20 rats were given celecoxib (200mg/rato, and Group D - control group, concerning 10 rats were observed during seven days ingesting food and water ad libitum. On the 9th day, the stomachs were taken out and were macro and microscopically evaluated for the identification of the gastric injuries. RESULTS: On the macroscopic studies, the groups A2, B2 and C2 presented a remarkable high number of injuries for cm² /animal, respectively 18.55 injuries for cm² /animal, 16.25 injuries for cm² /animal and 13.55 injuries for cm²/animal. On the microscopic studies, the percentage of the injured mucosa, presented expressive difference among the groups A1, B1, C1 when compared to the groups A2, B2, C2 (pOBJETIVO: Avaliar e comparar macro e microscopicamente as lesões agudas da mucosa gástrica de ratos provocadas pelos AINEs celecoxib e indometacina e a citoproteção g

  1. Role of GSK-3β in Regulation of Canonical Wnt/β-catenin Signaling and PI3-K/Akt Oncogenic Pathway in Colon Cancer.

    Science.gov (United States)

    Jain, Shelly; Ghanghas, Preety; Rana, Chandan; Sanyal, S N

    2017-08-09

    Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents because of their ability in blocking cellular proliferation, and thereby tumor development, and also by promoting apoptosis. GSK-3β, a serine threonine kinase and a negative regulator of the oncogenic Wnt/β-catenin signaling pathway, plays a critical role in the regulation of oncogenesis. Celecoxib and etoricoxib, the two cyclooxygenase-2 (COX-2) selective NSAIDs, and Diclofenac, a preferential COX-2 inhibitory NSAID, had shown uniformly the chemopreventive and anti-neoplastic effects in the early stage of colon cancer by promoting apoptosis as well as an over-expression of GSK-3β while down-regulating the PI3-K/Akt oncogenic pathway.

  2. Ibuprofen Release from Poly(ethyl cyanoacrylate Nanoparticles Prepared by Semicontinuous Heterophase Polymerization

    Directory of Open Access Journals (Sweden)

    J. A. Balleño

    2018-01-01

    Full Text Available Ibuprofen-loaded poly(ethyl cyanoacrylate nanoparticles were prepared by semicontinuous heterophase polymerization of ethyl cyanoacrylate in the presence of ibuprofen; different surfactant concentration, pH, and temperature were used. Particle size was measured by quasi-light scattering and transmission electron microscopy, while the amount of drug released was determined by UV spectroscopy. Nanoparticles with diameters between 10 and 58 nm, loaded with ibuprofen, were obtained. The smallest particles and the higher drug loading were obtained at the highest pH tested. The analysis of the release data showed that the drug release profiles correspond to the Weibull model. Moreover, it was found that most of the ibuprofen is released within the first 80–120 min; initially the release rate is slow, but then it increases to finally decrease. This behavior contrasts with the reported burst of drug concentration in the plasma after oral administration of IB.

  3. Mucoadhesive microemulsion of ibuprofen: design and evaluation for brain targeting efficiency through intranasal route

    Directory of Open Access Journals (Sweden)

    Surjyanarayan Mandal

    2015-09-01

    Full Text Available This study aimed at designing mucoadhesive microemulsion gel to enhance the brain uptake of Ibuprofen through intranasal route. Ibuprofen loaded mucoadhesive microemulsion (MMEI was developed by incorporating polycarbophil as mucoadhesive polymer into Capmul MCM based optimal microemulsion (MEI and was subjected to characterization, stability, mucoadhesion and naso-ciliotoxicity study. Brain uptake of ibuprofen via nasal route was studied by performing biodistribution study in Swiss albino rats. MEI was found to be transparent, stable and non ciliotoxic with 66.29 ± 4.15 nm, -20.9 ± 3.98 mV and 98.66 ± 1.01% as average globule size, zeta potential and drug content respectively. Transmission Electron Microscopy (TEM study revealed the narrow globule size distribution of MEI. Following single intranasal administration of MMEI and MEI at a dose of 2.86 mg/kg, uptake of ibuprofen in the olfactory bulb was around 3.0 and 1.7 folds compared with intravenous injection of ibuprofen solution (IDS. The ratios of AUC in brain tissues to that in plasma obtained after nasal administration of MMEI were significantly higher than those after intravenous administration of IDS. Findings of the present investigation revealed that the developed mucoadhesive microemulsion gel could be a promising approach for brain targeting of ibuprofen through intranasal route.

  4. Gastroprotective effects of several H2RAs on ibuprofen-induced gastric ulcer in rats.

    Science.gov (United States)

    Liu, Jing; Sun, Dan; He, Jinfeng; Yang, Chengli; Hu, Tingting; Zhang, Lijing; Cao, Hua; Tong, Ai-Ping; Song, Xiangrong; Xie, Yongmei; He, Gu; Guo, Gang; Luo, Youfu; Cheng, Ping; Zheng, Yu

    2016-03-15

    Ibuprofen is the first line of treatment for osteoarthritis and arthritis. The main side effects of ibuprofen especially in long-term treatment include gastric ulcer, duodenal ulcer and indigestion etc. Therefore, screening drugs with effective gastric protective effects and low toxicity for combination therapy with ibuprofen is necessary. The mechanism of gastric damage induced by ibuprofen is still unclear, however, cell damage caused by reactive oxygen species (ROS) is considered as the main reason. Preliminary screening of literature with the criteria of low toxicity led to four histamine-2 receptor antagonists (H2RAs): nizatidine, famotidine, lafutidine, and roxatidine acetate, which were selected for further investigation. These drugs were evaluated systemically by examining the gastric ulcer index, lipid peroxidation (LPO), membrane permeability, toxicity to main organs, and the influence on the activity of antioxidant enzymes, and myeloperoxidase (MPO). Nizatidine was found to be the best gastric protective agent. It exhibited excellent protective effect by increasing antioxidant enzyme activity, decreasing MPO activity, reducing LPO, and membrane permeability. Combination treatment with nizatidine and ibuprofen did not show any significant toxicity. Nizatidine was considered as a good option for combination therapy with ibuprofen especially for diseases that require long-term treatment such as arthritis and osteoarthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Effects of Ibuprofen on the physiology and outcome of rabbit endotoxic shock

    Directory of Open Access Journals (Sweden)

    Canbaz Mukaddes

    2002-10-01

    Full Text Available Abstract Background Despite major developments in the management of septic shock, the mortality rate had progressively increased. Ibuprofen has been shown to have beneficial physiological effects when used as a treatment. However, there are conflicting results with respect to survival. This study aims to investigate the effect of ibuprofen on vital functions, various physiological parameters and survival during endotoxic shock in rabbits. Methods Twenty-eight New Zealand rabbits were randomly separated into four groups. The first group received only saline, the second was given 2 mg/kg intravenous endotoxin at t0, the third received 30 mg/kg ibuprofen 30 minutes after endotoxin administration, whilst the fourth group received ibuprofen 30 minutes before the endotoxin. Respiratory and heart rate, mean arterial blood pressure and rectal temperature were recorded. Complete blood counts were performed and thromboxane B2 was measured every 30 minutes for the first two hours, and then hourly over the course of the experiment. Urine samples were collected at the same time points for the measurement of prostaglandin E2. Results Ibuprofen was found to improve respiratory rate, heart rate, and arterial pressure. However, it did not improve the negative effects of endotoxin on body temperature, haematocrit values, white blood cell count, and thrombocyte number. Thromboxane B2 levels in group IV were significantly lower than in the other groups, and the increase started at a later timepoint. In ibuprofen-treated animals, Prostaglandin E2 levels stayed low for at least 90 minutes, but started to rise thereafter. While the average survival in Group II animals was 192.9 ± 46.9 minutes, those of groups III and IV were 339.1 ± 33.5 minutes (p Conclusions Ibuprofen appears to increase survival in endotoxic shock-induced animals. Therefore, it may be helpful for the prophylaxis and treatment of patients with, or who are likely to develop, septic shock.

  6. Disposable screen printed graphite electrode for the direct electrochemical determination of ibuprofen in surface water

    KAUST Repository

    Amin, Sidra; Soomro, M. Tahir; Memon, Najma; Solangi, Amber R.; Sirajuddin; Qureshi, Tahira; Behzad, Ali Reza

    2014-01-01

    The potential of square wave voltammetry (SWV) for the determination of ibuprofen in aqueous solution, applying baseline correction, is reported. A screen printed graphite electrodes (SPGEs), especially pretreated for this purpose, were used to investigate the electrochemical oxidation and detection of ibuprofen. After optimization of SWV parameters, measurements were carried out at 200 Hz modulation frequency, 4 mV step potential and 40 mV pulse amplitude for the determination of ibuprofen. The surfaces of both untreated and pretreated SPGEs were characterized by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). The electro-catalytic properties of both the electrodes were correlated with the surface treatment. The pretreated screen printed graphite electrode exhibited a high sensitivity toward ibuprofen even in low concentration. The developed method was found rapid, cost-effective and reproducible for in-field ibuprofen detection.

  7. Disposable screen printed graphite electrode for the direct electrochemical determination of ibuprofen in surface water

    KAUST Repository

    Amin, Sidra

    2014-08-01

    The potential of square wave voltammetry (SWV) for the determination of ibuprofen in aqueous solution, applying baseline correction, is reported. A screen printed graphite electrodes (SPGEs), especially pretreated for this purpose, were used to investigate the electrochemical oxidation and detection of ibuprofen. After optimization of SWV parameters, measurements were carried out at 200 Hz modulation frequency, 4 mV step potential and 40 mV pulse amplitude for the determination of ibuprofen. The surfaces of both untreated and pretreated SPGEs were characterized by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). The electro-catalytic properties of both the electrodes were correlated with the surface treatment. The pretreated screen printed graphite electrode exhibited a high sensitivity toward ibuprofen even in low concentration. The developed method was found rapid, cost-effective and reproducible for in-field ibuprofen detection.

  8. Alternating ibuprofen and acetaminophen in the treatment of febrile children: a pilot study [ISRCTN30487061

    Directory of Open Access Journals (Sweden)

    Sabra Ramzi

    2006-03-01

    Full Text Available Abstract Background Alternating ibuprofen and acetaminophen for the treatment of febrile children is a prevalent practice among physicians and parents, despite the lack of evidence on effectiveness or safety. This randomized, double-blind and placebo-controlled clinical trial aims at comparing the antipyretic effectiveness and safety of a single administration of alternating ibuprofen and acetaminophen doses to that of ibuprofen mono-therapy in febrile children. Methods Seventy febrile children were randomly allocated to receive either a single oral dose of 10 mg/kg ibuprofen and 15 mg/kg oral acetaminophen after 4 hours, or a similar dose of ibuprofen and placebo at 4 hours. Rectal temperature was measured at baseline, 4, 5, 6, 7 and 8 hours later. Endpoints included proportions of afebrile children at 6, 7 and 8 hours, maximum decline in temperature, time to recurrence of fever, and change in temperature from baseline at each time point. Intent-to-treat analysis was planned with statistical significance set at P Results A higher proportion of subjects in the intervention group (83.3% became afebrile at 6 hours than in the control group (57.6%; P = 0.018. This difference was accentuated at 7 and 8 hours (P Conclusion A single dose of alternating ibuprofen and acetaminophen appears to be a superior antipyretic regimen than ibuprofen mono-therapy. Further studies are needed to confirm these findings.

  9. Characteristics and clinical implications of the pharmacokinetic profile of ibuprofen in patients with knee osteoarthritis.

    Science.gov (United States)

    Gallelli, L; Galasso, O; Urzino, A; Saccà, S; Falcone, D; Palleria, C; Longo, P; Corigliano, A; Terracciano, R; Savino, R; Gasparini, G; De Sarro, G; Southworth, S R

    2012-12-01

    Ibuprofen is a non-selective cyclo-oxygenase (COX)-1/COX-2 inhibitor used to treat pain conditions and inflammation. Limited data have been published concerning the pharmacokinetic profile and clinical effects of ibuprofen in patients with osteoarthritis (OA). In this paper we compared the pharmacokinetic and clinical profile of ibuprofen (at a dosage of from 800 mg/day to 1800 mg/day) administered in patients affected by severe knee OA. Ibuprofen was administered for 7 days to patients who were scheduled to undergo knee arthroplasty due to OA. After 7 days, the ibuprofen concentration in plasma and synovial fluid was measured through both high-performance liquid chromatography (HPLC)-UV and gas chromatography-mass spectroscopy (GC/MS), while clinical effects were evaluated through both visual analogue scale (VAS) and Western Ontario and McMaster Universities (WOMAC) scores. The Naranjo scale and the WHO causality assessment scale were used for estimating the probability of adverse drug reactions (ADRs). The severity of ADRs was assessed by the modified Hartwig and Siegel scale. Ibuprofen showed a dose-dependent diffusion in both plasma and synovial fluid, which was related to the reduction of pain intensity and improvement of health status, without the development of ADRs. Ibuprofen at higher dosages can be expected to provide better control of OA symptoms as a result of higher tissue distribution.

  10. Layered zinc hydroxide–ibuprofen nanohybrids: synthesis and ...

    Indian Academy of Sciences (India)

    The nonsteroidal anti-inflammatory drug (NSAID), ibuprofen (IBU) anion, was intercalated into the layered zinc ... surface morphology, Fourier transform infrared (FTIR) spectrophotometer to study the chemical interactions and ..... J. Food Sci.

  11. Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Rasmussen, Jeppe Nørgaard; Abildstrøm, Steen Zabell

    2009-01-01

    .58-1.82), 1.75 (1.63-1.88), 1.31 (1.25-1.37), 2.08 (1.95-2.21), 1.22 (1.07-1.39), and 1.28 (1.21-1.35) for rofecoxib, celecoxib, ibuprofen, diclofenac, naproxen, and other NSAIDs, respectively. Furthermore, there was a dose-dependent increase in risk of death and increased risk of hospitalization because...

  12. Ongoing treatment with non-steroidal anti-inflammatory drugs at time of admission is associated with poorer prognosis in patients with first-time acute myocardial infarction

    DEFF Research Database (Denmark)

    Lamberts, Morten; Fosbøl, Emil L; Olsen, Anne-Marie S

    2013-01-01

    was significantly increased in patients receiving rofecoxib (hazard ratio [HR] 1.15; CI 1.04-1.27), celecoxib (HR 1.13; CI 1.01-1.26), diclofenac (HR 1.12; CI 1.04-1.20) or any NSAID use (HR 1.05; CI 1.02-1.09). No association was found for naproxen or ibuprofen. CONCLUSION: Ongoing treatment with NSAIDs...

  13. An examination of the thermodynamics of fusion, vaporization, and sublimation of ibuprofen and naproxen by correlation gas chromatography.

    Science.gov (United States)

    Maxwell, Rachel; Chickos, James

    2012-02-01

    The vaporization enthalpies of (S)-ibuprofen and (S)-naproxen measured by correlation gas chromatography at T = 298.15 K are reported and compared with literature values. Adjustment of the fusion enthalpies of (RS)- and (S)-ibuprofen and (S)-naproxen to T = 298.15 K and combined with the vaporization enthalpy of the (S)-enantiomer of both ibuprofen and naproxen also at T = 298.15 K resulted in the sublimation enthalpies of both (S)-enantiomers. On the assumption that the vaporization enthalpy of the racemic form of ibuprofen is within the experimental uncertainty of the chiral form, the sublimation enthalpy of racemic ibuprofen was also evaluated. The vaporization and sublimation enthalpies compare favorably to the most of the literature values for the racemic form of ibuprofen but differ from the value reported for chiral ibuprofen. The literature values of (S)-naproxen are somewhat smaller than the values measured in this work. The following vaporization enthalpies were measured for (S)-ibuprofen and (S)-naproxen, respectively: ΔH(vap) (298.15 K), 106.0 ± 5.5, 132.2 ± 5.0 kJ·mol(-1) . Sublimation enthalpies of 122.7 ± 5.6 and 155.2 ± 7.1 kJ·mol(-1) were calculated for the (S)-enantiomers of ibuprofen and naproxen and a value of 128.9 ± 5.8 kJ·mol(-1) was estimated for the racemic form of ibuprofen. Copyright © 2011 Wiley Periodicals, Inc.

  14. Ibuprofen arginate retains eNOS substrate activity and reverses endothelial dysfunction: implications for the COX-2/ADMA axis.

    Science.gov (United States)

    Kirkby, Nicholas S; Tesfai, Abel; Ahmetaj-Shala, Blerina; Gashaw, Hime H; Sampaio, Walkyria; Etelvino, Gisele; Leão, Nádia Miricéia; Santos, Robson A; Mitchell, Jane A

    2016-12-01

    Nonsteroidal antiinflammatory drugs, including ibuprofen, are among the most commonly used medications and produce their antiinflammatory effects by blocking cyclooxygenase (COX)-2. Their use is associated with increased risk of heart attacks caused by blocking COX-2 in the vasculature and/or kidney, with our recent work implicating the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), a cardiotoxic hormone whose effects can be prevented by l-arginine. The ibuprofen salt ibuprofen arginate (Spididol) was created to increase solubility but we suggest that it could also augment the NO pathway through codelivery of arginine. Here we investigated the idea that ibuprofen arginate can act to simultaneously inhibit COX-2 and preserve the NO pathway. Ibuprofen arginate functioned similarly to ibuprofen sodium for inhibition of mouse/human COX-2, but only ibuprofen arginate served as a substrate for NOS. Ibuprofen arginate but not ibuprofen sodium also reversed the inhibitory effects of ADMA and N G -nitro-l-arginine methyl ester on inducible NOS (macrophages) and endothelial NOS in vitro (aorta) and in vivo (blood pressure). These observations show that ibuprofen arginate provides, in one preparation, a COX-2 inhibitor and NOS substrate that could act to negate the harmful cardiovascular consequences mediated by blocking renal COX-2 and increased ADMA. While remarkably simple, our findings are potentially game-changing in the nonsteroidal antiinflammatory drug arena.-Kirkby, N. S., Tesfai, A., Ahmetaj-Shala, B., Gashaw, H. H., Sampaio, W., Etelvino, G., Leão, N. M., Santos, R. A., Mitchell, J. A. Ibuprofen arginate retains eNOS substrate activity and reverses endothelial dysfunction: implications for the COX-2/ADMA axis. © The Author(s).

  15. Compatibility of intravenous ibuprofen with lipids and parenteral nutrition, for use as a continuous infusion.

    Science.gov (United States)

    Garcia, Jowell; Garg, Alka; Song, Yunmei; Fotios, Ambados; Andersen, Chad; Garg, Sanjay

    2018-01-01

    There is increasing interest to administer ibuprofen as a continuous infusion instead of a traditional bolus for treating Patent Ductus Arteriosus (PDA). However, its compatibility data with commonly used drugs in the neonatal period, including parenteral nutrition (PN) and lipids is unavailable. The aim is to determine the compatibility of intravenous ibuprofen lysine with various ANZNN parenteral nutrition consensus group standard neonatal PN formulations and lipids. The PN and lipid solutions used in a tertiary neonatal unit were obtained. These included a Starter, Standard Preterm and low carbohydrate PN, and IV SMOF lipid admixture (SMOFLipid 20% 15 mL; Vitalipid N infant 4 mL, Soluvit N 1 mL) plus vitamin mixtures. 10% glucose was used as a control. 1:1 mixtures of different concentrations (1.25 to 5mg/mL) of ibuprofen lysine and each of the PN/glucose/lipid formulations were made. Samples were taken at hourly intervals for a total of 4 hours and tested for both physical (visual assessment, pH and microscopy) and chemical compatibility (High Performance Liquid Chromatography analysis). Zeta potential and particle diameter were measured for SMOF lipid admixture and ibuprofen combination to assess emulsion stability. 24 hour stability of ibuprofen dilution in 5 mL BD Luer-lok polypropylene syringes at 25°C was also assessed. Most PN formed opaque solutions when mixed with ibuprofen 2.5 and 5mg/mL solutions. However, ibuprofen dilution of 1.25mg/mL produced clear, colourless solutions with no microscopic particles when mixed with all PN/glucose/lipid formulations tested. Ibuprofen was chemically stable with all PN and SMOF lipid admixture, for a period of 4 hours. The zeta potential and particle diameter were within acceptable limits. Ibuprofen lysine was stable over 24 hours in Luer-lok polypropylene syringes. Ibuprofen 1.25mg/mL is physically and chemically compatible with 10% glucose, starter PN, standard preterm and low carbohydrate PN, and SMOF lipid

  16. Effects of constructed wetland design on ibuprofen removal – A mesocosm scale study

    DEFF Research Database (Denmark)

    Zhang, Liang; Lyu, Tao; Zhang, Yang

    2017-01-01

    This study aimed to investigate the effects of constructed wetland design (unsaturated, saturated and aerated saturated) and plant species (Juncus, Typha, Berula, Phragmites and Iris) on the mass removal and removal kinetics of the pharmaceutical ibuprofen. Planted systems had higher ibuprofen...

  17. Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma.

    Science.gov (United States)

    Sheehan, William J; Mauger, David T; Paul, Ian M; Moy, James N; Boehmer, Susan J; Szefler, Stanley J; Fitzpatrick, Anne M; Jackson, Daniel J; Bacharier, Leonard B; Cabana, Michael D; Covar, Ronina; Holguin, Fernando; Lemanske, Robert F; Martinez, Fernando D; Pongracic, Jacqueline A; Beigelman, Avraham; Baxi, Sachin N; Benson, Mindy; Blake, Kathryn; Chmiel, James F; Daines, Cori L; Daines, Michael O; Gaffin, Jonathan M; Gentile, Deborah A; Gower, W Adam; Israel, Elliot; Kumar, Harsha V; Lang, Jason E; Lazarus, Stephen C; Lima, John J; Ly, Ngoc; Marbin, Jyothi; Morgan, Wayne J; Myers, Ross E; Olin, J Tod; Peters, Stephen P; Raissy, Hengameh H; Robison, Rachel G; Ross, Kristie; Sorkness, Christine A; Thyne, Shannon M; Wechsler, Michael E; Phipatanakul, Wanda

    2016-08-18

    Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking. In a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids. Children in both groups received standardized asthma-controller therapies that were used in a simultaneous, factorially linked trial. Participants received a median of 5.5 doses (interquartile range, 1.0 to 15.0) of trial medication; there was no significant between-group difference in the median number of doses received (P=0.47). The number of asthma exacerbations did not differ significantly between the two groups, with a mean of 0.81 per participant with acetaminophen and 0.87 per participant with ibuprofen over 46 weeks of follow-up (relative rate of asthma exacerbations in the acetaminophen group vs. the ibuprofen group, 0.94; 95% confidence interval, 0.69 to 1.28; P=0.67). In the acetaminophen group, 49% of participants had at least one asthma exacerbation and 21% had at least two, as compared with 47% and 24%, respectively, in the ibuprofen group. Similarly, no significant differences were detected between acetaminophen and ibuprofen with respect to the percentage of asthma-control days (85.8% and 86.8%, respectively; P=0.50), use of an albuterol rescue inhaler (2.8 and 3.0 inhalations per week, respectively; P=0.69), unscheduled health care utilization for asthma (0.75 and 0.76 episodes per participant, respectively; P=0.94), or adverse events. Among

  18. Bioequivalence assessment of two formulations of ibuprofen

    KAUST Repository

    Al-Talla, Zeyad; Akrawi, Sabah H; Tolley, Luke T; Sioud, Salim H; Zaater, Mohammed F; Emwas, Abdul-Hamid M

    2011-01-01

    Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz , produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen , manufactured by Boots

  19. Acute cigarette smoke exposure causes lung injury in rabbits treated with ibuprofen

    Energy Technology Data Exchange (ETDEWEB)

    Witten, M.L.; Lemen, R.J.; Quan, S.F.; Sobonya, R.E.; Magarelli, J.L.; Bruck, D.C.

    1987-01-01

    We studied lung clearance of aerosolized technetium-labeled diethylenetriamine pentaacetic acid (/sup 99m/TcDTPA), plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2, and pulmonary edema as indices of lung injury in rabbits exposed to cigarette smoke (CSE). Forty-six rabbits were randomly assigned to 4 groups: control sham smoke exposure (SS, N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), and CSE ibuprofen-pretreated (CSE-I, N = 19). Ibuprofen (cyclooxygenase eicosanoid inhibitor) was administered as a single daily intramuscular injection (25 mg/kg) for 7 days before the experiment. Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 15-min counting period between each subset of breaths to determine /sup 99m/TcDTPA biological half-life (T1/2). In the ibuprofen pretreated group, CSE caused significant decreases in /sup 99m/TcDTPA T1/2 and dynamic lung compliance. Furthermore, these changes in lung function were accompanied by severe injury to type I alveolar cell epithelium, pulmonary edema, and frequently death of the rabbits. These findings suggest that inhibition of the cyclooxygenase pathway before CSE exacerbates lung injury in rabbits.

  20. Acute cigarette smoke exposure causes lung injury in rabbits treated with ibuprofen

    International Nuclear Information System (INIS)

    Witten, M.L.; Lemen, R.J.; Quan, S.F.; Sobonya, R.E.; Magarelli, J.L.; Bruck, D.C.

    1987-01-01

    We studied lung clearance of aerosolized technetium-labeled diethylenetriamine pentaacetic acid (/sup 99m/TcDTPA), plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2, and pulmonary edema as indices of lung injury in rabbits exposed to cigarette smoke (CSE). Forty-six rabbits were randomly assigned to 4 groups: control sham smoke exposure (SS, N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), and CSE ibuprofen-pretreated (CSE-I, N = 19). Ibuprofen (cyclooxygenase eicosanoid inhibitor) was administered as a single daily intramuscular injection (25 mg/kg) for 7 days before the experiment. Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 15-min counting period between each subset of breaths to determine /sup 99m/TcDTPA biological half-life (T1/2). In the ibuprofen pretreated group, CSE caused significant decreases in /sup 99m/TcDTPA T1/2 and dynamic lung compliance. Furthermore, these changes in lung function were accompanied by severe injury to type I alveolar cell epithelium, pulmonary edema, and frequently death of the rabbits. These findings suggest that inhibition of the cyclooxygenase pathway before CSE exacerbates lung injury in rabbits

  1. Effect of adding celecoxib to a single dose of gabapentin on postoperative pain relief

    Directory of Open Access Journals (Sweden)

    Mansour Choubsaz

    2015-01-01

    Full Text Available Background: In recent years, several studies with conflicting results have been done on the role of gabapentin and non-steroidal anti-inflammatory drugs in pre-emptive analgesia to control postoperative pain. The purpose of this study was to evaluate the effect of adding low doses of celecoxib to gabapentin on increasing the analgesic effect and patients’ satisfaction. Methods: In this double-blind randomized clinical trial, 130 patients with ASA I, II class were divided in two groups as they were the candidates for elective inguinal hernia surgery with spinal anesthesia. Before the surgery, the control group (G received 300 mg oral dose of gabapentin and the study group (GC received 100 mg celecoxib in addition to the above dose. Severity of patients’ pain was measured using the visual analogue scale (VAS. By the same token, the amount of painkillers usedwas measured and statistically analyzed. Results: The results suggested a statistically significant difference between the two groups in terms of pain level 4, 6 and 24 hours after surgery (P<0.05. Adding low-dose of celeoxib to gabapentin before the surgery and the combination of these two drugs caused further reduction of pain 4, 6 and 24 h after the surgery in comparison to the administration of gabapentin alone. Conclusion: Adding 100 mg celecoxib to 300 mg gabapentin resulted in a reduction of pain level 24 h after elective surgery of inguinal hernia in patients of control group (P<0.05. However, in terms of using painkillers (analgesics, there was no statistically significant difference between the two groups.

  2. Thermodynamic study of ibuprofen by adiabatic calorimetry and thermal analysis

    Energy Technology Data Exchange (ETDEWEB)

    Xu Fen; Sun Lixian; Tan Zhicheng; Liang Jianguo; Li Ruilian

    2004-03-23

    Molar heat capacities of ibuprofen were precisely measured with a small sample precision automated adiabatic calorimeter over the temperature range from 80 to 400 K. The polynomial functions of C{sub p,m} (J K{sup -1} mol{sup -1}) versus T were established on the heat capacity measurements by means of the least fitting square method. The functions are as follows: for solid ibuprofen, at the temperature range of 79.105 K{<=}T{<=}333.297 K, C{sub p,m}=144.27+77.046X+3.5171X{sup 2}+10.925X{sup 3}+11.224X{sup 4}, where X=(T-206.201)/127.096; for liquid ibuprofen, at the temperature range of 353.406 K{<=}T{<=}378.785 K, C{sub p,m}=325.79+8.9696X-1.6073X{sup 2}-1.5145X{sup 3}, where X=(T-366.095)/12.690. A fusion transition at T=348.02 K was found from the C{sub p}-T curve. The molar enthalpy and entropy of the fusion transition were determined to be 26.65 kJ mol{sup -1} and 76.58 J mol{sup -1} K{sup -1}, respectively. The thermodynamic functions on the base of the reference temperature of 298.15 K, (H{sub T}-H{sub 298.15}) and (S{sub T}-S{sub 298.15}), were derived. Thermal characteristic of ibuprofen was studied by thermo-gravimetric analysis (TG-DTG) and differential scanning calorimeter (DSC). The temperature of fusion, the molar enthalpy and entropy of fusion obtained by DSC were well consistent with those obtained by adiabatic calorimeter. The evaporation process of ibuprofen was investigated further by TG and DTG, and the activation energy of the evaporation process was determined to be 80.3{+-}1.4 kJ mol{sup -1}.

  3. Thermodynamic study of ibuprofen by adiabatic calorimetry and thermal analysis

    International Nuclear Information System (INIS)

    Xu Fen; Sun Lixian; Tan Zhicheng; Liang Jianguo; Li Ruilian

    2004-01-01

    Molar heat capacities of ibuprofen were precisely measured with a small sample precision automated adiabatic calorimeter over the temperature range from 80 to 400 K. The polynomial functions of C p,m (J K -1 mol -1 ) versus T were established on the heat capacity measurements by means of the least fitting square method. The functions are as follows: for solid ibuprofen, at the temperature range of 79.105 K≤T≤333.297 K, C p,m =144.27+77.046X+3.5171X 2 +10.925X 3 +11.224X 4 , where X=(T-206.201)/127.096; for liquid ibuprofen, at the temperature range of 353.406 K≤T≤378.785 K, C p,m =325.79+8.9696X-1.6073X 2 -1.5145X 3 , where X=(T-366.095)/12.690. A fusion transition at T=348.02 K was found from the C p -T curve. The molar enthalpy and entropy of the fusion transition were determined to be 26.65 kJ mol -1 and 76.58 J mol -1 K -1 , respectively. The thermodynamic functions on the base of the reference temperature of 298.15 K, (H T -H 298.15 ) and (S T -S 298.15 ), were derived. Thermal characteristic of ibuprofen was studied by thermo-gravimetric analysis (TG-DTG) and differential scanning calorimeter (DSC). The temperature of fusion, the molar enthalpy and entropy of fusion obtained by DSC were well consistent with those obtained by adiabatic calorimeter. The evaporation process of ibuprofen was investigated further by TG and DTG, and the activation energy of the evaporation process was determined to be 80.3±1.4 kJ mol -1

  4. New microbes as causative agents of Ibuprofen degradation capabilities in the hyporheic zone of a lowland stream

    Science.gov (United States)

    Njeru, Cyrus; Posselt, Malte; Horn, Marcus A.

    2017-04-01

    Ibuprofen is a non-steroidal anti-inflammatory pain reliever and among pharmaceutical residues detected in aquatic environments. Widespread use of the drug and incomplete removal during waste water treatment results in its persistence in effluents and receiving waters. Potential total removal by microbial activity in the hyporheic zone (HZ) of rivers downstream of wastewater treatment plant discharge sites has been hypothesized. Ibuprofen degradation associated microbial communities in are essentially unknown. To address this hypothesis, two sets of oxic HZ sediment microcosms spiked with ibuprofen only (5, 40, 200 and 400 µM), or ibuprofen and 1 mM acetate were set up under laboratory conditions. Ibuprofen degradation in non-sterile relative to autoclaved sediments indicated removal by microbial degradation. Ibuprofen was completely consumed in the absence and presence of supplemental acetate after approximately 11 and 16 days, respectively. Refeeding of ibuprofen and acetate after the first depletion resulted in complete degradation within 24 hours in all treatments. Metabolites of ibuprofen included 1-, 2-, 3-hydroxy- and carboxyibuprofen. Quantitative real-time PCR revealed no pronounced differences in copy numbers of 16S rRNA gene or transcripts between non-spiked controls and treatments. Time resolved triplicate amplicon Illumina MiSeq sequencing targeting the 16S rRNA genes and transcripts revealed increased relative abundances of Proteobacteria, Acidobacteria, Actinobacteria and Firmicutes in treatments with compared to those without ibuprofen. Alpha-, Beta- and Deltaproteobacteria were most active as indicated by RNA based analyses. Enrichment and isolation yielded new Alphaproteobacteria utilizing ibuprofen as sole carbon and energy source. The collective results indicated that (i) HZ sediments sustain efficient biotic (micro-)pollutant removal and (ii) are a reservoir of hitherto unknown microbial diversity associated with such ecosystem services

  5. ins-7 Gene expression is partially regulated by the DAF-16/IIS signaling pathway in Caenorhabditis elegans under celecoxib intervention.

    Directory of Open Access Journals (Sweden)

    Shanqing Zheng

    Full Text Available DAF-16 target genes are employed as reporters of the insulin/IGF-1 like signal pathway (IIS, and this is notably true when Caenorhabditis elegans (C. elegans is used to study the action of anti-aging compounds on IIS activity. However, some of these genes may not be specific to DAF-16, even if their expression levels are altered when DAF-16 is activated. Celecoxib was reported to extend the lifespan of C. elegans through activation of DAF-16. Our results confirmed the function of celecoxib on aging; however, we found that the expression of ins-7, a DAF-16 target gene, was abnormally regulated by celecoxib. ins-7 plays an important role in regulating aging, and its expression is suppressed in C. elegans when DAF-16 is activated. However, we found that celecoxib upregulated the expression of ins-7 in contrast to its role in DAF-16 activation. Our subsequent analysis indicated that the expression level of ins-7 in C. elegans was negatively regulated by DAF-16 activity. Additionally, its expression was also positively regulated by DAF-16-independent mechanisms, at least following external pharmacological intervention. Our study suggests that ins-7 is not a specific target gene of DAF-16, and should not be chosen as a reporter for IIS activity. This conclusion is important in the study of INSs on aging in C. elegans, especially under the circumstance of drug intervention.

  6. ins-7 Gene expression is partially regulated by the DAF-16/IIS signaling pathway in Caenorhabditis elegans under celecoxib intervention.

    Science.gov (United States)

    Zheng, Shanqing; Liao, Sentai; Zou, Yuxiao; Qu, Zhi; Liu, Fan

    2014-01-01

    DAF-16 target genes are employed as reporters of the insulin/IGF-1 like signal pathway (IIS), and this is notably true when Caenorhabditis elegans (C. elegans) is used to study the action of anti-aging compounds on IIS activity. However, some of these genes may not be specific to DAF-16, even if their expression levels are altered when DAF-16 is activated. Celecoxib was reported to extend the lifespan of C. elegans through activation of DAF-16. Our results confirmed the function of celecoxib on aging; however, we found that the expression of ins-7, a DAF-16 target gene, was abnormally regulated by celecoxib. ins-7 plays an important role in regulating aging, and its expression is suppressed in C. elegans when DAF-16 is activated. However, we found that celecoxib upregulated the expression of ins-7 in contrast to its role in DAF-16 activation. Our subsequent analysis indicated that the expression level of ins-7 in C. elegans was negatively regulated by DAF-16 activity. Additionally, its expression was also positively regulated by DAF-16-independent mechanisms, at least following external pharmacological intervention. Our study suggests that ins-7 is not a specific target gene of DAF-16, and should not be chosen as a reporter for IIS activity. This conclusion is important in the study of INSs on aging in C. elegans, especially under the circumstance of drug intervention.

  7. A comparative study of ibuprofen with paracetamol versus oxyphenbutazone with analgin combination in ophthalmic practice

    Directory of Open Access Journals (Sweden)

    Roy I

    1988-01-01

    Full Text Available A total of 200 patients of either sex with various ophthalmic inflammatory disorders of surgical and non-surgical types were treated with ibuprofen with paracetamol 1 tablet tid. or a combination of oxyphenbutazone and analgin-1 tablet t. i. d. for 7 days/ Patients in the ibuprofen with Paracetamol group recorded a signifi-cantly greater reduction in pain scores; on day 1 and 2 and in swelling scores on day 2, 5 and 7 as compared to patients receiving the combination of ox yphenbutazone and analgin. A significantly lesserr number of patients in the ibuprofen with paraeetamol group required escape analgesics. Seventy six per cent of patients in the Ibuprofen with paracetamol group were judged as showing a Very good - Good, response to treatment as against 55 per cent in the oxvphenbutazone-analgin group. It is concluded that ibuprofen with Paracetamol is superior in efficacy and a safer alternative to a combination of oxyphenbutazone and analgin.

  8. p53 is important for the anti-proliferative effect of ibuprofen in colon carcinoma cells

    International Nuclear Information System (INIS)

    Janssen, Astrid; Schiffmann, Susanne; Birod, Kerstin; Maier, Thorsten J.; Wobst, Ivonne; Geisslinger, Gerd; Groesch, Sabine

    2008-01-01

    S-ibuprofen which inhibits the cyclooxygenase-1/-2 and R-ibuprofen which shows no COX-inhibition at therapeutic concentrations have anti-carcinogenic effects in human colon cancer cells; however, the molecular mechanisms for these effects are still unknown. Using HCT-116 colon carcinoma cell lines, expressing either the wild-type form of p53 (HCT-116 p53 wt ) or being p(HCT-116 p53 -/- ), we demonstrated that both induction of a cell cycle block and apoptosis after S- and R-ibuprofen treatment is in part dependent on p53. Also in the in vivo nude mice model HCT-116 p53 -/- xenografts were less sensitive for S- and R-ibuprofen treatment than HCT-116 p53 wt cells. Furthermore, results indicate that induction of apoptosis in HCT-116 p53 wt cells after ibuprofen treatment is in part dependent on a signalling pathway including the neutrophin receptor p75 NTR , p53 and Bax

  9. Thermal and spectroscopic studies on solid ibuprofen complexes of lighter trivalent lanthanides

    Energy Technology Data Exchange (ETDEWEB)

    Gálico, D.A.; Holanda, B.B.C.; Guerra, R.B.; Legendre, A.O.; Rinaldo, D. [UNESP – Univ Estadual Paulista, Faculdade de Ciências, Departamento de Química, São Paulo CEP 17033-260 (Brazil); Treu-Filho, O. [UNESP – Univ Estadual Paulista, Instituto de Química, São Paulo CEP 14800-900 (Brazil); Bannach, G., E-mail: gilbert@fc.unesp.br [UNESP – Univ Estadual Paulista, Faculdade de Ciências, Departamento de Química, São Paulo CEP 17033-260 (Brazil)

    2014-01-10

    Highlights: • Lighter trivalent lanthanide complexes of ibuprofen have been synthesized. • The TG-FTIR allowed the identification of propane as the gas evolved during the thermal decomposition of the neodymium compound. • The thermal analysis provided information about the composition, dehydration, thermal behavior and thermal decomposition of the samples. • The theoretical and experimental spectroscopic studies suggest that the carboxylate group of ibuprofen is coordinated to the metals by a bidentate bond. - Abstract: Solid-state compounds of general formula Ln(L){sub 3}, in which L is ibuprofen and Ln stands for trivalent La, Ce, Pr, Nd, Sm and Eu, have been synthesized. Simultaneous thermogravimetry and differential thermal analysis (TG-DTA), X-ray powder diffractometry (DRX), complexometry, Fourier-transformed infrared spectroscopy (FTIR) and thermogravimetry coupled to Fourier-transformed infrared spectroscopy (TG-FTIR) were used to characterize these compounds. The results provided information concerning the chemical composition, dehydration, coordination modes of the ligands, crystallinity of the samples, thermal behavior and thermal decomposition of the compounds. The theoretical and experimental spectroscopic studies suggest that ibuprofen coordinates through the carboxylate group as a chelating ligand.

  10. Thermal and spectroscopic studies on solid ibuprofen complexes of lighter trivalent lanthanides

    International Nuclear Information System (INIS)

    Gálico, D.A.; Holanda, B.B.C.; Guerra, R.B.; Legendre, A.O.; Rinaldo, D.; Treu-Filho, O.; Bannach, G.

    2014-01-01

    Highlights: • Lighter trivalent lanthanide complexes of ibuprofen have been synthesized. • The TG-FTIR allowed the identification of propane as the gas evolved during the thermal decomposition of the neodymium compound. • The thermal analysis provided information about the composition, dehydration, thermal behavior and thermal decomposition of the samples. • The theoretical and experimental spectroscopic studies suggest that the carboxylate group of ibuprofen is coordinated to the metals by a bidentate bond. - Abstract: Solid-state compounds of general formula Ln(L) 3 , in which L is ibuprofen and Ln stands for trivalent La, Ce, Pr, Nd, Sm and Eu, have been synthesized. Simultaneous thermogravimetry and differential thermal analysis (TG-DTA), X-ray powder diffractometry (DRX), complexometry, Fourier-transformed infrared spectroscopy (FTIR) and thermogravimetry coupled to Fourier-transformed infrared spectroscopy (TG-FTIR) were used to characterize these compounds. The results provided information concerning the chemical composition, dehydration, coordination modes of the ligands, crystallinity of the samples, thermal behavior and thermal decomposition of the compounds. The theoretical and experimental spectroscopic studies suggest that ibuprofen coordinates through the carboxylate group as a chelating ligand

  11. Ibuprofen Versus Fennel for the Relief of Postpartum Pain: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Parvin Asti

    2011-06-01

    Full Text Available Objective: The present study aimed to compare the value of ibuprofen and fennel for postpartum painrelief in women with normal vaginal delivery.Materials and methods:In this randomized clinical trial we studied 90 women referring to obstetricsward for Normal Vaginal Delivery (NVD in Assali hospital in Khoramabad. Women were randomlyallocated to receive either oral ibuprofen or oral fennel by stratified random sampling technique. Allwomen were asked to give pain score by visual analogue scale before and at 1, 2, 3 and 4 hours aftertreatment.Results: Difference between fennel and ibuprofen groups was not significant considering severity of painbefore (P=0.22. Difference between two groups considering mean severity of pain one hour aftertreatment (P=0.57 was not significant. But comparing the mean of pain severity in two groups, showedsignificant difference after two (p<0.023, three (p<0.001 and four (p<0.001 hours after treatment.Conclusion: Ibuprofen and fennel were effective for relief of postpartum pain without any notable sideeffects, but in general ibuprofen was more effective than fennel. More studies are needed to confirm theefficacy of fennel in pain relief especially in postpartum women which must be compared to a notreatment control group.

  12. Synergistic effects of celecoxib and bupropion in a model of chronic inflammation-related depression in mice.

    Directory of Open Access Journals (Sweden)

    Izaque S Maciel

    Full Text Available This study was aimed to characterize the depression-like behaviour in the classical model of chronic inflammation induced by Complete Freund's Adjuvant (CFA. Male Swiss mice received an intraplantar (i.pl. injection of CFA (50 µl/paw or vehicle. Behavioural and inflammatory responses were measured at different time-points (1 to 4 weeks, and different pharmacological tools were tested. The brain levels of IL-1β and BDNF, or COX-2 expression were also determined. CFA elicited a time-dependent edema formation and mechanical allodynia, which was accompanied by a significant increase in the immobility time in the tail suspension (TST or forced-swimming (FST depression tests. Repeated administration of the antidepressants imipramine (10 mg/kg, fluoxetine (20 mg/kg and bupropion (30 mg/kg significantly reversed depression-like behaviour induced by CFA. Predictably, the anti-inflammatory drugs dexamethasone (0.5 mg/kg, indomethacin (10 mg/kg and celecoxib (30 mg/kg markedly reduced CFA-induced edema. The oral treatment with the analgesic drugs dipyrone (30 and 300 mg/kg or pregabalin (30 mg/kg significantly reversed the mechanical allodyinia induced by CFA. Otherwise, either dipyrone or pregabalin (both 30 mg/kg did not significantly affect the paw edema or the depressive-like behaviour induced by CFA, whereas the oral treatment with dipyrone (300 mg/kg was able to reduce the immobility time in TST. Noteworthy, CFA-induced edema was reduced by bupropion (30 mg/kg, and depression behaviour was prevented by celecoxib (30 mg/kg. The co-treatment with bupropion and celecoxib (3 mg/kg each significantly inhibited both inflammation and depression elicited by CFA. The same combined treatment reduced the brain levels of IL-1β, as well as COX-2 immunopositivity, whilst it failed to affect the reduction of BDNF levels. We provide novel evidence on the relationship between chronic inflammation and depression, suggesting that combination of antidepressant and

  13. Potential of Essential Oils as Penetration Enhancers for Transdermal Administration of Ibuprofen to Treat Dysmenorrhoea

    Directory of Open Access Journals (Sweden)

    Jun Chen

    2015-10-01

    Full Text Available The present study was conducted to evaluate and compare five essential oils (EOs as penetration enhancers (PEs to improve the transdermal drug delivery (TDD of ibuprofen to treat dysmenorrhoea. The EOs were prepared using the steam distillation method and their chemical compositions were identified by GC-MS. The corresponding cytotoxicities were evaluated in epidermal keartinocyte HaCaT cell lines by an MTT assay. Furthermore, the percutaneous permeation studies were carried out to compare the permeation enhancement effect of EOs. Then the therapeutic efficacy of ibuprofen with EOs was evaluated using dysmenorrheal model mice. The data supports a decreasing trend of skin cell viability in which Clove oil >Angelica oil > Chuanxiong oil > Cyperus oil > Cinnamon oil >> Azone. Chuanxiong oil and Angelica oil had been proved to possess a significant permeation enhancement for TDD of ibuprofen. More importantly, the pain inhibitory intensity of ibuprofen hydrogel was demonstrated to be greater with Chuanxiong oil when compared to ibuprofen without EOs (p < 0.05. The contents of calcium ion and nitric oxide (NO were also significantly changed after the addition of Chuanxiong oil (p < 0.05. In summary, we suggest that Chuanxiong oil should be viewed as the best PE for TDD of ibuprofen to treat dysmenorrhea.

  14. Association of Prenatal Ibuprofen Exposure with Birth Weight and Gestational Age: A Population-Based Sibling Study.

    Science.gov (United States)

    Nezvalová-Henriksen, Kateřina; Wood, Mollie; Spigset, Olav; Nordeng, Hedvig

    2016-01-01

    Three studies so far have investigated the effect of prenatal non-steroidal anti-inflammatory drug (NSAID) exposure on birth weight and gestational age. The aim in this study was to evaluate the association of prenatal ibuprofen with birth weight and gestational age at birth, using a sibling design in an attempt to adjust for the possibility of familial confounding. Using data from the Norwegian Mother and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN), we identified 28 597 siblings, of whom 1080 were prenatally exposed to ibuprofen and 26 824 were not exposed to any NSAID. Random and fixed effects models with propensity score adjustment were used to evaluate the effects of ibuprofen exposure on birth weight and gestational age. Ibuprofen exposure during the first trimester was associated with a decrease in birth weight of 79 grams (95% confidence interval -133 to -25 grams). In contrast, second and/or third trimester exposure, and duration of exposure had no impact on the effect estimates. We found no association between ibuprofen exposure and gestational age at birth. Our results suggest that prenatal exposure to ibuprofen during the first trimester is associated with a slight decrease in birth weight. The association does not seem to be attributable to shared genetics and family environment, and could be explained by either exposure to ibuprofen, or to non-shared confounding between pregnancies.

  15. Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations

    Science.gov (United States)

    Bonelli, Patrizia; Tuccillo, Franca M; Federico, Antonella; Napolitano, Maria; Borrelli, Antonella; Melisi, Daniela; Rimoli, Maria G; Palaia, Raffaele; Arra, Claudio; Carinci, Francesco

    2012-01-01

    Purpose Epidemiological, clinical, and laboratory studies have suggested that ibuprofen, a commonly used nonsteroidal anti-inflammatory drug, inhibits the promotion and proliferation of certain tumors. Recently, we demonstrated the antiproliferative effects of ibuprofen on the human gastric cancer cell line MKN-45. However, high doses of ibuprofen were required to elicit these antiproliferative effects in vitro. The present research compared the antiproliferative effects of ibuprofen delivered freely and released by poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in MKN-45 cells. Methods MKN-45 human gastric adenocarcinoma cells were treated with ibuprofen-loaded PLGA NPs. The proliferation of MKN-45 cells was then assessed by cell counting. The uptake of NPs was imaged by fluorescence microscopy and flow cytometry. The release of ibuprofen from ibuprofen-loaded PLGA NPs in the cells was evaluated by gas chromatography–mass spectrometry. Results Dramatic inhibition of cellular proliferation was observed in cells treated with ibuprofen-loaded PLGA NPs versus those treated with free ibuprofen at the same concentration. The localization of NPs was cytoplasmic. The initiation of ibuprofen release was rapid, commencing within 2 hours, and then increased slowly over time, reaching a maximum concentration at 24 hours. The inhibition of proliferation was confirmed to be due to the intracellular release of ibuprofen from the NPs. Using PLGA NPs as carriers, ibuprofen exerted an antiproliferative activity at concentrations > 100 times less than free ibuprofen, suggesting greater efficiency and less cellular toxicity. In addition, when carried by PLGA NPs, ibuprofen more quickly induced the expression of transcripts involved in proliferation and invasiveness processes. Conclusion Ibuprofen exerted an antiproliferative effect on MKN-45 cells at low concentrations. This effect was achieved using PLGA NPs as carriers of low doses of ibuprofen. PMID:23180963

  16. Timing of ibuprofen use and musculoskeletal adaptations to exercise training in older adults

    Directory of Open Access Journals (Sweden)

    Catherine M. Jankowski

    2015-01-01

    The difference between groups in the change in BMD was not significant when IP was compared with either PP (hip, −0.5% (−1.4, 0.4; spine, 0.1% (−0.9, 1.2 or PI (hip, 0.3% (−0.6, 1.2; spine, 0.5% (−0.5, 1.5. Ibuprofen use appeared to have more adverse effects on BMD in women than men. The study demonstrated that ibuprofen use did not significantly alter the BMD adaptations to exercise in older adults, but this finding should be interpreted cautiously. It had been expected that the inhibition of bone formation by ibuprofen would be more robust in men than in women, but this did not appear to be the case and may have limited the power to detect the effects of ibuprofen. Further research is needed to understand whether NSAID use counteracts, in part, the beneficial effects of exercise on bone.

  17. Design, Synthesis, and Characterization of Novel Thiol-Derivatized Ibuprofen Monolayer Protected Gold Clusters

    International Nuclear Information System (INIS)

    Lee, K.H.; Lee, K.H.; Lin, Y.Sh.; Huang, P.J.

    2013-01-01

    A series of new thiol-derivatized ibuprofen monolayer protected gold clusters have been prepared by amidation of ibuprofen with alkyl alcohol or aminophenol affording the carboxamide, N-hydroxyalkyl amide 2, and N-hydroxyphenyl amide 6, which were then tosylate with p-toluenesulfonyl chloride at hydroxyl group to give 3 and 7. Reactions of 3 and 7 with NaSH afforded the mercapto derivatives 4 and 8. Conducting Brust’s reaction with a 3:1 mole ratio of thiolate ibuprofen/ AuCl 4 - yielded polydisperse thiol-derivatized ibuprofen-MPCs 5 and 9. All compounds have been identified by NMR, MS, UV, and IR spectroscopies. Compounds 4 and 8 and the MPCs 5 and 9 have been investigated by using the method of 1 H NMR spectroscopy. The broadening of the signals from 0.8 to 2.0 ppm in 1 H NMR spectrum of MPCs 5 and 9 confirmed the success of the conjugation of thiol-containing derivatives with nano gold cluster.

  18. The Use of Ibuprofen in Posttonsillectomy Analgesia and Its Effect on Posttonsillectomy Hemorrhage Rate.

    Science.gov (United States)

    Pfaff, Julia A; Hsu, Kevin; Chennupati, Sri Kiran

    2016-09-01

    To determine the effect of ibuprofen on posttonsillectomy bleeding when compared with codeine in posttonsillectomy analgesia. Case series with chart review. Tertiary care children's hospital, Philadelphia, Pennsylvania. On July 1, 2012, our institution transitioned from acetaminophen with codeine to ibuprofen for posttonsillectomy analgesia. Pediatric patients (0-18 years old) who underwent surgery from July 1, 2010, to June 30, 2012, were placed in the codeine cohort, and those who underwent surgery from July 1, 2012, to June 30, 2014, were placed in the ibuprofen cohort. A total of 6014 patients underwent tonsillectomy between July 1, 2010, and June 30, 2014, and 211 patients presented for posttonsillectomy hemorrhage during the same period. The incidence of readmission for posttonsillectomy hemorrhage was 3.4% and 3.6% (P = .63; odds ratio [OR] = 1.07; 95% confidence interval [95% CI]: 0.811-1.410) for the codeine and ibuprofen groups, respectively, and the incidence of second operation for control of posttonsillectomy bleeding for the codeine and ibuprofen groups was 1.9% and 2.2% (P = .54; OR = 1.117; 95% CI: 0.781-1.600), respectively. Patients aged 11 to 18 years demonstrated a higher incidence of posttonsillectomy bleeding events overall. When age is controlled, multivariate logistic regression demonstrated no statistically significant increase in posttonsillectomy bleeding events among pediatric patients treated with ibuprofen versus patients treated with codeine (readmission: P = .617; OR = 0.932; 95% CI: 0.707-1.228; reoperation: P = .513; OR = 0.887; 95% CI: 0.618-1.272). Age is an independent risk factor for posttonsillectomy bleeding. When age is controlled, there is no statistically significant increase in the incidence of posttonsillectomy bleeding events among patients treated with ibuprofen when compared to patients treated with codeine. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  19. Ibuprofen 400 mg is effective in women, and women are well represented in trials

    Directory of Open Access Journals (Sweden)

    Moore R Andrew

    2002-11-01

    Full Text Available Abstract Background A recent article in the New Scientist argued that women were under-represented in clinical trials which, until now, had masked the finding that ibuprofen 400 mg was ineffective in women. Methods Meta-analysis of randomised, double-blind placebo-controlled trials of ibuprofen 400 mg in acute pain, and use of individual patient information were planned to test the hypothesis that ibuprofen is ineffective in women. For each trial the proportion of women participating, the number of patients with at least 50% pain relief and the overall event rate for ibuprofen 400 mg and placebo was calculated. For each patient percentage pain relief was calculated, and the numbers of women and men achieving at least 50% pain relief used to calculate number-needed-to-treat (NNT for ibuprofen 400 mg compared to placebo. Results Thirty-seven included trials had 3,577 patients, 67% of whom were women. The proportion with at least 50% pain relief was unaffected by how many women were included. In an analysis of 678 individual patients the proportion of women and men with at least 50% pain relief was the same, NNT 3.4 (2.6 to 4.6 and 2.5 (2.0 to 3.3 respectively. Conclusion There is no clinically meaningful difference in the efficacy of ibuprofen 400 mg between men and women experiencing moderate to severe postoperative pain and women were well represented.

  20. COX-2 inhibition improves immunotherapy and is associated with decreased numbers of myeloid-derived suppressor cells in mesothelioma. Celecoxib influences MDSC function

    International Nuclear Information System (INIS)

    Veltman, Joris D; Lambers, Margaretha EH; Nimwegen, Menno van; Hendriks, Rudi W; Hoogsteden, Henk C; Aerts, Joachim GJV; Hegmans, Joost PJJ

    2010-01-01

    Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature cells that accumulates in tumour-bearing hosts. These cells are induced by tumour-derived factors (e.g. prostaglandins) and have a critical role in immune suppression. MDSC suppress T and NK cell function via increased expression of arginase I and production of reactive oxygen species (ROS) and nitric oxide (NO). Immune suppression by MDSC was found to be one of the main factors for immunotherapy insufficiency. Here we investigate if the in vivo immunoregulatory function of MDSC can be reversed by inhibiting prostaglandin synthesis by specific COX-2 inhibition focussing on ROS production by MDSC subtypes. In addition, we determined if dietary celecoxib treatment leads to refinement of immunotherapeutic strategies. MDSC numbers and function were analysed during tumour progression in a murine model for mesothelioma. Mice were inoculated with mesothelioma tumour cells and treated with cyclooxygenase-2 (COX-2) inhibitor celecoxib, either as single agent or in combination with dendritic cell-based immunotherapy. We found that large numbers of infiltrating MDSC co-localise with COX-2 expression in those areas where tumour growth takes place. Celecoxib reduced prostaglandin E2 levels in vitro and in vivo. Treatment of tumour-bearing mice with dietary celecoxib prevented the local and systemic expansion of all MDSC subtypes. The function of MDSC was impaired as was noticed by reduced levels of ROS and NO and reversal of T cell tolerance; resulting in refinement of immunotherapy. We conclude that celecoxib is a powerful tool to improve dendritic cell-based immunotherapy and is associated with a reduction in the numbers and suppressive function of MDSC. These data suggest that immunotherapy approaches benefit from simultaneously blocking cyclooxygenase-2 activity

  1. Enhanced longevity by ibuprofen, conserved in multiple species, occurs in yeast through inhibition of tryptophan import.

    Directory of Open Access Journals (Sweden)

    Chong He

    2014-12-01

    Full Text Available The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies. However, a general pro-longevity role for ibuprofen and its mechanistic basis remains unclear. Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster, indicative of conserved eukaryotic longevity effects. Studies in yeast indicate that ibuprofen destabilizes the Tat2p permease and inhibits tryptophan uptake. Loss of Tat2p increased replicative lifespan (RLS, but ibuprofen did not increase RLS when Tat2p was stabilized or in an already long-lived strain background impaired for aromatic amino acid uptake. Concomitant with lifespan extension, ibuprofen moderately reduced cell size at birth, leading to a delay in the G1 phase of the cell cycle. Similar changes in cell cycle progression were evident in a large dataset of replicatively long-lived yeast deletion strains. These results point to fundamental cell cycle signatures linked with longevity, implicate aromatic amino acid import in aging and identify a largely safe drug that extends lifespan across different kingdoms of life.

  2. Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of Tryptophan Import

    Science.gov (United States)

    He, Chong; Tsuchiyama, Scott K.; Nguyen, Quynh T.; Plyusnina, Ekaterina N.; Terrill, Samuel R.; Sahibzada, Sarah; Patel, Bhumil; Faulkner, Alena R.; Shaposhnikov, Mikhail V.; Tian, Ruilin; Tsuchiya, Mitsuhiro; Kaeberlein, Matt; Moskalev, Alexey A.; Kennedy, Brian K.; Polymenis, Michael

    2014-01-01

    The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies. However, a general pro-longevity role for ibuprofen and its mechanistic basis remains unclear. Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster, indicative of conserved eukaryotic longevity effects. Studies in yeast indicate that ibuprofen destabilizes the Tat2p permease and inhibits tryptophan uptake. Loss of Tat2p increased replicative lifespan (RLS), but ibuprofen did not increase RLS when Tat2p was stabilized or in an already long-lived strain background impaired for aromatic amino acid uptake. Concomitant with lifespan extension, ibuprofen moderately reduced cell size at birth, leading to a delay in the G1 phase of the cell cycle. Similar changes in cell cycle progression were evident in a large dataset of replicatively long-lived yeast deletion strains. These results point to fundamental cell cycle signatures linked with longevity, implicate aromatic amino acid import in aging and identify a largely safe drug that extends lifespan across different kingdoms of life. PMID:25521617

  3. Ibuprofen-in-cyclodextrin-in-W/O/W emulsion - Improving the initial and long-term encapsulation efficiency of a model active ingredient.

    Science.gov (United States)

    Hattrem, Magnus N; Kristiansen, Kåre A; Aachmann, Finn L; Dille, Morten J; Draget, Kurt I

    2015-06-20

    A challenge in formulating water-in-oil-in-water (W/O/W) emulsions is the uncontrolled release of the encapsulated compound prior to application. Pharmaceuticals and nutraceuticals usually have amphipathic nature, which may contribute to leakage of the active ingredient. In the present study, cyclodextrins (CyDs) were used to impart a change in the relative polarity and size of a model compound (ibuprofen) by the formation of inclusion complexes. Various inclusion complexes (2-hydroxypropyl (HP)-β-CyD-, α-CyD- and γ-CyD-ibuprofen) were prepared and presented within W/O/W emulsions, and the initial and long-term encapsulation efficiency was investigated. HP-β-CyD-ibuprofen provided the highest encapsulation of ibuprofen in comparison to a W/O/W emulsion with unassociated ibuprofen confined within the inner water phase, with a four-fold increase in the encapsulation efficiency. An improved, although lower, encapsulation efficiency was obtained for the inclusion complex γ-CyD-ibuprofen in comparison to HP-β-CyD-ibuprofen, whereas α-CyD-ibuprofen had a similar encapsulation efficiency to that of unassociated ibuprofen. The lower encapsulation efficiency of ibuprofen in combination with α-CyD and γ-CyD was attributed to a lower association constant for the γ-CyD-ibuprofen inclusion complex and the ability of α-CyD to form inclusion complexes with fatty acids. For the W/O/W emulsion prepared with HP-β-CyD-ibuprofen, the highest encapsulation of ibuprofen was obtained at hyper- and iso-osmotic conditions and by using an excess molar ratio of CyD to ibuprofen. In the last part of the study, it was suggested that the chemical modification of the HP-β-CyD molecule did not influence the encapsulation of ibuprofen, as a similar encapsulation efficiency was obtained for an inclusion complex prepared with mono-1-glucose-β-CyD. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Ibuprofen - a Safe Analgesic During Cardiac Surgery Recovery? A Randomized Controlled Trial?

    Directory of Open Access Journals (Sweden)

    Saddiq Mohammad Qazi

    2015-12-01

    Conclusion: The results of this study suggest that patients treated postoperatively, following cardiac surgery, are at no greater risk of harm if short term slow release ibuprofen combined with lansoprazole treatment is used when compared to an oxycodone based regimen. Renal function should, however, be closely monitored and in the event of any decrease in renal function ibuprofen must be discontinued.

  5. A prospective phase I-II trial of the cyclooxygenase-2 inhibitor celecoxib in patients with carcinoma of the cervix with biomarker assessment of the tumor microenvironment

    International Nuclear Information System (INIS)

    Herrera, Fernanda G.; Chan, Philip; Doll, Corinne; Milosevic, Michael; Oza, Amit; Syed, Amy; Pintilie, Melania; Levin, Wilfred; Manchul, Lee; Fyles, Anthony

    2007-01-01

    Purpose: To evaluate the toxicity and effectiveness of celecoxib in combination with definitive chemoradiotherapy (CRT) in women with locally advanced cervical cancer. Methods and Materials: Thirty-one patients were accrued to a phase I-II trial of celecoxib 400 mg by mouth twice per day for 2 weeks before and during CRT. Tumor oxygenation (HP 5 ) and interstitial fluid pressure (IFP) were measured before and 2 weeks after celecoxib administration alone. The median follow-up time was 2.7 years (range, 1.1-4.4 years). Results: The most common acute G3/4 toxicities were hematologic (4/31, 12.9%) and gastrointestinal (5/31, 16.1%) largely attributed to chemotherapy. Late G3/4 toxicity was seen in 4 of 31 patients (13.7% actuarial risk at 2 yr), including fistulas in 3 patients (9.7%). Within the first year of follow-up, 25 of 31 patients (81%) achieved complete response (CR), of whom 20 remained in CR at last follow-up. After 2 weeks of celecoxib administration before CRT, the median IFP decreased slightly (median absolute, -4.6 mm Hg; p = 0.09; relative, -21%; p = 0.07), whereas HP 5 did not change significantly (absolute increase, 3.6%; p = 0.51; median relative increase, 11%; p = 0.27). No significant associations were seen between changes in HP 5 or IFP and response to treatment (p = 0.2, relative HP 5 change and p = 0.14, relative IFP change). Conclusions: Celecoxib in combination with definitive CRT is associated with acceptable acute toxicity, but higher than expected late complications. Celecoxib is associated with a modest reduction in the angiogenic biomarker IFP, but this does not correspond with tumor response

  6. Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Desdoits-Lethimonier, Christèle; Mackey, Abigail L

    2018-01-01

    Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects...... with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig...... and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby...

  7. A Randomized Placebo Controlled Trial of Ibuprofen for Respiratory Syncytial Virus Infection in a Bovine Model.

    Directory of Open Access Journals (Sweden)

    Paul Walsh

    Full Text Available Respiratory syncytial virus (RSV is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to the virus. RSV is accompanied by elevated prostaglandin E2 (PGE2 which is followed by neutrophil led inflammation in the lung. Ibuprofen is a prototypical non-steroidal anti-inflammatory drug that decreases PGE2 levels by inhibiting cyclooxygenase.We hypothesized that treatment of RSV with ibuprofen would decrease PGE2 levels, modulate the immune response, decrease clinical illness, and decrease the histopathological lung changes in a bovine model of RSV. We further hypothesized that viral replication would be unaffected.We performed a randomized placebo controlled trial of ibuprofen in 16 outbred Holstein calves that we infected with RSV. We measured clinical scores, cyclooxygenase, lipoxygenase and endocannabinoid products in plasma and mediastinal lymph nodes and interleukin (Il-4, Il-13, Il-17 and interferon-γ in mediastinal lymph nodes. RSV shedding was measured daily and nasal Il-6, Il-8 and Il-17 every other day. The calves were necropsied on Day 10 post inoculation and histology performed.One calf in the ibuprofen group required euthanasia on Day 8 of infection for respiratory distress. Clinical scores (p<0.01 and weight gain (p = 0.08 seemed better in the ibuprofen group. Ibuprofen decreased cyclooxygenase, lipoxygenase, and cytochrome P450 products, and increased monoacylglycerols in lung lymph nodes. Ibuprofen modulated the immune response as measured by narrowed range of observed Il-13, Il-17 and IFN-γ gene expression in mediastinal lymph nodes. Lung histology was not different between groups, and viral shedding was increased in calves randomized to ibuprofen.Ibuprofen decreased PGE2, modulated the immune response, and improved clinical outcomes

  8. Cocrystal Screening of Ibuprofen with Oxalic Acid and Citric Acid via Grinding Method

    Science.gov (United States)

    Othman, M. F.; Anuar, N.; Rahman, S. Ad; Taifuddin, N. A. Ahmad

    2018-05-01

    Ibuprofen is a Class II Biological Safety Class (BSC) drugs used for relief of arthritis, as an analgesic and possesses the effect of antiplatelet. The major problem involves in ibuprofen is it has a low solubility and high permeability thus causes an unsatisfactory therapeutic effect to humans. Thus, in this work, alteration of ibuprofen’s physicochemical properties is conducted by means of cocrystallization technique. Co-crystallizations of ibuprofen were prepared with selected coformers using dry grinding and liquid assisted grinding (LAG) techniques in different molar ratios while ethanol and propanol were used as a solvent. The new crystalline forms were identified and characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and fourier transform infrared spectroscopy (FTIR). Analysis for Ibuprofen-Citric acid (IBP-CA) system, co-crystal was successfully formed in 1:2, 1:3, 2:1 and 3:1 molar ratios for neat grinding method although the co-crystal produced is unstable. Meanwhile, for Ibuprofen-Oxalic acid (IBP-OA) system, the co-crystal formation was identified only in 1:1, 1:2 and 1:3 molar ratios for the neat grinding method. LAG method shows that co-crystal formation was unsuccessful in both solvents for IBP-CA, while IBP-OA co-crystal was formed in the molar ratio 1:1, 2:1 and 3:1 in ethanol, and 2:1 and 3:1 in propanol.

  9. Ibuprofen-conjugated hyaluronate/polygalacturonic acid hydrogel for the prevention of epidural fibrosis.

    Science.gov (United States)

    Lin, Cheng-Yi; Peng, Hsiu-Hui; Chen, Mei-Hsiu; Sun, Jui-Sheng; Chang, Chih-Ju; Liu, Tse-Ying; Chen, Ming-Hong

    2016-05-01

    The formation of fibrous tissue is part of the natural healing response following a laminectomy. Severe scar tissue adhesion, known as epidural fibrosis, is a common cause of failed back surgery syndrome. In this study, by combining the advantages of drug treatment with a physical barrier, an ibuprofen-conjugated crosslinkable polygalacturonic acid and hyaluronic acid hydrogel was developed for epidural fibrosis prevention. Conjugation was confirmed and measured by 1D(1)H NMR spectroscopy.In vitroanalysis showed that the ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel showed low cytotoxicity. In addition, the conjugated ibuprofen decreased prostaglandin E2production of the lipopolysaccharide-induced RAW264.7 cells. Histological data inin vivostudies indicated that the scar tissue adhesion of laminectomized male adult rats was reduced by the application of our ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel. Its use also reduced the population of giant cells and collagen deposition of scar tissue without inducing extensive cell recruitment. The results of this study therefore suggest that the local delivery of ibuprofenviaa polygalacturonic acid-hyaluronic acid-based hydrogel reduces the possibility of epidural fibrosis. © The Author(s) 2016.

  10. Association Between Ibuprofen Use and Severity of Surgically Managed Posttonsillectomy Hemorrhage.

    Science.gov (United States)

    Mudd, Pamela A; Thottathil, Princy; Giordano, Terri; Wetmore, Ralph F; Elden, Lisa; Jawad, Abbas F; Ahumada, Luis; Gálvez, Jorge A

    2017-07-01

    Ibuprofen used in postoperative management of pain after tonsillectomy has not been shown to increase the overall risk for posttonsillectomy hemorrhage (PTH). The severity of bleeding is difficult to quantify but may be a more important outcome to measure. To evaluate the association between ibuprofen use and severity of PTH using transfusion events as a marker of severity. This retrospective cohort study identified 8868 patients who underwent tonsillectomy from January 20, 2011, through June 30, 2014, at the tertiary academic Children's Hospital of Philadelphia. Of these patients, 6710 met the inclusion criteria. Data were collected using electronic database acquisition and query. Multivariate analysis was performed to identify independent prognostic factors for PTH and receipt of transfusion. Of the 6710 patients who met criteria for analysis (3454 male [51.5%] and 3256 female [48.5%]; median age, 5.4 years [interquartile range, 3.7-8.2 years]), 222 (3.3%) presented with PTH that required surgical control (sPTH). A total of 15 of the 8868 patients required transfusion for an overall risk for transfusion after tonsillectomy of 0.2%. Fifteen of 222 patients undergoing sPTH (6.8%) received transfusions. No significant independent increased risk for sPTH was associated with use of ibuprofen (adjusted odds ratio [OR], 0.90; 95% CI, 0.68-1.19). A significant independent association was found in the risk for sPTH in patients 12 years or older (adjusted OR, 2.74; 95% CI, 1.99-3.76) and in patients with a history of recurrent tonsillitis (adjusted OR, 1.52; 95% CI, 1.12-2.06). When using transfusion rates as a surrogate for severity of sPTH, transfusion increased by more than 3-fold among ibuprofen users compared with nonusers (adjusted OR, 3.16; 95% CI, 1.01-9.91), and the upper limit of the 95% CI suggests the difference could be nearly 10 times greater. The risk for sPTH is not increased with use of postoperative ibuprofen but is increased in patients 12 years or older

  11. Critical solvent properties affecting the particle formation process and characteristics of celecoxib-loaded plga microparticles via spray-drying.

    Science.gov (United States)

    Wan, Feng; Bohr, Adam; Maltesen, Morten Jonas; Bjerregaard, Simon; Foged, Camilla; Rantanen, Jukka; Yang, Mingshi

    2013-04-01

    It is imperative to understand the particle formation mechanisms when designing advanced nano/microparticulate drug delivery systems. We investigated how the solvent power and volatility influence the texture and surface chemistry of celecoxib-loaded poly (lactic-co-glycolic acid) (PLGA) microparticles prepared by spray-drying. Binary mixtures of acetone and methanol at different molar ratios were applied to dissolve celecoxib and PLGA prior to spray-drying. The resulting microparticles were characterized with respect to morphology, texture, surface chemistry, solid state properties and drug release profile. The evaporation profiles of the feed solutions were investigated using thermogravimetric analysis (TGA). Spherical PLGA microparticles were obtained, irrespectively of the solvent composition. The particle size and surface chemistry were highly dependent on the solvent power of the feed solution. An obvious burst release was observed for the microparticles prepared by the feed solutions with the highest amount of poor solvent for PLGA. TGA analysis revealed distinct drying kinetics for the binary mixtures. The particle formation process is mainly governed by the PLGA precipitation rate, which is solvent-dependent, and the migration rate of celecoxib molecules during drying. The texture and surface chemistry of the spray-dried PLGA microparticles can therefore be tailored by adjusting the solvent composition.

  12. Phase II trial of Uracil/Tegafur plus leucovorin and celecoxib combined with radiotherapy in locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Morak, Marjolein J.M.; Richel, Dick J.; Eijck, Casper H.J. van; Nuyttens, Joost J.M.E.; Gaast, Ate van der; Vervenne, Walter L.; Padmos, Esther E.; Schaake, Eva E.; Busch, Olivier R.C.; Tienhoven, Geertjan van

    2011-01-01

    Background and purpose: To investigate the efficacy and toxicity of a short intensive Uracil/Tegafur (UFT) based chemoradiotherapy scheme combined with celecoxib in locally advanced pancreatic cancer. Material and methods: The Academic Medical Centre, Amsterdam and the Erasmus Medical Centre, Rotterdam enrolled 83 eligible patients with unresectable pancreatic cancer in a prospective multicentre phase II study. Median age was 62 years, median tumour size 40 mm and the majority of the patients (85%) had pancreatic head cancers. Treatment consisted of 20 x 2.5 Gy radiotherapy combined with UFT 300 mg/m 2 per day, leucovorin (folinic acid) 30 mg and celecoxib 800 mg for 28 days concomitant with radiotherapy. Four patients were lost to follow-up. Results: Full treatment compliance was achieved in 55% of patients, 80% received at least 3 weeks of treatment. No partial or complete response was observed. Median survival was 10.6 months and median time to progression 6.9 months. Toxicity was substantial with 28% grades III and IV gastro-intestinal toxicity and two early toxic deaths. Conclusions: Based on the lack of response, the substantial toxicity of mainly gastro-intestinal origin and the reported mediocre overall and progression free survival, we cannot advise our short intensive chemoradiotherapy schedule combined with celecoxib as the standard treatment.

  13. Silver-choline chloride modified graphene oxide: Novel nano-bioelectrochemical sensor for celecoxib detection and CCD-RSM model.

    Science.gov (United States)

    Parsaee, Zohreh; Karachi, Nima; Abrishamifar, Seyyed Milad; Kahkha, Mohammad Reza Rezaei; Razavi, Razieh

    2018-07-01

    In this study, silver nanoparticles modified choline chloride functionalized graphene oxide (AgNPs-ChCl-GO) was synthesized using sonochemical method and utilized as a bioelectrochemical sensor for detection of celecoxib (CEL). The characterization studies were ultimately performed in order to acheive a more complete understanding of the morphological and structural features of the AgNPs-ChCl-GO using different techniques including FT-IR, AFM, FE-SEM, EDX, and XRD. AgNPs-ChCl-GO demonstrated a significant improvement in the reduction activity of CEL due to the enhancement in the current response compared to the bare carbon paste electrode (CPE). The optimum experimental conditions, were optimized using central composite design (CCD) methodology. The differential pulse voltammetry (DPVs) showed an expanded linear dynamic ranges of 9.6 × 10 -9 -7.4 × 10 -7  M for celecoxib in Britton-Robinson buffer in pH 5.0 with. LOD (S/N = 3) and LOQ (S/N = 10) were obtained 2.51 × 10 -9  M and 6.58 × 10 -9  M respectively. AgNPs-ChCl-GO-carbon paste electrode exhibited suitable properties and high accuracy determination of celecoxib in the human plasma sample. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Effects of upper respiratory tract illnesses, ibuprofen and caffeine on reaction time and alertness.

    Science.gov (United States)

    Smith, Andrew P; Nutt, David J

    2014-05-01

    Compared with healthy individuals, those with upper respiratory tract illnesses (URTIs) report reduced alertness and have slower reaction times. It is important to evaluate medication that can remove this behavioural malaise. The aim of this study was to compare the effects of a combination of ibuprofen plus caffeine with ibuprofen and caffeine alone, and placebo on malaise associated with URTIs, as measured by psychomotor performance and mood testing. Volunteers were randomly assigned to one of four medication conditions as follows: 200 mg ibuprofen and 100 mg caffeine; 200 mg ibuprofen; 100 mg caffeine; placebo. A single oral dose was given and testing followed for 3 h. Efficacy variables were based on the volunteers' performance, measured by psychomotor performance and mood. The pre-drug results confirmed that those with an URTI had a more negative mood and impaired performance. Results from the simple reaction time task, at both 55- and 110-min post-dosing, showed that a single-dose of caffeinated products (I200/C100 and CAF100) led to significantly faster reaction times than IBU200 and placebo. These effects were generally confirmed with the other performance tasks. Subjective measures showed that the combination of ibuprofen and caffeine was superior to the other conditions. There were no serious adverse events reported, and study medication was well tolerated. The results from the post-drug assessments suggest that a combination of ibuprofen and caffeine was the optimum treatment for malaise associated with URTIs in that it had significant effects on objective performance and subjective measures.

  15. Ibuprofen-loaded poly(trimethylene carbonate-co-ε-caprolactone) electrospun fibres for nerve regeneration.

    Science.gov (United States)

    Pires, Liliana R; Guarino, Vincenzo; Oliveira, Maria J; Ribeiro, Cristina C; Barbosa, Mário A; Ambrosio, Luigi; Pêgo, Ana Paula

    2016-03-01

    The development of scaffolds that combine the delivery of drugs with the physical support provided by electrospun fibres holds great potential in the field of nerve regeneration. Here it is proposed the incorporation of ibuprofen, a well-known non-steroidal anti-inflammatory drug, in electrospun fibres of the statistical copolymer poly(trimethylene carbonate-co-ε-caprolactone) [P(TMC-CL)] to serve as a drug delivery system to enhance axonal regeneration in the context of a spinal cord lesion, by limiting the inflammatory response. P(TMC-CL) fibres were electrospun from mixtures of dichloromethane (DCM) and dimethylformamide (DMF). The solvent mixture applied influenced fibre morphology, as well as mean fibre diameter, which decreased as the DMF content in solution increased. Ibuprofen-loaded fibres were prepared from P(TMC-CL) solutions containing 5% ibuprofen (w/w of polymer). Increasing drug content to 10% led to jet instability, resulting in the formation of a less homogeneous fibrous mesh. Under the optimized conditions, drug-loading efficiency was above 80%. Confocal Raman mapping showed no preferential distribution of ibuprofen in P(TMC-CL) fibres. Under physiological conditions ibuprofen was released in 24 h. The release process being diffusion-dependent for fibres prepared from DCM solutions, in contrast to fibres prepared from DCM-DMF mixtures where burst release occurred. The biological activity of the drug released was demonstrated using human-derived macrophages. The release of prostaglandin E2 to the cell culture medium was reduced when cells were incubated with ibuprofen-loaded P(TMC-CL) fibres, confirming the biological significance of the drug delivery strategy presented. Overall, this study constitutes an important contribution to the design of a P(TMC-CL)-based nerve conduit with anti-inflammatory properties. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Ibuprofen is superior to paracetamol for pain relief following third molar removal.

    Science.gov (United States)

    Ferraiolo, Debra M; Veitz-Keenan, Analia

    2014-12-01

    The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase and the metaRegister of Controlled Trials were searched with no language restrictions. Randomised controlled double-blinded clinical trials using the third molar model were included. Two review authors independently and in duplicate extracted data. The proportion of patients with at least 50% pain relief (based on total pain relief (TOTPAR) and summed pain intensity difference (SPID) data) was calculated for all three drugs at both two and six hours post-dosing and meta-analysed for comparison. Seven studies involving 2241 patients were included. Two studies were considered to be at low risk of bias, three at high risk and two unclear risk of bias. Ibuprofen was found to be a superior analgesic to paracetamol at several doses, with high quality evidence suggesting that ibuprofen 400 mg is superior to 1000 mg paracetamol based on pain relief (estimated from TOTPAR data) and the use of rescue medication meta-analyses. Risk ratio (RR) for at least 50% pain relief (based on TOTPAR) at six hours was 1.47 (95% confidence interval (CI) 1.28 to 1.69; five trials) favouring 400 mg ibuprofen over 1000 mg paracetamol, RR for not using rescue medication (also favouring ibuprofen) was 1.50 (95% CI 1.25 to 1.79; four trials). For combined drug RR for at least 50% of the maximum pain relief over six hours of 1.77 (95% CI 1.32 to 2.39) (paracetamol 1000 mg and ibuprofen 400 mg) (one trial; moderate quality evidence). RR not using rescue medication 1.60 (95% CI 1.36 to 1.88) (two trials; moderate quality evidence). Adverse events were comparable between the treatment groups, but no formal analysis could be undertaken. There is high quality evidence that ibuprofen is superior to paracetamol at doses of 200 mg to 512 mg and 600 mg to 1000 mg respectively based on pain relief and use of rescue medication data collected at six hours postoperatively. The

  17. Ibuprofen versus acetaminophen as a post-partum analgesic for women with severe pre-eclampsia: randomized clinical study.

    Science.gov (United States)

    Vigil-De Gracia, Paulino; Solis, Valentin; Ortega, Nelson

    2017-06-01

    To compare differences in blood pressure levels between patients with severe post-partum pre-eclampsia using ibuprofen or acetaminophen. A randomized controlled trial was made in women with severe pre-eclampsia or superimposed pre-eclampsia after vaginal birth. The patient was randomly selected to receive either 400 mg of ibuprofen every 8 h or 1 g of acetaminophen every 6 h during the post-partum. The primary variable was systolic hypertension ≥150 mmHg and/or diastolic hypertension ≥100 mmHg after the first 24 h post-partum. Secondary variables were the arterial blood pressure readings at 24, 48, 72, and 96 h post-partum and maternal complications. A total of 113 patients were studied: 56 in the acetaminophen group and 57 in the ibuprofen group. With regard to the primary outcome, more cases were significantly hypertensive in the ibuprofen group (36/57; 63.1%) than in the acetaminophen group (16/56; 28.6%). Severe hypertension (≥160/110 mmHg) was not significantly different between the groups, 14.5% (acetaminophen) and 24.5% (ibuprofen). The levels of arterial blood pressure show a hammock-shaped curve independent of the drug used, however, is more noticeable with ibuprofen. This study shows that ibuprofen significantly elevates blood pressure in women with severe pre-eclampsia during the post-partum period.

  18. The effect of ibuprofen on accumulation of indium-111-labeled platelets and leukocytes in experimental myocardial infarction

    International Nuclear Information System (INIS)

    Romson, J.L.; Hook, B.G.; Rigot, V.H.; Schark, M.A.; Swanson, D.P.; Lucchesi, B.R.

    1982-01-01

    To assess the ability of ibuprofen to influence the extent of platelet aggregation and leukocyte infiltration during acute myocardial infarction, autologous indium-111 ( 111 In)-labeled platelets or leukocytes were injected before 60 minutes of left circumflex coronary artery (LCx) occlusion, followed by 24 hours of reperfusion in the canine heart. Myocardial infarct size, as a percent of the area at risk, was reduced in the ibuprofen-treated group (12.5 mg/kg i.v. every 4 hours beginning 30 minutes before LCx occulsion) by 40%, from 48 +/- 4% in control animals to 29 +/- 4% in ibuprofen-treated dogs (p=0.005). Quantification of the platelet-associated 111 In radioactivity in irreversibly injured myocardium indicated that ibuprofen did not alter the accumulation of platelets in infarcted myocardium. In contrast, leukocyte accumulation in infarcted tissue was reduced significantly. In tissue samples with 0.41-0.60 gram infarct, the infarcted/normal ratio of leukocyte radioactivity was 12 +/- 2 in control dogs and 4 +/- 1 in ibuprofen-treated dogs, which represents a 67% reduction in leukocyte accumulation in ibuprofen-treated compared with control dogs. Similar reductions were found in other gram-infarct-weight categories. Although both platelets and leukocytes acumulate in infarcted canine myocardium, ibuprofen may exert its beneficial effect on ischemic myocardium by suppressing the inflammatory response associated with myocardial ischemia and infarction

  19. The effect of ibuprofen on accumulation of 111In-labeled platelets and leukocytes in experimental myocardial infarction

    International Nuclear Information System (INIS)

    Romson, J.L.; Hook, B.G.; Rigot, V.H.; Schork, M.A.; Swanson, D.P.; Lucchesi, B.R.

    1982-01-01

    To assess the ability of ibuprofen to influence the extent of platelet aggregation and leukocyte infiltration during acute myocardial infarction, autologous indium-111 ( 111 In)-labeled platelets or leukocytes were injected before 60 minutes of left circumflex coronary artery (LCx) occlusion, followed by 24 hours of reperfusion in the canine heart. Myocardial infarct size, as a percent of the area at risk, was reduced in the ibuprofen-treated group (12.5 mg/kg i.v. every 4 hours beginning 30 minutes before LCx occlusion) by 40%, from 48 +/- 4% in control animals to 29 +/- 4% in ibuprofen-treated dogs (p . 0.005). Quantification of the platelet-associated 111 In radioactivity in irreversibly injured myocardium indicated that ibuprofen did not alter the accumulation of platelets in infarcted myocardium. In contrast, leukocyte accumulation in infarcted tissue was reduced significantly. In tissue samples with 0.41-0.60 gram infarct, the infarcted/normal ratio of leukocyte radioactivity was 12 +/- 2 in control dogs and 4 +/- 1 in ibuprofen-treated dogs, which represents a 67% reduction in leukocyte accumulation in ibuprofen-treated compared with control dogs. Similar reductions were found in other gram-infarct-weight categories. Although both platelets and leukocytes accumulate in infarcted canine myocardium, ibuprofen may exert its beneficial effect on ischemic myocardium by suppressing the inflammatory response associated with myocardial ischemia and infarction

  20. Ibuprofen exposure in early neonatal life does not affect renal function in young adolescence.

    Science.gov (United States)

    Raaijmakers, Anke; Zhang, Zhen-Yu; Levtchenko, Elena; Simons, Sinno Hp; Cauwenberghs, Nicholas; Heuvel, Lambertus P van den; Jacobs, Lotte; Staessen, Jan A; Allegaert, Karel

    2018-03-01

    Ibuprofen exposure results in acute transient renal dysfunction in preterm neonates, but we are unaware of data on long-term renal safety. In a previously studied cohort of extreme low birth weight (ELBW, ibuprofen. In this post hoc analysis, we linked markers of renal function in young adolescence in ELBW cases with their perinatal (prenatal maternal, setting at birth, treatment modalities including drug prescription during neonatal stay, neonatal creatinine values, postdischarge growth) characteristics, including but not limited to ibuprofen exposure during neonatal stay. Ibuprofen exposure was not associated with significant differences in renal length or eGFR cysC . Moreover, we were unable to identify any other risk factor (perinatal characteristics, postnatal creatinine trends, postdischarge growth) on renal outcome in this cohort. Neonatal exposure to ibuprofen did not affect renal function. Larger studies are needed to explore the confounders of variability in renal function in former ELBW cases. This matters since ELBW relates to risk for hypertension, cardiovascular events and renal disease in later life and identification of risk factors holds the promise of secondary prevention. NCT02147457. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Differing disintegration and dissolution rates, pharmacokinetic profiles and gastrointestinal tolerability of over the counter ibuprofen formulations.

    Science.gov (United States)

    Bjarnason, Ingvar; Sancak, Ozgur; Crossley, Anne; Penrose, Andrew; Lanas, Angel

    2018-02-01

    Formulations of over the counter (OTC) NSAIDs differ substantially, but information is lacking on whether this alters their gastrointestinal profiles. To assess disintegration and dissolution rates and pharmacokinetics of four preparations of OTC ibuprofen and relate these with spontaneously reported gastrointestinal adverse events. Disintegration and dissolution rates of ibuprofen tablets as (a) acid, (b) sodium salt, (c) lysine salt, and (d) as a liquid gelatine capsule were assessed. Pharmacokinetic data gastrointestinal and spontaneously reported adverse events arising from global sales were obtained from files from Reckitt Benckiser. Disintegration at low pH was progressively shorter for the preparations from a-to-d with formation of correspondingly smaller ibuprofen crystals, while dissolution was consistently poor. Dissolution at a neutral pH was least rapid for the liquid gelatine capsule. Pharmacokinetic data showed a shorter t max and a higher C max for preparations b-d as compared with ibuprofen acid. Spontaneously reported abdominal symptoms were rare with the liquid gelatine preparation. The formulations of OTC ibuprofen differ in their disintegration and dissolution properties, pharmacokinetic profiles and apparent gastrointestinal tolerability. Spontaneously reported abdominal symptoms were five times lower with the liquid gelatine capsule as compared with ibuprofen acid despite a 30% increase in C max . © 2017 Royal Pharmaceutical Society.

  2. Comparative study of sustained-release lipid microparticles and solid dispersions containing ibuprofen

    Directory of Open Access Journals (Sweden)

    Hugo Almeida

    2012-09-01

    Full Text Available Ibuprofen is one of the most important non-steroidal anti-inflammatory drugs used in the treatment of inflammatory diseases. In its pure state, ibuprofen presents poor physical and mechanical characteristics and its use in solid dosage forms needs the addition of excipients that improve these properties. The selection of the best excipients and the most suitable pharmaceutical dosage form to carry ibuprofen is very important for the industrial success of this drug. Given these factors, lipid microparticles and solid dispersions of ibuprofen with cetyl alcohol, stearic acid, and hydrogenated castor oil were prepared. These formulations were intended to improve the physical and mechanical characteristics and to sustain the release of this drug. Physical mixtures were also prepared with the same ingredients in similar proportions. The solid dispersions of ibuprofen/stearic acid and ibuprofen/hydrogenated castor oil showed the best flow characteristics compared with pure ibuprofen. Further, gelatin capsules filled with lipid microparticles and solid dispersions were submitted to dissolution tests in order to study the influence of the prepared systems in the release profiles of ibuprofen. Prolonged release of ibuprofen was achieved with the lipid microparticles and solid dispersions prepared with the different types of excipients.O ibuprofeno é um dos antiinflamatórios não esteróides mais utilizados no tratamento de patologias associadas a processos inflamatórios. Este fármaco, quando no seu estado puro, apresenta características físicas e mecânicas pouco satisfatórias e a sua utilização em formas sólidas só é possível se forem adicionados excipientes que permitam melhorar estas propriedades. A seleção dos excipientes ideais e da forma farmacêutica mais adequada para veicular o ibuprofeno é fundamental para o sucesso industrial deste fármaco. Tendo em conta estes fatores, prepararam-se micropartículas lipídicas e dispersões s

  3. Cyclic resolution of racemic ibuprofen via coupled efficient lipase and acid-base catalysis.

    Science.gov (United States)

    Liu, Ying; Wang, Fang; Tan, Tianwei

    2009-03-01

    Extracellular lipase LIP prepared in our lab from the yeast Yarrowia lipolytica was used for the resolution of racemic ibuprofen. The (S)-enantiomer was preferred by lipase LIP, and the unreacted (R)-enantiomer was extracted and racemized in basic solvent-water medium to be re-resolved. Solvent, content of solvent, base concentration, and temperature have a strong effect on racemization. The (S)-ester was separated and hydrolyzed to (S)-ibuprofen in acidic dimethyl sulfoxide-water mixture containing 70% dimethyl sulfoxide. The high purity (S)-ibuprofen (ee = 0.98) was obtained using lipase LIP to catalyze hydrolysis of (S)-ester in 0.1 M phosphate buffer (pH = 8). (c) 2008 Wiley-Liss, Inc.

  4. Ibuprofen ingestion does not affect markers of post-exercise muscle inflammation.

    Directory of Open Access Journals (Sweden)

    Luke eVella

    2016-03-01

    Full Text Available Purpose: We investigated if oral ingestion of ibuprofen influenced leucocyte recruitment and infiltration following an acute bout of traditional resistance exercise. Methods: Sixteen male subjects were divided into two groups that received the maximum over-the-counter dose of ibuprofen (1200 mg d-1 or a similarly administered placebo following lower body resistance exercise. Muscle biopsies were taken from m.vastus lateralis and blood serum samples were obtained before and immediately after exercise, and at 3 h and 24 h after exercise. Muscle cross-sections were stained with antibodies against neutrophils (CD66b and MPO and macrophages (CD68. Muscle damage was assessed via creatine kinase and myoglobin in blood serum samples, and muscle soreness was rated on a ten-point pain scale. Results: The resistance exercise protocol stimulated a significant increase in the number of CD66b+ and MPO+ cells when measured 3 h post exercise. Serum creatine kinase, myoglobin and subjective muscle soreness all increased post-exercise. Muscle leucocyte infiltration, creatine kinase, myoglobin and subjective muscle soreness were unaffected by ibuprofen treatment when compared to placebo. There was also no association between increases in inflammatory leucocytes and any other marker of cellular muscle damage. Conclusion: Ibuprofen administration had no effect on the accumulation of neutrophils, markers of muscle damage or muscle soreness during the first 24 h of post-exercise muscle recovery.

  5. The cardiovascular safety of non-steroidal anti-inflammatory drugs (NSAIDs) among healthy people - A nationwide population study

    DEFF Research Database (Denmark)

    Fosbøl, Emil Loldrup

    2010-01-01

    1,63 CI: 1,52-1,76) var forbundet med en øget risiko for hjertedød, og artiklen konkluderer, at alle mennesker bør vise forsigtighed ved brugen af disse lægemidler. Brug af ibuprofen (HR 1,01 CI: 0,96-1,07) eller naproxen (HR 0,97 CI: 0,83-1,12) er et tilsyneladende sikrere alternativ hvad angår den...... til kardiovasculær død eller fatalt eller non-fatalt stroke. Ibuprofen viste lignende resultater som for celecoxib hvorimod naproxen ikke var associeret med øget kardiovaskulær risiko. KONKLUSION Overordnet konkluderer afhandlingen, at nogle NSAID er forbundet med øget risiko for kardiovaskulær...

  6. Preparation, Characterization and Optimization of Ibuprofen ...

    African Journals Online (AJOL)

    Purpose: To develop an ibuprofen ointment with a potential for both topical and systemic delivery of the drug. Method: A co-solvency technique with a trial and error approach was used to develop a 10% ibioprofen ointment in petrolatum base, with the entire drug dissolved in the base. An insertion cell was used to evaluate ...

  7. The comparison between effect of chemoradiation with weekly cisplatin with or without celecoxib in treatment of nasopharyngeal carcinoma: A phase III clinical trial

    Directory of Open Access Journals (Sweden)

    Mohamad Mohammadianpanah

    2009-07-01

    Full Text Available Introduction: Concurrent cisplatin-based chemoradiation is currently considered the treatment of choice for locoregional nasopharyngeal carcinoma. Celecoxib is a selective cyclooxygenase-2 (COX-2 inhibitor which can potentially enhance the effect of radiotherapy. The aim of this study was to determine the efficacy and safety of celecoxib in nasopharyngeal carcinoma. Materials and Methods: Patients with newly diagnosed locoregional nasopharyngeal carcinoma were included in this clinical trial study. The patients were assigned to receive 7 weeks concurrent chemoradiation with weekly cisplatin and either celecoxib 100 mg twice daily or placebo. After completion of chemoradiation, all patients received combined chemotherapy with cisplatin plus 5-Fu every 3 weeks for 3 cycles. Clinical response rates and treatment-related toxicity were the primary and secondary end-point of the study. Results: Total of 50 eligible patients with the median age of 43 years were enrolled in the trial. Overall (complete and partial clinical response rate was 100% in both groups. Complete and partial clinical response rates were 64% and 36% in study group and 44% and 56% in control group respectively (P>0.25. There was no difference in terms of treatment-related toxicity rates between two groups. Conclusions: This clinical trial showed that addition of celecoxib 100 mg twice daily to concurrent chemoradiation does not increase the response rates and treatment-related toxicities in patients with locoregional nasopharyngeal carcinoma.

  8. Ibuprofen-induced patent ductus arteriosus closure: physiologic, histologic, and biochemical effects on the premature lung.

    Science.gov (United States)

    McCurnin, Donald; Seidner, Steven; Chang, Ling-Yi; Waleh, Nahid; Ikegami, Machiko; Petershack, Jean; Yoder, Brad; Giavedoni, Luis; Albertine, Kurt H; Dahl, Mar Janna; Wang, Zheng-ming; Clyman, Ronald I

    2008-05-01

    The goal was to study the pulmonary, biochemical, and morphologic effects of a persistent patent ductus arteriosus in a preterm baboon model of bronchopulmonary dysplasia. Preterm baboons (treated prenatally with glucocorticoids) were delivered at 125 days of gestation (term: 185 days), given surfactant, and ventilated for 14 days. Twenty-four hours after birth, newborns were randomly assigned to receive either ibuprofen (to close the patent ductus arteriosus; n = 8) or no drug (control; n = 13). After treatment was started, the ibuprofen group had significantly lower pulmonary/systemic flow ratio, higher systemic blood pressure, and lower left ventricular end diastolic diameter, compared with the control group. There were no differences in cardiac performance indices between the groups. Ventilation index and dynamic compliance were significantly improved with ibuprofen. The improved pulmonary mechanics in ibuprofen-treated newborns were not attributable to changes in levels of surfactant protein B, C, or D, saturated phosphatidylcholine, or surfactant inhibitory proteins. There were no differences in tracheal concentrations of cytokines commonly associated with the development of bronchopulmonary dysplasia. The groups had similar messenger RNA expression of genes that regulate inflammation and remodeling in the lung. Lungs from ibuprofen-treated newborns were significantly drier (lower wet/dry ratio) and expressed 2.5 times more epithelial sodium channel protein than did control lungs. By 14 days after delivery, control newborns had morphologic features of arrested alveolar development (decreased alveolar surface area and complexity), compared with age-matched fetuses. In contrast, there was no evidence of alveolar arrest in the ibuprofen-treated newborns. Ibuprofen-induced patent ductus arteriosus closure improved pulmonary mechanics, decreased total lung water, increased epithelial sodium channel expression, and decreased the detrimental effects of preterm birth

  9. Ibuprofen enhances the anticancer activity of cisplatin in lung cancer cells by inhibiting the heat shock protein 70

    Science.gov (United States)

    Endo, H; Yano, M; Okumura, Y; Kido, H

    2014-01-01

    Hsp70 is often overexpressed in cancer cells, and the selective cellular survival advantage that it confers may contribute to the process of tumour formation. Thus, the pharmacological manipulation of Hsp70 levels in cancer cells may be an effective means of preventing the progression of tumours. We found that the downregulation of Hsp70 by ibuprofen in vitro enhances the antitumoural activity of cisplatin in lung cancer. Ibuprofen prominently suppressed the expression of Hsp70 in A549 cells derived from lung adenocarcinoma and sensitized them to cisplatin in association with an increase in the mitochondrial apoptotic cascade, whereas ibuprofen alone did not induce cell death. The cisplatin-dependent events occurring up- and downstream of mitochondrial disruption were accelerated by treatment with ibuprofen. The increase in cisplatin-induced apoptosis caused by the depletion of Hsp70 by RNA interference is evidence that the increased apoptosis by ibuprofen is mediated by its effect on Hsp70. Our observations indicate that the suppression of Hsp70 by ibuprofen mediates the sensitivity to cisplatin by enhancing apoptosis at several stages of the mitochondrial cascade. Ibuprofen, therefore, is a potential therapeutic agent that might allow lowering the doses of cisplatin and limiting the many challenge associated with its toxicity and development of drug resistance. PMID:24481441

  10. Efficacy and Safety of Ibuprofen in Infants Aged Between 3 and 6 Months.

    Science.gov (United States)

    Ziesenitz, Victoria C; Zutter, Andreas; Erb, Thomas O; van den Anker, Johannes N

    2017-08-01

    Ibuprofen is a non-steroidal anti-inflammatory drug frequently administered to children of various ages for relief of fever and pain and is approved as an over-the-counter medication in many countries worldwide. Although there are extensive data on its efficacy and safety in children and adults, there are divergent dosing recommendations for analgesia and treatment of fever in infants, especially in the age group between 3 and 6 months of age. In this article, we have assessed the safety and efficacy of ibuprofen use in infants in an attempt to find the optimal method of pain and fever management in this specific age group. Based on the current evidence, short-term use of ibuprofen is considered safe in infants older than 3 months of age having a body weight above 5-6 kg when special attention is given to the hydration of the patient. Ibuprofen should be prescribed based on body weight using a dose of 5-10 mg/kg. This dose can be administered 3-4 times a day resulting in a maximum total daily dose of 30-40 mg/kg. The rectal route has been shown to be less reliable because of erratic absorption, especially in young infants. Since most efficacy and safety data have been derived from trials in infants with fever, future studies should focus on the efficacy of ibuprofen in young infants with pain.

  11. Ibuprofen-associated acute kidney injury in dehydrated children with acute gastroenteritis.

    Science.gov (United States)

    Balestracci, Alejandro; Ezquer, Mauricio; Elmo, María Eugenia; Molini, Andrea; Thorel, Claudia; Torrents, Milagros; Toledo, Ismael

    2015-10-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) induce acute kidney injury (AKI) in volume-depleted patients; however the prevalence of this complication is likely underestimated. We assessed the impact of ibuprofen exposure on renal function among dehydrated children with acute gastroenteritis (AGE) to further characterize NSAID-associated AKI. Over a 1-year period dehydrated children with AGE (n = 105) were prospectively enrolled and grouped as cases, presenting with AKI (n = 46) or controls, not presenting with AKI (n = 59). AKI was defined by pediatric RIFLE (pRIFLE) criteria. Among the children enrolled in the study, AKI prevalence was 44 %, and 34 (54 %) of the 63 patients who received ibuprofen developed renal impairment. Relative to the controls, children presenting with AKI were younger (median age 0.66 vs. 1.74 years; p dehydration, ibuprofen exposure remained an independent risk factor for AKI (p dehydrated children with AGE. Drug exposure increased the risk for developing AKI by more than twofold, independent of the magnitude of the dehydration.

  12. An unusual finding of massive pulmonary embolism in a patient during treatment with high-dose ibuprofen.

    Science.gov (United States)

    Bilora, Franca; Adamo, Angelo; Pomerri, Fabio; Prandoni, Paolo

    2016-02-01

    Non-steroidal anti-inflammatory drugs have been associated with an increased risk of venous thromboembolism. We report for the first time, the case of a patient who developed massive pulmonary embolism after a long period of treatment with high doses of ibuprofen. A 65-year-old woman was admitted with severe dyspnea while on treatment with high doses of ibuprofen for diffuse spine pain due to arthrosis. A spiral computed tomography showed a massive pulmonary embolism. No other explanation for the thromboembolic disorder was found. She was successfully treated with therapeutic doses of low-molecular-weight heparin followed by rivaroxaban. Ibuprofen was discontinued and replaced by tramadol. High-dose ibuprofen is likely to have accounted for the life-threatening thromboembolic disorder.

  13. IBUPROFEN AS A MEDICATION FOR A CORRECTION OF SYMPTOMS OF NORMAL VACCINAL PROCESS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    T.A. Chebotareva

    2008-01-01

    Full Text Available The pathogenetic approach to treatment of symptoms of normal vaccinal process in children after standard vaccination, based on the results of application of anti9inflammatory medications — ibuprofen (nurofen for children and paracetamol is presented in this article. Clinical activity of ibuprofen was established on the basis of clinica catamnestic observation of 856 vaccinated children aged from 3 months to 3 years. recommendations for application of these medications as a treatment for a correction of vaccinal reactions are given.Key words: children, ibuprofen, paracetamol, vaccination.

  14. Effectiveness of Ibuprofen Administration on the Depth of Anesthesia in Inflamed Teeth

    Directory of Open Access Journals (Sweden)

    R Mahmodi

    2006-07-01

    Full Text Available Introduction: Incomplete anesthesia of inflamed teeth is a well known clinical occurrence and the purpose of this study was to evaluate the effectiveness of Ibuprofen as a premedication in improving the quality of anesthesia in patients with inflamed teeth pulps. Methods: Forty patients with the diagnosis of irreversible pulpitis in one mandibular tooth were selected. Two other teeth in the same quadrant were selected as controls. Electric pulp tester (EPT was used in this study to evaluate the quality of anesthesia. The subjects were divided into two groups randomly, and after recording of pulp tester response in each group, one of the two drugs; ibuprofen or placebo was administered 1 hour prior to anesthesia injection. After injection, EPT measurement was recorded. The reversed EPT scale was used for evaluation of the depth of anesthesia. Results : Data was analyzed to statistically compare the results before and after anesthesia and drug administration in cases and control group .Significantly lower TSLs were observed in the ibuprofen group (Pvalue= 0.001. Conclusion: This study concluded that preoperative administration of ibuprofen (if not contraindicated 1 hour before local anesthesia injection is an effective method for achieving deep anesthesia during RCT of teeth with irreversible pulpitis.

  15. Ibuprofen versus Acetaminophen in Controlling Postoperative Impacted Third Molar Tooth Extraction Pain

    International Nuclear Information System (INIS)

    Khan, I.; Bukhari, S. G. A.; Ahmad, W.; Rubbab,; Junaid, M.

    2013-01-01

    Objectives: To compare the efficacy of ibuprofen and acetaminophen in reducing postoperative third molar extraction pain in patients reporting to Armed Forces Institute of Dentistry. Study design: Randomized controlled trial. Place and duration of study: The study was carried out on patients who presented for surgical removal of impacted teeth at Armed Forces Institute of Dentistry Rawalpindi (AFID) from February 2008 to March 2--9 at the Department of Oral Surgery, Armed Forces Institute of Dentistry Rawalpindi. Patients and methods: One hundred and forty patients requiring surgical removal of mandibular impacted teeth were equally divided into two groups. Surgical extraction of third molar tooth was performed under local anesthesia. Patients in group A were given ibuprofen and in group B were given acetaminophen at 6 hourly intervals. First dose was given 3 hours postoperatively. Each patient rated pain on a visual analog scale at baseline and then at 12, 24, 48 and 72 hours postoperatively. Results: There was statistically significant difference (p=0.025) during first 12 hours with ibuprofen group showing better efficacy but afterwards there was no significant difference in the efficacy of both drugs. Conclusions: Ibuprofen is more effective in controlling severe third molar extraction pain as compared to acetaminophen but has similar efficacy in controlling moderate pain. (author)

  16. Release behavior and intra-articular biocompatibility of celecoxib-loaded acetyl-capped PCLA-PEG-PCLA thermogels

    NARCIS (Netherlands)

    Petit, Audrey|info:eu-repo/dai/nl/371748461; Sandker, Marjan; Müller, Benno; Meyboom, Ronald; van Midwoud, Paul; Bruin, Peter; Redout, Everaldo M; Versluijs-Helder, Marjan|info:eu-repo/dai/nl/311472699; van der Lest, Chris H A; Buwalda, Sytze J|info:eu-repo/dai/nl/339146850; de Leede, Leo G J; Vermonden, Tina|info:eu-repo/dai/nl/275124517; Kok, Robbert Jan|info:eu-repo/dai/nl/170678326; Weinans, Harrie; Hennink, Wim E|info:eu-repo/dai/nl/070880409

    In this study, we investigated the in vitro and in vivo properties and performance of a celecoxib-loaded hydrogel based on a fully acetyl-capped PCLA-PEG-PCLA triblock copolymer. Blends of different compositions of celocoxib, a drug used for pain management in osteoarthritis, and the acetyl-capped

  17. Optimisation of cosolvent concentration for topical drug delivery III--influence of lipophilic vehicles on ibuprofen permeation.

    Science.gov (United States)

    Watkinson, R M; Guy, R H; Oliveira, G; Hadgraft, J; Lane, M E

    2011-01-01

    Previously, we have reported the effects of water, ethanol, propylene glycol and various binary and ternary mixtures of these solvents on the permeation of ibuprofen in model membranes and in skin. The present study investigates the influence of lipophilic vehicles on the transport of ibuprofen in silicone membrane and in human skin. The permeation of ibuprofen was measured from mineral oil (MO), Miglyol® 812 (MG) and binary mixtures of MO and MG. The solubility of ibuprofen was 5-fold higher in MG than in MO, however, the permeation of ibuprofen from the pure vehicles and combinations of both was comparable in silicone membrane. Additionally, there were no significant differences in skin permeation for MO and MG vehicles. When the permeation of various hydrophilic and lipophilic vehicles is considered, a trend between flux values for the model membrane and skin is evident (r(2) = 0.71). The findings suggest that silicone membrane may provide information on qualitative trends in skin permeation for vehicles of diverse solubility and partition characteristics. Copyright © 2010 S. Karger AG, Basel.

  18. Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib

    DEFF Research Database (Denmark)

    Macdonald, Thomas M; Hawkey, Chris J; Ford, Ian

    2017-01-01

    BACKGROUND: Selective cyclooxygenase-2 inhibitors and conventional non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) have been associated with adverse cardiovascular (CV) effects. We compared the CV safety of switching to celecoxib vs. continuing nsNSAID therapy in a European setting...

  19. Ibuprofen versus steroids: risk and benefit, efficacy and safety

    Directory of Open Access Journals (Sweden)

    M. Giovannini

    2013-10-01

    Full Text Available In the last few years we have observed an upward trend in the employment of ibuprofen as anti-inflammatory and antipyretic therapy. Therefore the pediatrician has often a precious option in the anti-inflammatory and antipyretic treatment in children instead of using steroids and paracetamol. In clinical practice ibuprofen can be used in the treatment of headache, toothache, otalgy, dysmenorrhea, neuralgia, arthralgia, myalgia, abdominal pain and fever: it is the first choice for these common diseases. However, the use of steroids is a routine, even if non-corticosteroid anti-inflammatory molecules could be useful. Certainly steroids are powerful anti-inflammatory, indicated for the treatment of chronic inflammatory disorders and in acute respiratory and allergic diseases. Beside, thanks to their chemical and pharmacological profile, they also provide patients with an antipyretic effect. However, the use of steroids must be reserved to cases in which other classical antipyretics such as non-steroidal anti-inflammatory drugs are not effective. The possible side effects and risks associated with stepping down steroids must be considered. Although “steroids-phobia” should be discouraged, steroids are to be reserved only as the first indication. In all other cases the pediatrician can use ibuprofen, whose efficacy and safety are widely demonstrated by now.

  20. Thermodynamics of chiral selectivity in capillary electrophoresis : separation of ibuprofen enantiomers with beta-cyclodextrin

    NARCIS (Netherlands)

    Reijenga, J.C.; Ingelse, B.A.; Everaerts, F.M.

    1997-01-01

    The effect of temperature on the electrophoretic chiral separation of ibuprofen with ß-CD was investigated. Background electrolytes with sodium acetate or formate were chosen because of their constant pK within 0.03 units in the temperature range 25–50°C. Ibuprofen has a temperature independent pK

  1. Self-Microemulsifying Drug Delivery System: Formulation and Study Intestinal Permeability of Ibuprofen in Rats

    Directory of Open Access Journals (Sweden)

    Bharat Bhushan Subudhi

    2013-01-01

    Full Text Available The study was aimed at developing a self-microemulsifying drug delivery system (SMEDDS of Ibuprofen for investigating its intestinal transport behavior using the single-pass intestinal perfusion (SPIP method in rat. Methods. Ibuprofen loaded SMEDDS (ISMEDDS was developed and was characterized. The permeability behavior of Ibuprofen over three different concentrations (20, 30, and 40 µg/mL was studied in each isolated region of rat intestine by SPIP method at a flow rate of 0.2 mL/min. The human intestinal permeability was predicted using the Lawrence compartment absorption and transit (CAT model since effective permeability coefficients (Peff values for rat are highly correlated with those of human, and comparative intestinal permeability of Ibuprofen was carried out with plain drug suspension (PDS and marketed formulation (MF. Results. The developed ISMEDDS was stable, emulsified upon mild agitation with 44.4 nm ± 2.13 and 98.86% ± 1.21 as globule size and drug content, respectively. Higher Peff in colon with no significant Peff difference in jejunum, duodenum, and ileum was observed. The estimated human absorption of Ibuprofen for the SMEDDS was higher than that for PDS and MF (P<0.01. Conclusion. Developed ISMEDDS would possibly be advantageous in terms of minimized side effect, increased bioavailability, and hence the patient compliance.

  2. Overview review: Comparative efficacy of oral ibuprofen and paracetamol (acetaminophen) across acute and chronic pain conditions.

    Science.gov (United States)

    Moore, R A; Derry, S; Wiffen, P J; Straube, S; Aldington, D J

    2015-10-01

    Ibuprofen and paracetamol have long been used as analgesics in a range of acute, intermittent and chronic pain conditions. Paracetamol is often the first line analgesic recommended, without consensus about which is the better analgesic. An overview review of systematic reviews and meta-analyses directly compares ibuprofen and paracetamol at standard doses in particular painful conditions, or uses indirect comparisons against placebo. Electronic searches for systematic reviews were sought published since 1995 using outcomes approximating to ≥50% pain intensity reduction. Painful conditions were acute post-operative pain, dysmenorrhoea, tension-type headache (TTH), migraine, osteoarthritis and rheumatoid arthritis, back pain, cancer and paediatric pain. There was no systematic assessment of harm. Sixteen systematic reviews and four individual patient data meta-analyses were included. Ibuprofen was consistently superior to paracetamol at conventional doses in a range of painful conditions. Two direct comparisons favoured ibuprofen (acute pain, osteoarthritis). Three of four indirect comparisons favoured ibuprofen (acute pain, migraine, osteoarthritis); one showed no difference (TTH), although there were methodological problems. In five pain conditions (dysmenorrhoea, paediatric pain, cancer pain, back pain and rheumatoid arthritis), there were limited data on paracetamol and ibuprofen. At standard doses in different painful conditions, ibuprofen was usually superior producing more patients with the degree of pain relief that patients feel worthwhile. Neither of the drugs will be effective for everyone, and both are needed. This overview questions the practice of routinely using paracetamol as a first line analgesic because there is no good evidence for efficacy of paracetamol in many pain conditions. © 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFICC®.

  3. Ibuprofen analysis in blood samples by palladium particles-impregnated sodium montmorillonite electrodes: Validation using high performance liquid chromatography.

    Science.gov (United States)

    Loudiki, A; Boumya, W; Hammani, H; Nasrellah, H; El Bouabi, Y; Zeroual, M; Farahi, A; Lahrich, S; Hnini, K; Achak, M; Bakasse, M; El Mhammedi, M A

    2016-12-01

    The electrochemical detection of ibuprofen has been studied on Palladium-Montmorillonite (Mt) modified carbon paste electrode using differential pulse voltammetry. The optimization of the modifier preparation and the instrumental parameters was investigated. The results indicate that ibuprofen oxidation was favored in the presence of Pd-PdO particles. The quantitative determination of ibuprofen was statistically analyzed and validated using HPLC method. The detection and quantification limits, specificity and precision were found to be acceptable. Finally, the developed method was successfully applied for ibuprofen determination in human blood samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Grafting of allylimidazole and n-vinylcaprolactam as a thermosensitive polymer onto magnetic nano-particles for the extraction and determination of celecoxib in biological samples.

    Science.gov (United States)

    Morovati, Atefeh; Ahmad Panahi, Homayon; Yazdani, Farzaneh

    2016-11-20

    In this research, a novel method is reported for the surface grafting of n-vinylcaprolactam as a thermosensitive agent and allylimidazole with affinity toward celecoxib onto magnetic nano-particles. The grafted nano-particles were characterized by Fourier transform infrared spectroscopy, elemental analysis, and thermogravimetric analysis. The surface morphology was studied using Scanning Electron Microscopy. The resulting grafted nano-particles were used for the determination of trace celecoxib in biological human fluids and pharmaceutical samples. The profile of celecoxib uptake by the modified magnetic nano-particles indicated good accessibility of the active sites in the grafted copolymer. It was found that the adsorption behavior could be fitted by the Langmuir adsorption isotherm model. Solid phase extraction for biological fluids such as urine and serum were investigated. In this study, urine extraction recovery of more than 95% was obtained. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Ibuprofen slows migration and inhibits bowel colonization by enteric nervous system precursors in zebrafish, chick and mouse

    Science.gov (United States)

    Schill, Ellen Merrick; Lake, Jonathan I.; Tusheva, Olga A.; Nagy, Nandor; Bery, Saya K.; Foster, Lynne; Avetisyan, Marina; Johnson, Stephen L.; Stenson, William F.; Goldstein, Allan M.; Heuckeroth, Robert O.

    2016-01-01

    Hirschsprung Disease (HSCR) is a potentially deadly birth defect characterized by the absence of the enteric nervous system (ENS) in distal bowel. Although HSCR has clear genetic causes, no HSCR-associated mutation is 100% penetrant, suggesting gene-gene and gene-environment interactions determine HSCR occurrence. To test the hypothesis that certain medicines might alter HSCR risk we treated zebrafish with medications commonly used during early human pregnancy and discovered that ibuprofen caused HSCR-like absence of enteric neurons in distal bowel. Using fetal CF-1 mouse gut slice cultures, we found that ibuprofen treated enteric neural crest-derived cells (ENCDC) had reduced migration, fewer lamellipodia and lower levels of active RAC1/CDC42. Additionally, inhibiting ROCK, a RHOA effector and known RAC1 antagonist, reversed ibuprofen effects on migrating mouse ENCDC in culture. Ibuprofen also inhibited colonization of Ret+/− mouse bowel by ENCDC in vivo and dramatically reduced bowel colonization by chick ENCDC in culture. Interestingly, ibuprofen did not affect ENCDC migration until after at least three hours of exposure. Furthermore, mice deficient in Ptgs1 (COX 1) and Ptgs2 (COX 2) had normal bowel colonization by ENCDC and normal ENCDC migration in vitro suggesting COX-independent effects. Consistent with selective and strain specific effects on ENCDC, ibuprofen did not affect migration of gut mesenchymal cells, NIH3T3, or WT C57BL/6 ENCDC, and did not affect dorsal root ganglion cell precursor migration in zebrafish. Thus, ibuprofen inhibits ENCDC migration in vitro and bowel colonization by ENCDC in vivo in zebrafish, mouse and chick, but there are cell type and strain specific responses. These data raise concern that ibuprofen may increase Hirschsprung disease risk in some genetically susceptible children. PMID:26586201

  6. Effects of Ibuprofen and Resistance Training on Bone and Muscle: A Randomized Controlled Trial in Older Women.

    Science.gov (United States)

    Duff, Whitney R D; Chilibeck, Philip D; Candow, Darren G; Gordon, Julianne J; Mason, Riley S; Taylor-Gjevre, Regina; Nair, Bindu; Szafron, Michael; Baxter-Jones, Adam; Zello, Gordon A; Kontulainen, Saija A

    2017-04-01

    Resistance training with ibuprofen supplementation may improve musculoskeletal health in postmenopausal women. The study purpose was to determine the efficacy of resistance training and ibuprofen supplementation on bone and muscle properties in postmenopausal women. Participants (n = 90, 65.3 ± 4.9 yr) were randomly assigned to: supervised resistance training or stretching (placebo-exercise) with postexercise ibuprofen (400 mg) or placebo supplementation for 3 d·wk (9 months). Baseline and postintervention measurements included distal and shaft scans of the forearm and lower leg using peripheral quantitative computed tomography. Distal site outcomes included cross-sectional area, content, and density for total and trabecular bone, as well as estimated bone strength in compression. Shaft site outcomes included total bone area; cortical bone area, content, and density; estimated bone strength in torsion; and muscle area and density. Exercise-supplement-time interactions for total bone content at the distal radius (P = 0.009) and cortical density at the radius shaft (P = 0.038) were significant. Resistance training with ibuprofen decreased total bone content (-1.5%) at the distal radius in comparison to the resistance training (0.6%; P = 0.032) and ibuprofen alone (0.5%; P = 0.050). Change in cortical density at the radius shaft differed between the stretching with placebo and ibuprofen supplementation groups (-1.8% vs 1.1%; P = 0.050). Resistance training preserved muscle density in the lower leg more so than stretching (-3.1% vs -5.4%; P = 0.015). Ibuprofen consumed immediately after resistance training had a deleterious effect on bone mineral content at the distal radius, whereas resistance training or ibuprofen supplementation individually prevented bone loss. Resistance training prevented muscle density decline in the lower leg.

  7. Efficacy and safety of concurrent chemoradiation with weekly cisplatin ± low-dose celecoxib in locally advanced undifferentiated nasopharyngeal carcinoma: a phase II-III clinical trial.

    Science.gov (United States)

    Mohammadianpanah, Mohammad; Razmjou-Ghalaei, Sasan; Shafizad, Amin; Ashouri-Taziani, Yaghoub; Khademi, Bijan; Ahmadloo, Niloofar; Ansari, Mansour; Omidvari, Shapour; Mosalaei, Ahmad; Mosleh-Shirazi, Mohammad Amin

    2011-01-01

    This is the first study that aimed to determine the efficacy and safety of concurrent chemoradiation with weekly cisplatin ± celecoxib 100 mg twice daily in locally advanced undifferentiated nasopharyngeal carcinoma. Eligible patients had newly diagnosed locally advanced (T3-T4, and/or N2-N3, M0) undifferentiated nasopharyngeal carcinoma, no prior therapy, Karnofsky performance status ≥ 70, and normal organ function. The patients were assigned to receive 7 weeks concurrent chemoradiation (70 Gy) with weekly cisplatin 30 mg/m 2 with either celecoxib 100 mg twice daily, (study group, n = 26) or placebo (control group, n = 27) followed by adjuvant combined chemotherapy with cisplatin 70 mg/m 2 on day 1 plus 5-fluorouracil 750 mg/m 2 /d with 8-h infusion on days 1-3, 3-weekly for 3 cycles. Overall clinical response rate was 100% in both groups. Complete and partial clinical response rates were 64% and 36% in the study group and 44% and 56% in the control group, respectively (P > 0.25). The addition of celecoxib to concurrent chemoradiation was associated with improved 2-year locoregional control rate from 84% to 100% (P = 0.039). The addition of celecoxib 100 mg twice daily to concurrent chemoradiation improved 2-year locoregional control rate.

  8. A Randomized Placebo Controlled Trial of Ibuprofen for Respiratory Syncytial Virus Infection in a Bovine Model

    Science.gov (United States)

    Walsh, Paul; Behrens, Nicole; Carvallo Chaigneau, Francisco R.; McEligot, Heather; Agrawal, Karan; Newman, John W.; Anderson, Mark; Gershwin, Laurel J.

    2016-01-01

    Background Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to the virus. RSV is accompanied by elevated prostaglandin E2 (PGE2) which is followed by neutrophil led inflammation in the lung. Ibuprofen is a prototypical non-steroidal anti-inflammatory drug that decreases PGE2 levels by inhibiting cyclooxygenase. Hypotheses We hypothesized that treatment of RSV with ibuprofen would decrease PGE2 levels, modulate the immune response, decrease clinical illness, and decrease the histopathological lung changes in a bovine model of RSV. We further hypothesized that viral replication would be unaffected. Methods We performed a randomized placebo controlled trial of ibuprofen in 16 outbred Holstein calves that we infected with RSV. We measured clinical scores, cyclooxygenase, lipoxygenase and endocannabinoid products in plasma and mediastinal lymph nodes and interleukin (Il)-4, Il-13, Il-17 and interferon-γ in mediastinal lymph nodes. RSV shedding was measured daily and nasal Il-6, Il-8 and Il-17 every other day. The calves were necropsied on Day 10 post inoculation and histology performed. Results One calf in the ibuprofen group required euthanasia on Day 8 of infection for respiratory distress. Clinical scores (pibuprofen group. Ibuprofen decreased cyclooxygenase, lipoxygenase, and cytochrome P450 products, and increased monoacylglycerols in lung lymph nodes. Ibuprofen modulated the immune response as measured by narrowed range of observed Il-13, Il-17 and IFN-γ gene expression in mediastinal lymph nodes. Lung histology was not different between groups, and viral shedding was increased in calves randomized to ibuprofen. Conclusions Ibuprofen decreased PGE2, modulated the immune response, and improved clinical outcomes. However lung

  9. Ibuprofen delivered by poly(lactic-co-glycolic acid (PLGA nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations

    Directory of Open Access Journals (Sweden)

    Bonelli P

    2012-11-01

    Full Text Available Patrizia Bonelli,1 Franca M Tuccillo,1 Antonella Federico,5 Maria Napolitano,2 Antonella Borrelli,1 Daniela Melisi,6 Maria G Rimoli,6 Raffaele Palaia,3 Claudio Arra,4 Francesco Carinci71Laboratory of Molecular Biology and Viral Oncogenesis; 2Department of Clinical Immunology; 3Department of Gastrointestinal-Hepatobiliary-Pancreatic Cancer Oncology Surgery; 4Animal Facility, National Cancer Institute G Pascale, Naples, Italy; 5Microtech Laboratory, Naples, Italy; 6Pharmaceutical and Toxicological Chemistry Department, School of Pharmacy, University "Federico II", Naples, Italy; 7Department of Maxillofacial Surgery, University of Ferrara, Ferrara, ItalyPurpose: Epidemiological, clinical, and laboratory studies have suggested that ibuprofen, a commonly used nonsteroidal anti-inflammatory drug, inhibits the promotion and proliferation of certain tumors. Recently, we demonstrated the antiproliferative effects of ibuprofen on the human gastric cancer cell line MKN-45. However, high doses of ibuprofen were required to elicit these antiproliferative effects in vitro. The present research compared the antiproliferative effects of ibuprofen delivered freely and released by poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs in MKN-45 cells.Methods: MKN-45 human gastric adenocarcinoma cells were treated with ibuprofen-loaded PLGA NPs. The proliferation of MKN-45 cells was then assessed by cell counting. The uptake of NPs was imaged by fluorescence microscopy and flow cytometry. The release of ibuprofen from ibuprofen-loaded PLGA NPs in the cells was evaluated by gas chromatography–mass spectrometry.Results: Dramatic inhibition of cellular proliferation was observed in cells treated with ibuprofen-loaded PLGA NPs versus those treated with free ibuprofen at the same concentration. The localization of NPs was cytoplasmic. The initiation of ibuprofen release was rapid, commencing within 2 hours, and then increased slowly over time, reaching a maximum

  10. Application of SeDeM expert systems in preformulation studies of pediatric ibuprofen ODT tablets.

    Science.gov (United States)

    Sipos, Emese; Oltean, Andrea Ramona; Szabó, Zoltán-István; Rédai, Emőke-Margit; Nagy, Gabriella Dónáth

    2017-06-27

    Pediatric, ibuprofen containing orodispersible tablets (ODTs) were prepared using the SeDeM expert system methodology. In order to facilitate formulation, directly compressible ibuprofen was employed (Ibuprofen DC 8TM) and characterized using its SeDeM profile. The mannitol based superdisintegrant Ludiflash® was characterized by the SeDeM-ODT expert system, which also allowed calculation of the optimal excipient concentration in order to obtain suitable tablet hardness and disintegration time. After adding a sweetener and a standard combination of lubricants, the optimized formulation was directly compressed into tablets and evaluated in terms of tablet hardness, friability, disintegration time and dissolution profile. The SeDeM method was applied to determine the amount of corrective excipient (Ludiflash®) required for the compression of Ibuprofen DC 85TM in order to achieve suitable ODTs. Adequate tablet hardness, disintegration time, friability and dissolution profiles were found during tablet evaluation.

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

    Science.gov (United States)

    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.

  12. The modifying effect of ibuprofen on total body irradiation-induced elevation of oxidative reactions in male hamsters

    International Nuclear Information System (INIS)

    Dokmeci, D.; Akpolat, M.; Aydogdu, N.; Uzal, C.; Turan, N.F.

    2004-01-01

    Radiation therapy plays an important role in curative and palliative treatments of malignant diseases. Because of the lipid component in the membrane, lipid peroxidation has been reported to be particularly susceptible to radiation damage. However, lipid peroxidation is reversed by cellular defense mechanisms, and the use of various antioxidants involved in these mechanisms have recently been suggested to be beneficial. It is known that ibuprofen has antioxidative and/or free radical scavenging activities. Our purpose is to examine the antioxidant capacity of ibuprofen in hamsters undergoing total body irradiation (TBI). Ibuprofen was given by gavage at dose of 10 mg/kg for 15 consecutive days. After this period, animals were exposed to TBI 60 Co gamma irradiation with a single dose of 8 Gy. After 24 h radiation exposure, the hamsters were killed and samples were taken from blood. Plasma thiobarbituric acid reactive substances (TBARS) increased significantly after radiation exposure, and ibuprofen diminished the amounts of TBARS. Significant protection of the radiation-induced changes in the activities of superoxide dismutase (SOD) and catalase was also recorded in the blood of ibuprofen-treated and -irradiated hamsters. These results suggest that ibuprofen with its antioxidant capacity could play a modulatory role against cellular damage effected by free radicals induced by TBI. (author)

  13. Adsorption of ibuprofen from aqueous solution on chemically surface-modified activated carbon cloths

    Directory of Open Access Journals (Sweden)

    Hanen Guedidi

    2017-05-01

    Full Text Available This study aims to investigate the performance of an activated carbon cloth for adsorption of ibuprofen. The cloth was oxidized by a NaOCl solution (0.13 mol L−1 or thermally treated under N2 (700 °C for 1 hour. The raw and modified cloths were characterized by N2 adsorption–desorption measurement at 77 K, CO2 adsorption at 273 K, Boehm titrations, pHPZC measurements, X-ray Photoelectron Spectroscopy analysis, and by infrared spectroscopy. The NaOCl treatment increases the acidic sites, mostly creating phenolic and carboxylic groups and decreases both the specific surface area and slightly the micropore volume. However, the thermal treatment at 700 °C under N2 induced a slight increase in the BET specific surface area and yielded to the only increase in the carbonyl group content. Ibuprofen adsorption studies of kinetics and isotherms were carried out at pH = 3 and 7. The adsorption properties were correlated to the cloth porous textures, surface chemistry and pH conditions. The isotherms of adsorption were better reproduced by Langmuir–Freundlich models at 298, 313 and 328 K. The adsorption of ibuprofen on the studied activated carbon cloths at pH 3 was an endothermic process. The pore size distributions of all studied ibuprofen-loaded fabrics were determined by DFT method to investigate the accessible porosity of the adsorbate. Both treatments do not influence the kind of micropores where the adsorption of ibuprofen occurred.

  14. Ibuprofen, paracetamol, and steam for patients with respiratory tract infections in primary care: pragmatic randomised factorial trial.

    Science.gov (United States)

    Little, Paul; Moore, Michael; Kelly, Joanne; Williamson, Ian; Leydon, Geraldine; McDermott, Lisa; Mullee, Mark; Stuart, Beth

    2013-10-25

    To assess strategies for advice on analgesia and steam inhalation for respiratory tract infections. Open pragmatic parallel group factorial randomised controlled trial. Primary care in United Kingdom. Patients aged ≥ 3 with acute respiratory tract infections. 889 patients were randomised with computer generated random numbers in pre-prepared sealed numbered envelopes to components of advice or comparator advice: advice on analgesia (take paracetamol, ibuprofen, or both), dosing of analgesia (take as required v regularly), and steam inhalation (no inhalation v steam inhalation). Primary: mean symptom severity on days 2-4; symptoms rated 0 (no problem) to 7 (as bad as it can be). Secondary: temperature, antibiotic use, reconsultations. Neither advice on dosing nor on steam inhalation was significantly associated with changes in outcomes. Compared with paracetamol, symptom severity was little different with ibuprofen (adjusted difference 0.04, 95% confidence interval -0.11 to 0.19) or the combination of ibuprofen and paracetamol (0.11, -0.04 to 0.26). There was no evidence for selective benefit with ibuprofen among most subgroups defined before analysis (presence of otalgia; previous duration of symptoms; temperature >37.5 °C; severe symptoms), but there was evidence of reduced symptoms severity benefit in the subgroup with chest infections (ibuprofen -0.40, -0.78 to -0.01; combination -0.47; -0.84 to -0.10), equivalent to almost one in two symptoms rated as a slight rather than a moderately bad problem. Children might also benefit from treatment with ibuprofen (ibuprofen: -0.47, -0.76 to -0.18; combination: -0.04, -0.31 to 0.23). Reconsultations with new/unresolved symptoms or complications were documented in 12% of those advised to take paracetamol, 20% of those advised to take ibuprofen (adjusted risk ratio 1.67, 1.12 to 2.38), and 17% of those advised to take the combination (1.49, 0.98 to 2.18). Mild thermal injury with steam was documented for four patients

  15. CLINICAL EFFICACY OF IBUPROFEN IN THERAPY FOR VIRAL UPPER RESPIRATORY TRACT INFECTIONS IN INFANTS

    Directory of Open Access Journals (Sweden)

    I.O. Skugarevskaya

    2006-01-01

    Full Text Available A study of use of ibuprofen in cases of viral upper respiratory tract infections (Vuri in children of early childhood has proved its' safety and efficacy. This medical agent has not only terminate fever but also diminished some other symptoms of Vuri.Key words: ibuprofen, viral upper respiratory tract infections, children.

  16. Development and optimization of the synthesis of new thiazolidin-4-one derivatives of ibuprofen.

    Science.gov (United States)

    Vasincu, Ioana; Apotrosoaei, Maria; Panzariu, Andreea; Buron, F; Routier, S; Profire, Lenuta

    2014-01-01

    Ibuprofen, an important nonsteroidal anti-inflammatory agent, is one of the most prescribed drugs for the treatment of pain and inflammation from various rheumatic diseases, but some side effects can occur on long-term use. The method for synthesis optimization of new derivatives of Ibuprofen with thiazolidin-4-one moiety, with improved pharmacological and toxicological profile. To optimize the derivatization method of free carboxyl group of Ibuprofen (2-(4-isobutylphenyl)propionic acid) the reaction conditions were varied (reagent ratio, catalyst, reaction medium). The most favorable method was proved to be the reaction between ibuprofen hydrazone and mercaptoacetic acid, in excess, at 80-85 degrees C, for 6 h with 96% conversion rate. The synthesis of 2-phenyl-3-[2-(4-(isobutyl)phenyl)-2-methyl]acetamido-thiazolidin-4-one derivative was optimized in view of applying it as a general procedure for the synthesis of other derivatives with related structure. The chemical structure and molecular weight of the synthesized compound were confirmed by spectral methods (IR, 1H NMR, 13C NMR, HR-MS).

  17. High-dose ibuprofen therapy associated with esophageal ulceration after pneumonectomy in a patient with cystic fibrosis: a case report

    Directory of Open Access Journals (Sweden)

    Anbar Ran D

    2004-09-01

    Full Text Available Abstract Background Lung disease in patients with cystic fibrosis is thought to develop as a result of airway inflammation, infection, and obstruction. Pulmonary therapies for cystic fibrosis that reduce airway inflammation include corticosteroids, rhDNase, antibiotics, and high-dose ibuprofen. Despite evidence that high-dose ibuprofen slows the progression of lung disease in patients with cystic fibrosis, many clinicians have chosen not to use this therapy because of concerns regarding potential side effects, especially gastrointestinal bleeding. However, studies have shown a low incidence of gastrointestinal ulceration and bleeding in patients with cystic fibrosis who have been treated with high-dose ibuprofen. Case presentation The described case illustrates a life-threatening upper gastrointestinal bleed that may have resulted from high-dose ibuprofen therapy in a patient with CF who had undergone a pneumonectomy. Mediastinal shift post-pneumonectomy distorted the patient's esophageal anatomy and may have caused decreased esophageal motility, which led to prolonged contact of the ibuprofen with the esophagus. The concentrated effect of the ibuprofen, as well as its systemic effects, probably contributed to the occurrence of the bleed in this patient. Conclusions This report demonstrates that gastrointestinal tract anatomical abnormalities or dysmotility may be contraindications for therapy with high-dose ibuprofen in patients with cystic fibrosis.

  18. Experimental substantiation of effectively administration of vinboron for analgesic activity increase of ibuprofen

    Directory of Open Access Journals (Sweden)

    F. V. Hladkykh

    2016-12-01

    Full Text Available Background. The increase of NSAIDs safety is current direction of modern pharmacology, because of so-called "class-specific" adverse reactions, which are common to this class, and the leading place among them is occupied by gastro-intestinal toxicity. In previous studies we have proved the ability of vinboron to neutralize ulcerogenic effect of ibuprofen (Hladkykh F.V. and al., 2014. The presence of the proven analgesic activity in the domestic antispasmodics (Stepaniuk H.I. and al., 2007 serves as the basis for research of vinboron action on analgesic aspect of ibuprofen pharmacotherapeutic effec. Aim is to conduct research in silico of the relation «molecular structure – anelgetic activity» of vinboron and to prove experimentally in vivo the practicability of vinboron using with the aim to increase the analgesic activity of ibuprofen on the model of adjuvant arthritis in rats. Materials and methods. The study of the relation «molecular structure – activity anelgetic» of vinboron was conducted in silico by PASS- analysis of biological activity spectrum. The analysis was set online with direct insertion of structural formula of vinboron in browser using Marvin JS web-resource «PASS Online» (http://www.way2drug.com/passonline. Analgesic activity in vivo was studied on the model of acute thermal pain, which was simulated in the conventional behavioral test of nociception «Hot plate». The lag of pain reaction was determined at the beginning («0» day, on 7, 14, 21 and 28 days of experiment. Results and discussion. According to the PASS-forecast the mechanisms of vinboron analgesic activity is caused by agonism towards the vanilloid (TRPV1 receptors (Pa=0,490; Pi=0,008, agonism to the μ (mu – receptor (Pa=0,323; Pi=0,036, inhibition of GABA (Pa=0,329; Pi=0,089 and others. Experimental studies have shown that the combined administration of ibuprofen and vinboron analgesic activity was higher than the results by ibuprofen monotherapy

  19. Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth

    NARCIS (Netherlands)

    Bailey, E.; Worthington, H.V.; van Wijk, A.; Yates, J.M.; Coulthard, P.; Afzal, Z.

    2013-01-01

    Background Both paracetamol and ibuprofen are commonly used analgesics for the relief of pain following the surgical removal of lower wisdom teeth (third molars). In 2010, a novel analgesic (marketed as Nuromol) containing both paracetamol and ibuprofen in the same tablet was launched in the United

  20. Application of SeDeM expert systems in preformulation studies of pediatric ibuprofen ODT tablets

    Directory of Open Access Journals (Sweden)

    Sipos Emese

    2017-06-01

    Full Text Available Pediatric, ibuprofen containing orodispersible tablets (ODTs were prepared using the SeDeM expert system methodology. In order to facilitate formulation, directly compressible ibuprofen was employed (Ibuprofen DC 8TM and characterized using its SeDeM profile. The mannitol based superdisintegrant Ludiflash® was characterized by the SeDeM-ODT expert system, which also allowed calculation of the optimal excipient concentration in order to obtain suitable tablet hardness and disintegration time. After adding a sweetener and a standard combination of lubricants, the optimized formulation was directly compressed into tablets and evaluated in terms of tablet hardness, friability, disintegration time and dissolution profile. The SeDeM method was applied to determine the amount of corrective excipient (Ludiflash® required for the compression of Ibuprofen DC 85TM in order to achieve suitable ODTs. Adequate tablet hardness, disintegration time, friability and dissolution profiles were found during tablet evaluation.

  1. NEW DATA ON THE SAFETY OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS: THE CONCEPT OF THE HIGH CLASS-SPECIFIC CARDIOVASCULAR RISK OF SELECTIVE CYCLOOXYGENASE-2 INHIBITORS IS OUTDATED

    Directory of Open Access Journals (Sweden)

    A. E. Karateev

    2017-01-01

    Full Text Available The results of the PRECISION trial were published in late 2016. During this trial, a total of 24,081 patients at high cardiovascular risk took celecoxib 200-400 mg/day, naproxen 750–1000 mg/day or ibuprofen 1800–2400 mg/day for more than 1.5 years (20.3±16.0 months. The findings show that the frequency of vascular catastrophes (death, nonfatal myocardial infarction, and stroke in patients receiving celecoxib was not higher than that of the similar complications in those taking the control drugs. At the same time, celecoxib demonstrated a statistically significant advantage in reducing the risk of serious gastrointestinal complications. New evidence refutes the concept of high cardiovascular risk that is common to all coxibs and confirms the provisions of national guidelines for the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs, which were published in 2015. This review presents recent data on the risk of NSAID-related complications, including a brief description of the design and results of the PRECISION trial. 

  2. Effect of ibuprofen on menstrual blood prostaglandin levels in dysmenorrheic women.

    Science.gov (United States)

    Pulkkinen, M O; Csapo, A I

    1979-07-01

    In a randomized crossover study 15 dysmenorrheic women were treated during two consecutive menstrual period, once with the potent prostaglandin-synthesis inhibitor: ibuprofen and once with an identical looking placebo. Each patient was medicated for 12 hours during the first day of her menstrual flow and was subsequently fitted with a cervical cup for the collection of menstrual blood during three hours. In these samples the concentrations of prostaglandin (PG)F and PGE were measured by radioimmunoassay. The patients receiving placebo had high PGF levels 135 +/- 27 ng/ml (Mean +/- S.E.) which were significnatly reduced by Ibuprofen to 24 +/- 5 ng/ml (P less than 0.001). The PGE concentrations decreased from 5 +/- 1 ng/ml to 2 +/- 1 ng/ml (P less than 0.05). Ibuprofen also reduced the menstrual pain significantly (P less than 0.001). These results substantiate the earlier conclusion that a causal relationship exists between effective treatment with PG-synthesis inhibitors and decrease in menstrual blood PG levels, intrauterine pressure and dysmenorrheic pain.

  3. Non-Steroidal Anti-Inflammatory Drug Use and the Risk of Acute Myocardial Infarction in the General German Population: A Nested Case-Control Study.

    Science.gov (United States)

    Thöne, Kathrin; Kollhorst, Bianca; Schink, Tania

    2017-09-01

    Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with an increased relative risk of acute myocardial infarction (AMI), but the label warnings refer particularly to patients with cardiovascular risk factors. The magnitude of relative AMI risk for patients with and without cardiovascular risk factors varies between studies depending on the drugs and doses studied. The aim of our study was to estimate population-based relative AMI risks for individual and widely used NSAIDs, for a cumulative amount of NSAID use, and for patients with and without a prior history of cardiovascular risk factors. Based on data from the German Pharmacoepidemiological Research Database (GePaRD) of about 17 million insurance members from four statutory health insurance providers, for the years 2004-2009, a nested case-control study was conducted within a cohort of 3,476,931 new NSAID users classified into current, recent, or past users. Up to 100 controls were matched to each case by age, sex, and length of follow-up using risk set sampling. Multivariable conditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Duration of NSAID use was calculated by the cumulative amount of dispensed defined daily doses (DDDs), and stratified analyses were conducted for potential effect modifiers. Overall, 17,236 AMI cases were matched to 1,714,006 controls. Elevated relative AMI risks were seen for current users of fixed combinations of diclofenac with misoprostol (OR 1.76, 95% CI 1.26-2.45), indometacin (1.69, 1.22-2.35), ibuprofen (1.54, 1.43-1.65), etoricoxib (1.52, 1.24-1.87), and diclofenac (1.43, 1.34-1.52) compared with past use. A low cumulative NSAID amount was associated with a higher relative AMI risk for ibuprofen, diclofenac, and indometacin. The relative risk associated with current use of diclofenac, fixed combinations of diclofenac with misoprostol, etoricoxib, and ibuprofen was highest in the younger age group

  4. Effects of Addition of Preoperative Intravenous Ibuprofen to Pregabalin on Postoperative Pain in Posterior Lumbar Interbody Fusion Surgery

    Directory of Open Access Journals (Sweden)

    Hüseyin Ulaş Pınar

    2017-01-01

    Full Text Available Objective. Ibuprofen and pregabalin both have independent positive effects on postoperative pain. The aim of the study is researching effect of 800 mg i.v. ibuprofen in addition to preoperative single dose pregabalin on postoperative analgesia and morphine consumption in posterior lumbar interbody fusion surgery. Materials and Methods. 42 adult ASA I-II physical status patients received 150 mg oral pregabalin 1 hour before surgery. Patients received either 250 ml saline with 800 mg i.v. ibuprofen or saline without ibuprofen 30 minutes prior to the surgery. Postoperative analgesia was obtained by morphine patient controlled analgesia (PCA and 1 g i.v. paracetamol every six hours. PCA morphine consumption was recorded and postoperative pain was evaluated by Visual Analog Scale (VAS in postoperative recovery room, at the 1st, 2nd, 4th, 8th, 12th, 24th, 36th, and 48th hours. Results. Postoperative pain was significantly lower in ibuprofen group in recovery room, at the 1st, 2nd, 36th, and 48th hours. Total morphine consumption was lower in ibuprofen group at the 2nd, 4th, 8th, 12th, and 48th hours. Conclusions. Multimodal analgesia with preoperative ibuprofen added to preoperative pregabalin safely decreases postoperative pain and total morphine consumption in patients having posterior lumbar interbody fusion surgery, without increasing incidences of bleeding or other side effects.

  5. Determination of etoricoxib in human plasma using automated on-line solid-phase extraction coupled with LC-APCI/MS/MS

    Directory of Open Access Journals (Sweden)

    Sérgio Luiz Dalmora

    2008-01-01

    Full Text Available A liquid chromatography-tandem mass spectrometry method with atmospheric pressure chemical ionization (LC-APCI/MS/MS was validated for the determination of etoricoxib in human plasma using antipyrin as internal standard, followed by on-line solid-phase extraction. The method was performed on a Luna C18 column and the mobile phase consisted of acetonitrile:water (95:5, v/v/ammonium acetate (pH 4.0; 10 mM, run at a flow rate of 0.6 mL/min. The method was linear in the range of 1-5000 ng/mL (r²>0.99. The lower limit of quantitation was 1 ng/mL. The recoveries were within 93.72-96.18%. Moreover, method validation demonstrated acceptable results for the precision, accuracy and stability studies.

  6. Accelerating the design of molecularly imprinted nanocomposite membranes modified by Au@polyaniline for selective enrichment and separation of ibuprofen

    Science.gov (United States)

    Wu, Xiuling; Wu, Yilin; Dong, Hongjun; Zhao, Juan; Wang, Chen; Zhou, Shi; Lu, Jian; Yan, Yongsheng; Li, He

    2018-01-01

    A novel system for harvesting molecularly imprinted nanocomposite membranes (MINcMs) with Au-modified polyaniline (Au@polyaniline) nanocomposite structure was developed for selective enrichment and separation of ibuprofen. This unique nanocomposite structure obviously enhanced the adsorption capacity, perm-selectivity performance, and regeneration ability of MINcMs. The as-prepared MINcMs showed outstanding adsorption capacity (22.02 mg g-1) of ibuprofen, which was four times higher than that of non-imprinted nanocomposite membranes (NINcMs). Furthermore, the selectivity factor of MINcMs for ibuprofen reached up to 4.67 and the perm-selectivity factor β was about 8.74, which indicated MINcMs had a good selective separation performance of ibuprofen. We envision that this novel synthesis method will open a new direction to manipulation of molecularly imprinted membrane materials and provide a simple yet convenient way to selective separation of ibuprofen.

  7. Application of non-thermal plasma reactor and Fenton reaction for degradation of ibuprofen

    Energy Technology Data Exchange (ETDEWEB)

    Marković, Marijana [Center of Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 12-16, 11000 Belgrade (Serbia); Jović, Milica; Stanković, Dalibor [Innovation Center, Faculty of Chemistry, University of Belgrade, P.O. Box 51, 11058 Belgrade 118 (Serbia); Kovačević, Vesna [Faculty of Physics, University of Belgrade, P.O. Box 44, 11000 Belgrade (Serbia); Roglić, Goran [Faculty of Chemistry, University of Belgrade, P.O. Box 51, 11058 Belgrade 118 (Serbia); Gojgić-Cvijović, Gordana [Center of Chemistry, Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 12-16, 11000 Belgrade (Serbia); Manojlović, Dragan, E-mail: manojlo@chem.bg.ac.rs [Faculty of Chemistry, University of Belgrade, P.O. Box 51, 11058 Belgrade 118 (Serbia)

    2015-02-01

    Pharmaceutical compounds have been detected frequently in surface and ground water. Advanced Oxidation Processes (AOPs) were reported as very efficient for removal of various organic compounds. Nevertheless, due to incomplete degradation, toxic intermediates can induce more severe effects than the parent compound. Therefore, toxicity studies are necessary for the evaluation of possible uses of AOPs. In this study the effectiveness and capacity for environmental application of three different AOPs were estimated. They were applied and evaluated for removal of ibuprofen from water solutions. Therefore, two treatments were performed in a non-thermal plasma reactor with dielectric barrier discharge with and without a homogenous catalyst (Fe{sup 2+}). The third treatment was the Fenton reaction. The degradation rate of ibuprofen was measured by HPLC-DAD and the main degradation products were identified using LC–MS TOF. Twelve degradation products were identified, and there were differences according to the various treatments applied. Toxicity effects were determined with two bioassays: Vibrio fischeri and Artemia salina. The efficiency of AOPs was demonstrated for all treatments, where after 15 min degradation percentage was over 80% accompanied by opening of the aromatic ring. In the treatment with homogenous catalyst degradation reached 99%. V. fischeri toxicity test has shown greater sensitivity to ibuprofen solution after the Fenton treatment in comparison to A. salina. - Highlights: • Twelve ibuprofen degradation products were identified in total. • The degradation percentage differed between treatments (DBD/Fe{sup 2+} was 99%). • In DBD/Fe{sup 2+} only aliphatic degradation products were identified. • V. fischeri was sensitive to ibuprofen solution after the Fenton treatment. • A. salina showed no toxic effect when exposed to all post treatment solutions.

  8. Application of non-thermal plasma reactor and Fenton reaction for degradation of ibuprofen

    International Nuclear Information System (INIS)

    Marković, Marijana; Jović, Milica; Stanković, Dalibor; Kovačević, Vesna; Roglić, Goran; Gojgić-Cvijović, Gordana; Manojlović, Dragan

    2015-01-01

    Pharmaceutical compounds have been detected frequently in surface and ground water. Advanced Oxidation Processes (AOPs) were reported as very efficient for removal of various organic compounds. Nevertheless, due to incomplete degradation, toxic intermediates can induce more severe effects than the parent compound. Therefore, toxicity studies are necessary for the evaluation of possible uses of AOPs. In this study the effectiveness and capacity for environmental application of three different AOPs were estimated. They were applied and evaluated for removal of ibuprofen from water solutions. Therefore, two treatments were performed in a non-thermal plasma reactor with dielectric barrier discharge with and without a homogenous catalyst (Fe 2+ ). The third treatment was the Fenton reaction. The degradation rate of ibuprofen was measured by HPLC-DAD and the main degradation products were identified using LC–MS TOF. Twelve degradation products were identified, and there were differences according to the various treatments applied. Toxicity effects were determined with two bioassays: Vibrio fischeri and Artemia salina. The efficiency of AOPs was demonstrated for all treatments, where after 15 min degradation percentage was over 80% accompanied by opening of the aromatic ring. In the treatment with homogenous catalyst degradation reached 99%. V. fischeri toxicity test has shown greater sensitivity to ibuprofen solution after the Fenton treatment in comparison to A. salina. - Highlights: • Twelve ibuprofen degradation products were identified in total. • The degradation percentage differed between treatments (DBD/Fe 2+ was 99%). • In DBD/Fe 2+ only aliphatic degradation products were identified. • V. fischeri was sensitive to ibuprofen solution after the Fenton treatment. • A. salina showed no toxic effect when exposed to all post treatment solutions

  9. Use of ibuprofen sustained release for treating osteoarthritic pain: findings from 15 general medical practices in Egypt

    Directory of Open Access Journals (Sweden)

    Khalifa N

    2014-05-01

    Full Text Available Nabil Khalifa,1 Timour El-Husseini,1 Ahmed Morrah,2 Elshenawy Mostafa,3 Hesham Hamoud41Department of Orthopedic Surgery, Ain Shams University, Cairo, Egypt; 2Department of Orthopedic Surgery, Cairo University, Cairo, Egypt; 3Department of Orthopedic Surgery, Mansoura University, Mansoura, Egypt; 4Department of Rheumatology, Azhar University, Cairo, EgyptPurpose: Ibuprofen sustained release (SR has been shown to provide effective symptomatic pain relief in chronic arthritic conditions such as osteoarthritis in European and US patient populations. Few studies have been conducted in other patient populations. A 4-week prospective multicenter open-label observational study was designed to explore and describe the combined effect of ibuprofen SR and standard medical care in patients suffering from osteoarthritis in 15 general medical practices in Egypt.Patients and methods: In total, 519 patients were prescribed ibuprofen SR 2 ×800 mg once daily for 4 weeks.Results: Ibuprofen SR combined with standard medical care significantly improved day and night pain, with 99.4% of the patients reporting improvement. The treatment reduced the symptom severity of joint tenderness/stiffness and the duration of morning stiffness, and allowed more patients to carry out normal activities. Overall compliance with the prescribed ibuprofen SR regimen was 98.6%. Ibuprofen SR was generally well tolerated with no serious adverse events reported during the study. There was no increase in blood pressure or heart rate.Conclusion: The combined treatment provided effective relief of pain in patients with osteoarthritis in a large real-life general medical practice setting in Egypt. Owing to its convenient once-daily dosing regimen, ibuprofen SR may enhance patient compliance.Keywords: chronic arthritis, compliance, pain score, real-life

  10. Oral morphine versus ibuprofen administered at home for postoperative orthopedic pain in children: a randomized controlled trial.

    Science.gov (United States)

    Poonai, Naveen; Datoo, Natasha; Ali, Samina; Cashin, Megan; Drendel, Amy L; Zhu, Rongbo; Lepore, Natasha; Greff, Michael; Rieder, Michael; Bartley, Debra

    2017-10-10

    Oral morphine for postoperative pain after minor pediatric surgery, while increasingly popular, is not supported by evidence. We evaluated whether oral morphine was superior to ibuprofen for at-home management of children's postoperative pain. We conducted a randomized superiority trial comparing oral morphine (0.5 mg/kg) with ibuprofen (10 mg/kg) in children 5 to 17 years of age who had undergone minor outpatient orthopedic surgery (June 2013 to September 2016). Participants took up to 8 doses of the intervention drug every 6 hours as needed for pain at home. The primary outcome was pain, according to the Faces Pain Scale - Revised, for the first dose. Secondary outcomes included additional analgesic requirements, adverse effects, unplanned health care visits and pain scores for doses 2 to 8. We analyzed data for 77 participants in each of the morphine and ibuprofen groups. Both interventions decreased pain scores with no difference in efficacy. The median difference in pain score before and after the first dose of medication was 1 (interquartile range 0-1) for both morphine and ibuprofen ( p = 0.2). For doses 2 to 8, the median differences in pain score before and after the dose were not significantly different between groups. Significantly more participants taking morphine reported adverse effects (45/65 [69%] v. 26/67 [39%], p ibuprofen groups, respectively; p = 0.003). Morphine was not superior to ibuprofen, and both drugs decreased pain with no apparent difference in efficacy. Morphine was associated with significantly more adverse effects, which suggests that ibuprofen is a better first-line option after minor surgery. ClinicalTrials.gov, no. NCT01686802. © 2017 Canadian Medical Association or its licensors.

  11. Celecoxib-Induced Self-Assembly of Smart Albumin-Doxorubicin Conjugate for Enhanced Cancer Therapy.

    Science.gov (United States)

    Shi, Leilei; Xu, Li; Wu, Chenwei; Xue, Bai; Jin, Xin; Yang, Jiapei; Zhu, Xinyuan

    2018-03-14

    Recent years have witnessed the great contributions that drug combination therapy has made for enhanced cancer therapy. However, because of the complicated pharmacokinetics of combined drug formulations, the majority of combination strategies show severe adverse effects at high dosage and poor biodistribution in vivo. To overcome these deficiencies and achieve enhanced cancer therapy, we put forward a method to construct a smart albumin-based nanoplatform, denoted as K237-HSA-DC, for codelivery of cyclooxygenase-2 (COX-2) inhibitor (celecoxib) and chemotherapeutic agent (doxorubicin, DOX). Both in vitro and in vivo studies indicate that K237-HSA-DC exhibits the best therapeutic efficacy on tumor cells compared with all the other formulations. Moreover, K237-HSA-DC shows fewer side effects on normal organs in contrast to other formulations. To understand the reasons behind the improved drug efficacy in depth, we performed a cell metabonomics-based mechanism study and found that celecoxib could enhance the inhibitory effect of DOX on the transport of glucose into cells and then lead to subsequent significant energy metabolism inhibition. Considering the above-mentioned advantages of K237-HSA-DC, we believe the smart albumin-based nanoplatform can serve as a promising drug delivery system for enhanced cancer therapy.

  12. A double-blind study comparing ibuprofen 1800 mg or 2400 mg daily and placebo in sports injuries.

    Science.gov (United States)

    Hutson, M A

    1986-01-01

    In a double-blind, placebo-controlled study of forty-six patients with acute ligamentous damage of the knee, ibuprofen in dosages 1800 mg and 2400 mg produced significant improvements in joint mobility, weight bearing ability and match fitness. Joint effusion, pain on stress and pain severity was significantly improved by all three treatments. Only two patients reported side-effects (one while taking placebo and one taking ibuprofen 2400 mg). The study confirmed the efficacy and excellent tolerance to ibuprofen in patients with sports injuries to the knee.

  13. Contribution of microorganisms to non-extractable residue formation during biodegradation of ibuprofen in soil

    Energy Technology Data Exchange (ETDEWEB)

    Nowak, Karolina M., E-mail: karolina.nowak@ufz.de [UFZ, Helmholtz Centre for Environmental Research, Department of Environmental Biotechnology, Permoserstraße 15, 04318 Leipzig (Germany); Department of Environmental Biology and Chemodynamics, Institute for Environmental Research (Biology V), RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Girardi, Cristobal; Miltner, Anja [UFZ, Helmholtz Centre for Environmental Research, Department of Environmental Biotechnology, Permoserstraße 15, 04318 Leipzig (Germany); Gehre, Matthias [UFZ, Helmholtz Centre for Environmental Research, Department of Isotope Biogeochemistry, Permoserstraße 15, 04318 Leipzig (Germany); Schäffer, Andreas [Department of Environmental Biology and Chemodynamics, Institute for Environmental Research (Biology V), RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Kästner, Matthias [UFZ, Helmholtz Centre for Environmental Research, Department of Environmental Biotechnology, Permoserstraße 15, 04318 Leipzig (Germany)

    2013-02-15

    Non-extractable residues (NER) formed during biodegradation of organic contaminants in soil are considered to be mainly composed of parent compounds or their primary metabolites with hazardous potential. However, in the case of biodegradable organic compounds, the soil NER may also contain microbial biomass components, for example fatty acids (FA) and amino acids (AA). After cell death, these biomolecules are subsequently incorporated into non-living soil organic matter (SOM) and are stabilised ultimately forming hardly extractable residues of biogenic origin. We investigated biodegradation of {sup 13}C{sub 6}-ibuprofen, in particular the metabolic incorporation of the {sup 13}C-label into FA and AA and their fate in soil over 90 days. {sup 13}C-FA and {sup 13}C-AA amounts in the living microbial biomass fraction initially increased, then decreased over time and were continuously incorporated into the non-living SOM pool. The {sup 13}C-FA in the non-living SOM remained stable from day 59 whereas the contents of {sup 13}C-AA slightly increased until the end. After 90 days, nearly all NER were biogenic as they were made up almost completely by natural biomass compounds. The presented data demonstrated that the potential environmental risks related to the ibuprofen-derived NER are overestimated. - Highlights: ► Biogenic residue formation during microbial degradation of ibuprofen was studied. ► Nearly all non-extractable residues derived from ibuprofen were biogenic. ► Fatty acids and amino acids formed biogenic non-extractable residues and were stabilised in soil. ► Environmental risks of ibuprofen-derived non-extractable residues are overestimated.

  14. Contribution of microorganisms to non-extractable residue formation during biodegradation of ibuprofen in soil

    International Nuclear Information System (INIS)

    Nowak, Karolina M.; Girardi, Cristobal; Miltner, Anja; Gehre, Matthias; Schäffer, Andreas; Kästner, Matthias

    2013-01-01

    Non-extractable residues (NER) formed during biodegradation of organic contaminants in soil are considered to be mainly composed of parent compounds or their primary metabolites with hazardous potential. However, in the case of biodegradable organic compounds, the soil NER may also contain microbial biomass components, for example fatty acids (FA) and amino acids (AA). After cell death, these biomolecules are subsequently incorporated into non-living soil organic matter (SOM) and are stabilised ultimately forming hardly extractable residues of biogenic origin. We investigated biodegradation of 13 C 6 -ibuprofen, in particular the metabolic incorporation of the 13 C-label into FA and AA and their fate in soil over 90 days. 13 C-FA and 13 C-AA amounts in the living microbial biomass fraction initially increased, then decreased over time and were continuously incorporated into the non-living SOM pool. The 13 C-FA in the non-living SOM remained stable from day 59 whereas the contents of 13 C-AA slightly increased until the end. After 90 days, nearly all NER were biogenic as they were made up almost completely by natural biomass compounds. The presented data demonstrated that the potential environmental risks related to the ibuprofen-derived NER are overestimated. - Highlights: ► Biogenic residue formation during microbial degradation of ibuprofen was studied. ► Nearly all non-extractable residues derived from ibuprofen were biogenic. ► Fatty acids and amino acids formed biogenic non-extractable residues and were stabilised in soil. ► Environmental risks of ibuprofen-derived non-extractable residues are overestimated

  15. Aldosterone glucuronidation inhibition as a potential mechanism for arterial dysfunction associated with chronic celecoxib and diclofenac use in patients with rheumatoid arthritis.

    Science.gov (United States)

    Crilly, Michael A; Mangoni, Arduino A; Knights, Kathleen M

    2013-01-01

    Adverse cardiovascular (CV) effects of non-steroidal anti-inflammatory drugs (NSAIDs) are largely independent of their cyclooxygenase (COX) enzyme selectivity, but could be a consequence of aldosterone 18ß-glucuronidation inhibition (AGI), which varies between NSAIDS. This study assesses the chronic effects of celecoxib (selective COX-2 inhibitor) versus diclofenac (non-selective NSAID) therapy on arterial dysfunction in patients with rheumatoid arthritis (RA). AGI was assessed in vitro using human kidney cortical microsomes. Arterial function was measured clinically as the extent (augmentation index, AIX%) and timing (reflected wave transit time, RWTT, msec) of arterial wave reflection using radial applanation pulse wave analysis (SphygmoCor PWA device) in 39 RA patients without overt CV disease aged 40-65. A higher AIX% (and lower RWTT) indicates arterial dysfunction. Clinical assessment on a single occasion included a fasting blood sample, patient questionnaire and medical record review. Multivariable analysis was used to adjust for sex, mean blood pressure, arthritis duration, cumulative ESR-years and current DMARD therapy. The inhibition constant (Ki) for celecoxib was lower than that of diclofenac (Ki, 3.5 vs. 8.4 μM). Chronic celecoxib use was associated with a higher AIX% (34.8 vs. 32.3) and lower RWTT (130.1 vs. 132.7 msec) compared with diclofenac. Adjusted mean differences were AIX% 4.7 (95%CI 0.6 to 8.9; p=0.03) and RWTT -3.6 (95%CI -10.0 to 2.7; p=0.26). Celecoxib has a greater potency for AGI than diclofenac and its use is associated with a significantly higher AIX%. Our findings support AGI as a plausible mechanism for the CV toxicity of NSAIDs.

  16. IL-1β Suppresses the Formation of Osteoclasts by Increasing OPG Production via an Autocrine Mechanism Involving Celecoxib-Related Prostaglandins in Chondrocytes

    Directory of Open Access Journals (Sweden)

    Yusuke Watanabe

    2009-01-01

    Full Text Available Elevated interleukin (IL-1 concentrations in synovial fluid have been implicated in joint bone and cartilage destruction. Previously, we showed that IL-1β stimulated the expression of prostaglandin (PG receptor EP4 via increased PGE2 production. However, the effect of IL-1β on osteoclast formation via chondrocytes is unclear. Therefore, we examined the effect of IL-1β and/or celecoxib on the expression of macrophage colony-stimulating factor (M-CSF, receptor activator of NF-κB ligand (RANKL, and osteoprotegerin (OPG in human chondrocytes, and the indirect effect of IL-1β on osteoclast-like cell formation using RAW264.7 cells. OPG and RANKL expression increased with IL-1β; whereas M-CSF expression decreased. Celecoxib blocked the stimulatory effect of IL-1β. Conditioned medium from IL-1β-treated chondrocytes decreased TRAP staining in RAW264.7 cells. These results suggest that IL-1β suppresses the formation of osteoclast-like cells via increased OPG production and decreased M-CSF production in chondrocytes, and OPG production may increase through an autocrine mechanism involving celecoxib-related PGs.

  17. Comparison of oral paracetamol versus ibuprofen in premature infants with patent ductus arteriosus: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Dan Dang

    Full Text Available TRIAL DESIGN: Oral ibuprofen has demonstrated good effects on symptomatic patent ductus arteriosus (PDA but with many contraindications and potential side-effects. In the past two years, oral paracetamol administration to several preterm infants with PDA has been reported. Here, a randomized, non-blinded, parallel-controlled and non-inferiority trial was designed to evaluate the efficacy and safety profiles of oral paracetamol to those of standard ibuprofen for PDA closure in premature infants. METHODS: One hundred and sixty infants (gestational age ≤ 34 weeks with echocardiographically confirmed PDA were randomly assigned to receive either oral paracetamol (n = 80 or ibuprofen (n = 80. After the initial treatment course in both groups, the need for a second course was determined by echocardiographic evaluation. The main outcome was rate of ductal closure, and secondary outcomes were adverse effects and complications. RESULT: The ductus was closed in 65 (81.2% infants of the paracetamol group compared with 63 (78.8% of the ibuprofen group. The 95% confidence interval of the difference between these groups was [-0.080,0.128], demonstrating that the effectiveness of paracetamol treatment was not inferior to that of ibuprofen. In fact, the incidence of hyperbilirubinemia or gastrointestinal bleeding in the paracetamol group was significantly lower than that of the ibuprofen group. No significant differences in other clinical side effects or complications were noted. CONCLUSION: This comparison of drug efficacy and safety profiles in premature infants with PDA revealed that oral paracetamol was comparable to ibuprofen in terms of the rate of ductal closure and even showed a decreased risk of hyperbilirubinemia or gastrointestinal bleeding. Therefore, paracetamol may be accepted as a first-line drug treatment for PDA in preterm infants. TRIAL REGISTRATION: ChiCTR.org ChiCTR-TRC-12002177.

  18. Comparison of oral and intravenous Ibuprofen for medical closure of patent ductus arteriosus: which one is better?

    Science.gov (United States)

    Olukman, Ozgur; Calkavur, Sebnem; Ercan, Gulten; Atlihan, Fusun; Oner, Taliha; Tavli, Vedide; Kultursay, Nilgun

    2012-01-01

    Intravenous ibuprofen is an expensive drug that is being used currently for treating and preventing patent ductus arteriosus. Although oral ibuprofen is much cheaper, there is limited data published about its safety and efficacy. The aim of this study was to compare two forms of ibuprofen in terms of safety and efficacy in closure of patent ductus arteriosus. This is a single-center retrospective study. Data were collected from patients' files of preterm infants who were hospitalized at the Neonatal Intensive Care Unit of Dr. Behcet Uz Children's Hospital between April 2009 and June 2010. Six hundred sixty infants were evaluated by echocardiography between 24 and 48 postnatal hours. Clinically and hemodynamically significant ductus arteriosus was defined in 66 infants with gestational age less than 32 weeks and birth weight less than 1500 g. Oral or intravenous ibuprofen (loading dose: 10 mg/kg on day 1, followed by maintenance dose: 5 mg/kg on days 2 and 3) was administered. Treatment success was defined as a completely closed duct without reopening on follow-up. Drug-associated renal, gastrointestinal, cerebral, hematological, and metabolic side effects were monitored and compared between treatment groups. Ductal closure rates were 100% and 97.6%, respectively, in the oral and intravenous groups. Hypernatremia was the remarkable side effect in the intravenous group, whereas bronchopulmonary dysplasia and septicemia were prominent in the oral group. No statistically significant difference could be demonstrated between the groups in terms of mortality rates. Oral ibuprofen therapy is as efficacious as intravenous ibuprofen with some concerns about increased sepsis and bronchopulmonary dysplasia incidence. However, comprehensive and large-scale pharmacokinetic studies are required in order to prove this efficacy. On the other hand, intravenous ibuprofen still remains to be the drug of choice for patent ductus arteriosus but only with meticulous control of serum

  19. Analgesic Efficacy of a New Immediate-Release/Extended-Release Formulation of Ibuprofen: Results From Single- and Multiple-Dose Postsurgical Dental Pain Studies.

    Science.gov (United States)

    Christensen, Steven; Paluch, Ed; Jayawardena, Shyamalie; Daniels, Stephen; Meeves, Suzanne

    2017-05-01

    Analgesic effects of ibuprofen immediate-release/extended-release (IR/ER) 600-mg tablets were evaluated in 2 randomized, double-blind, placebo-controlled dental pain studies. Patients 16-40 years old with moderate-severe pain following third-molar extraction received single-dose ibuprofen 600 mg IR/ER (formulation A or B), naproxen sodium 220 mg, or placebo (2:2:2:1; study 1) or 4 doses of ibuprofen 600 mg IR/ER (formulation A) or placebo (1:1; study 2). In study 1 (n = 196), mean (standard deviation [SD]) time-weighted sum of pain intensity difference scores for placebo, ibuprofen IR/ER A, ibuprofen IR/ER B, and naproxen, respectively, were 0.05 (9.2), 16.87 (9.4), 17.34 (10.5), and 12.66 (10.0) over 0-12 hours and -0.03 (4.1), 6.57 (4.4), 7.14 (5.2), and 5.14 (5.0) over 8-12 hours (all P ibuprofen IR/ER, respectively (P ibuprofen. Gastrointestinal adverse events predominated with placebo both after study medication administration and after rescue medication use, if applicable. Ibuprofen 600 mg IR/ER provided safe and effective analgesia after single and multiple doses. © 2016, The American College of Clinical Pharmacology.

  20. Ibuprofen versus mecillinam for uncomplicated cystitis - a randomized controlled trial study protocol

    DEFF Research Database (Denmark)

    Vik, Ingvild; Bollestad, Marianne; Grude, Nils

    2014-01-01

    , controlled, double blind trial following the principles of Good Clinical Practice. Women between the ages of 18 to 60 presenting with symptoms of uncomplicated cystitis are screened for eligibility. 500 women from four sites in Norway, Sweden and Denmark are allocated to treatment with 600 mg ibuprofen three.......DiscussionIf treatment of uncomplicated cystitis with ibuprofen is as effective as mecillinam for symptom relief, we can potentially reduce the use of antibiotics on a global scale.Trial registrationEudraCTnr: 2012-002776-14. ClinicalTrials.gov: NCT01849926....

  1. Cellular and molecular studies of the effects of a selective COX-2 inhibitor celecoxib in the cardiac cell line H9c2 and their correlation with death mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Sakane, K.K. [Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, São José dos Campos, SP (Brazil); Monteiro, C.J.; Silva, W.; Silva, A.R. [Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG (Brazil); Santos, P.M. [Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraíba, São José dos Campos, SP (Brazil); Lima, K.F. [Núcleo de Pesquisa em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG (Brazil); Moraes, K.C.M. [Instituto de Biociências, Departamento de Biologia, Universidade Estadual Paulista ‘‘Júlio de Mesquita Filho’’, Rio Claro, SP (Brazil)

    2013-11-29

    Cardiovascular disease is one of the leading causes of death worldwide, and evidence indicates a correlation between the inflammatory process and cardiac dysfunction. Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme are not recommended for long-term use because of potentially severe side effects to the heart. Considering this and the frequent prescribing of commercial celecoxib, the present study analyzed cellular and molecular effects of 1 and 10 µM celecoxib in a cell culture model. After a 24-h incubation, celecoxib reduced cell viability in a dose-dependent manner as also demonstrated in MTT assays. Furthermore, reverse transcription-polymerase chain reaction analysis showed that the drug modulated the expression level of genes related to death pathways, and Western blot analyses demonstrated a modulatory effect of the drug on COX-2 protein levels in cardiac cells. In addition, the results demonstrated a downregulation of prostaglandin E2 production by the cardiac cells incubated with celecoxib, in a dose-specific manner. These results are consistent with the decrease in cell viability and the presence of necrotic processes shown by Fourier transform infrared analysis, suggesting a direct correlation of prostanoids in cellular homeostasis and survival.

  2. 75 FR 48352 - Determination That MOTRIN (Ibuprofen) Tablets and Four Other Drug Products Were Not Withdrawn...

    Science.gov (United States)

    2010-08-10

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0391] Determination That MOTRIN (Ibuprofen) Tablets and Four Other Drug Products Were Not Withdrawn From Sale for... Applicant NDA 17-463 MOTRIN (ibuprofen) Tablets, 300 milligrams (mg), McNeil Consumer Healthcare, 7050 Camp...

  3. Quantitative analysis of ibuprofen in pharmaceuticals and human control serum using kinetic spectrophotometry

    Directory of Open Access Journals (Sweden)

    SNEZANA S. MITIC

    2008-08-01

    Full Text Available The aim of this work was to develop a new kinetic spectrophoto-metric method for the determination of ibuprofen in pharmaceutical for-mulations. Ibuprofen was determined in an acidic ethanolic medium by monitoring the rate of appearance of 1-nitroso-2-naphthol, resulting from the displacement by ibuprofen of Co(III from the tris(1-nitroso-2-naptholatocobalt(III complex. The optimum operating conditions regarding reagent concentrations and temperature were established. The tangent method was adopted for constructing the calibration curve, which was found to be linear over the concentration range 0.21–1.44 and 1.44–2.06 µg ml-1. The optimized conditions yielded a theoretical detection limit of 0.03 µg ml-1 based on the 3.3 S0 criterion. The interference effects of the usual excipients of powdery drugs, foreign ions and amino acids on the reaction rate were studied in order to assess the selectivity of the method. The developed procedure was successfully applied for the rapid determination of ibuprofen in commercial pharmaceutical formulations and human control serum. The unique features of this procedure are that the determination can be performed at room temperature and the analysis time is short. The newly developed method is simple, inexpensive and efficient for use in the analysis of a large number of samples.

  4. Intravenous ibuprofen: the first injectable product for the treatment of pain and fever

    Directory of Open Access Journals (Sweden)

    P Brandon Bookstaver

    2010-05-01

    Full Text Available P Brandon Bookstaver, April D Miller, Celeste N Rudisill, LeAnn B NorrisDepartment of Clinical Pharmacy and Outcomes Sciences, South Carolina College of Pharmacy, University of South Carolina Campus, Columbia, South Carolina, USAAbstract: This paper reviews the current data on the use of the first approved intravenous ibuprofen product for the management of post-operative pain and fever in the United States. The management of acute and post-operative pain and fever with nonsteroidal anti-inflammatory agents (NSAIDs is well documented. A search in Medline and International Pharmaceutical Abstracts of articles until the end of November 2009 and references of all citations were conducted. Available manufacturer data on file were also analyzed for this report. Several randomized controlled studies have demonstrated the opioid-sparing and analgesic effects of 400 and 800 mg doses of intravenous ibuprofen in a series of post-operative patient populations. Two recent studies have also noted the improvement in fever curves in critically ill and burn patients. These data, along with pharmacokinetic and pharmacologic properties, are explored in this review, which addresses the clinical utility of a parenteral NSAID in a hospitalized patient for post-operative pain management and fever reduction. Further data on intravenous ibuprofen are needed to define long-term utilization, management of acute pain, and use in special populations.Keywords: ibuprofen, intravenous, injectable, nonsteroidal anti-inflammatory drug

  5. Prophylactic Acetaminophen or Ibuprofen Results in Equivalent Acute Mountain Sickness Incidence at High Altitude: A Prospective Randomized Trial.

    Science.gov (United States)

    Kanaan, Nicholas C; Peterson, Alicia L; Pun, Matiram; Holck, Peter S; Starling, Jennifer; Basyal, Bikash; Freeman, Thomas F; Gehner, Jessica R; Keyes, Linda; Levin, Dana R; O'Leary, Catherine J; Stuart, Katherine E; Thapa, Ghan B; Tiwari, Aditya; Velgersdyk, Jared L; Zafren, Ken; Basnyat, Buddha

    2017-06-01

    Recent trials have demonstrated the usefulness of ibuprofen in the prevention of acute mountain sickness (AMS), yet the proposed anti-inflammatory mechanism remains unconfirmed. Acetaminophen and ibuprofen were tested for AMS prevention. We hypothesized that a greater clinical effect would be seen from ibuprofen due to its anti-inflammatory effects compared with acetaminophen's mechanism of possible symptom reduction by predominantly mediating nociception in the brain. A double-blind, randomized trial was conducted testing acetaminophen vs ibuprofen for the prevention of AMS. A total of 332 non-Nepali participants were recruited at Pheriche (4371 m) and Dingboche (4410 m) on the Everest Base Camp trek. The participants were randomized to either acetaminophen 1000 mg or ibuprofen 600 mg 3 times a day until they reached Lobuche (4940 m), where they were reassessed. The primary outcome was AMS incidence measured by the Lake Louise Questionnaire score. Data from 225 participants who met inclusion criteria were analyzed. Twenty-five participants (22.1%) in the acetaminophen group and 18 (16.1%) in the ibuprofen group developed AMS (P = .235). The combined AMS incidence was 19.1% (43 participants), 14 percentage points lower than the expected AMS incidence of untreated trekkers in prior studies at this location, suggesting that both interventions reduced the incidence of AMS. We found little evidence of any difference between acetaminophen and ibuprofen groups in AMS incidence. This suggests that AMS prevention may be multifactorial, affected by anti-inflammatory inhibition of the arachidonic-acid pathway as well as other analgesic mechanisms that mediate nociception. Additional study is needed. Copyright © 2017 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

  6. Celecoxib Enhances the Efficacy of Low-Dose Antibiotic Treatment against Polymicrobial Sepsis in Mice and Clinical Isolates of ESKAPE Pathogens.

    Science.gov (United States)

    Annamanedi, Madhavi; Varma, Gajapati Y N; Anuradha, K; Kalle, Arunasree M

    2017-01-01

    Treatment of multidrug resistant bacterial infections has been a great challenge globally. Previous studies including our study have highlighted the use of celecoxib, a non-steroidal anti-inflammatory drug in combination with antibiotic has decreased the minimal inhibitory concentration to limit Staphylococcus aureus infection. However, the efficacy of this combinatorial treatment against various pathogenic bacteria is not determined. Therefore, we have evaluated the potential use of celecoxib in combination with low doses of antibiotic in limiting Gram-positive and Gram-negative bacteria in vivo in murine polymicrobial sepsis developed by cecum ligation and puncture (CLP) method and against clinically isolated human ESKAPE pathogens ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and Enterobacter species). The in vivo results clearly demonstrated a significant reduction in the bacterial load in different organs and in the inflammatory markers such as COX-2 and NF-κB via activation of SIRT1 in mice treated with imipenem, a choice of antibiotic for polymicrobial sepsis treatment. Combinatorial treatment of ampicillin and celecoxib was effective on clinical isolates of ESKAPE pathogens, 45% of tested clinical isolates showed more than 50% reduction in the colony forming units when compared to ampicillin alone. In conclusion, this non-traditional treatment strategy might be effective in clinic to reduce the dose of antibiotic to treat drug-resistant bacterial infections.

  7. Crystal engineering of ibuprofen compounds: From molecule to crystal structure to morphology prediction by computational simulation and experimental study

    Science.gov (United States)

    Zhang, Min; Liang, Zuozhong; Wu, Fei; Chen, Jian-Feng; Xue, Chunyu; Zhao, Hong

    2017-06-01

    We selected the crystal structures of ibuprofen with seven common space groups (Cc, P21/c, P212121, P21, Pbca, Pna21, and Pbcn), which was generated from ibuprofen molecule by molecular simulation. The predicted crystal structures of ibuprofen with space group P21/c has the lowest total energy and the largest density, which is nearly indistinguishable with experimental result. In addition, the XRD patterns for predicted crystal structure are highly consistent with recrystallization from solvent of ibuprofen. That indicates that the simulation can accurately predict the crystal structure of ibuprofen from the molecule. Furthermore, based on this crystal structure, we predicted the crystal habit in vacuum using the attachment energy (AE) method and considered solvent effects in a systematic way using the modified attachment energy (MAE) model. The simulation can accurately construct a complete process from molecule to crystal structure to morphology prediction. Experimentally, we observed crystal morphologies in four different polarity solvents compounds (ethanol, acetonitrile, ethyl acetate, and toluene). We found that the aspect ratio decreases of crystal habits in this ibuprofen system were found to vary with increasing solvent relative polarity. Besides, the modified crystal morphologies are in good agreement with the observed experimental morphologies. Finally, this work may guide computer-aided design of the desirable crystal morphology.

  8. Celecoxib decreases growth and angiogenesis and promotes apoptosis in a tumor cell line resistant to chemotherapy

    Directory of Open Access Journals (Sweden)

    Carlos Rosas

    2014-01-01

    Full Text Available BACKGROUND: During the last few years it has been shown in several laboratories that Celecoxib (Cx, a non-steroidal anti-inflammatory agent (NSAID normally used for pain and arthritis, mediates antitumor and antiangiogenic effects. However, the effects of this drug on a tumor cell line resistant to chemotherapeutical drugs used in cancer have not been described. Herein we evaluate the angiogenic and antitumor effects of Cx in the development of a drug-resistant mammary adenocarcinoma tumor (TA3-MTXR. RESULTS: Cx reduces angiogenesis in the chick embryonic chorioallantoic membrane assay (CAM, inhibits the growth and microvascular density of the murine TA3-MTXR tumor, reduces microvascular density of tumor metastases, promotes apoptosis and reduces vascular endothelial growth factor (VEGF production and cell proliferation in the tumor. CONCLUSION: The antiangiogenic and antitumor Cx effects correlate with its activity on other tumor cell lines, suggesting that Prostaglandins (PGs and VEGF production are involved. These results open the possibility of using Celecoxib combined with other experimental therapies, ideally aiming to get synergic effects.

  9. Effectiveness and safety of celecoxib combined with diacerein in the treatment of senile degenerative knee osteoarthritis: study protocol and preliminary results of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Guo-dong Wang

    2017-01-01

    Full Text Available Background and objectives: The non-steroidal anti-inflammatory drug celecoxib, used for the treatment of senile degenerative knee osteoarthritis, has a rapid onset of action and few side effects. However, it cannot prevent the occurrence and development of knee osteoarthritis. Celecoxib withdrawal is likely to induce a rebound increase in inflammation that may aggravate symptoms. Diacerein is a drug used to improve articular cartilage metabolism. It can delay the progression of senile degenerative knee osteoarthritis, but has a slow onset of action. Whether combined treatment with celecoxib and diacerein provides complimentary actions to achieve a better therapeutic effect on senile degenerative knee osteoarthritis remains unclear. >Design: A prospective, single-center, randomized controlled trial. Methods: Three hundred patients with senile degenerative knee osteoarthritis who receive treatment at the Department of Orthopedics, Second Affiliated Hospital of Nanjing Medical University, China will be randomly assigned to the celecoxib (200 mg, once a day, orally, diacerein (50 mg, twice a day, orally, and celecoxib + diacerein (celecoxib 200 mg, once a day, orally and diacerein 50 mg, twice a day, orally groups, with 100 patients in each group. Patients in each group will be treated for 12 successive weeks, and a 36-week follow-up will be performed. At 24 weeks after treatment, the VAS score for pain during the 20-meter walk test and osteoarthritis index were significantly decreased in the diacerein and celecoxib + diacerein groups compared to pre-treatment (P Outcome measures and preliminary results: The primary outcome measure of this study is the Visual Analogue Scale (VAS score for pain during the 20-meter walk test before and 1, 4, 12, 24, and 36 weeks after treatment. The secondary outcome measures of this study include osteoarthritis index and X-ray image findings of the knee before and 1, 4, 12, 24, and 36 weeks after treatment, as well

  10. Agglomeration of Celecoxib by Quasi Emulsion Solvent Diffusion Method: Effect of Stabilizer

    Directory of Open Access Journals (Sweden)

    Maryam Maghsoodi

    2016-12-01

    Full Text Available Purpose: The quasi-emulsion solvent diffusion (QESD has evolved into an effective technique to manufacture agglomerates of API crystals. Although, the proposed technique showed benefits, such as cost effectiveness, that is considerably sensitive to the choice of a stabilizer, which agonizes from a absence of systemic understanding in this field. In the present study, the combination of different solvents and stabilizers were compared to investigate any connections between the solvents and stabilizers. Methods: Agglomerates of celecoxib were prepared by QESD method using four different stabilizers (Tween 80, HPMC, PVP and SLS and three different solvents (methyl acetate, ethyl acetate and isopropyl acetate. The solid state of obtained particles was investigated by differential scanning calorimetry (DSC and Fourier transform infrared (FT-IR spectroscopy. The agglomerated were also evaluated in term of production yield, distribution of particles and dissolution behavior. Results: The results showed that the effectiveness of stabilizer in terms of particle size and particle size distribution is specific to each solvent candidate. A stabilizer with a lower HLB value is preferred which actually increased its effectiveness with the solvent candidates with higher lipophilicity. HPMC appeared to be the most versatile stabilizer because it showed a better stabilizing effect compared to other stabilizers in all solvents used. Conclusion: This study demonstrated that the efficiency of stabilizers in forming the celecoxib agglomerates by QESD was influenced by the HLB of the stabilizer and lipophilicity of the solvents.

  11. Dynamic plantwide modeling, uncertainty and sensitivity analysis of a pharmaceutical upstream synthesis: Ibuprofen case study

    DEFF Research Database (Denmark)

    Montes, Frederico C. C.; Gernaey, Krist; Sin, Gürkan

    2018-01-01

    A dynamic plantwide model was developed for the synthesis of the Active pharmaceutical Ingredient (API) ibuprofen, following the Hoescht synthesis process. The kinetic parameters, reagents, products and by-products of the different reactions were adapted from literature, and the different process...... operations integrated until the end process, crystallization and isolation of the ibuprofen crystals. The dynamic model simulations were validated against available measurements from literature and then used as enabling tool to analyze the robustness of design space. To this end, sensitivity of the design...... space towards input disturbances and process uncertainties (from physical and model parameters) is studied using Monte Carlo simulations. The results quantify the uncertainty of the quality of product attributes, with particular focus on crystal size distribution and ibuprofen crystalized. The ranking...

  12. Comparison of analgesic efficacy of flupirtine maleate and ibuprofen in gynaecological ambulatory surgeries: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Vanita Ahuja

    2015-01-01

    Full Text Available Background and Aims: Flupirtine maleate is a centrally acting, non-opioid analgesic with unique muscle relaxant properties as compared to common analgesics. The aim of this study was to compare post-operative analgesic efficacy of flupirtine maleate and ibuprofen in patients undergoing gynaecological ambulatory surgeries. Methods: This prospective, randomised controlled study was conducted in 60 women of American Society of Anesthesiologists physical status I/II, 18-70 years of age and scheduled to undergo gynaecological ambulatory surgeries. The participants were randomised to receive either 100 mg oral flupirtine maleate (group flupirtine, n = 30 or 800 mg oral ibuprofen (group ibuprofen, n = 30, 1 h prior to surgery and then every 8 h for 48 h. Verbal Numerical Rating Scale (VNRS on movement was assessed at 0, 2, 4, 6 and 8 h following surgery. Following discharge from hospital, the patients were interviewed telephonically at 12, 24 and 48 h post-operatively. VNRS was statistically analysed using Mann-Whitney test. Results: VNRS on movement was statistically reduced at 2 h after surgery (P = 0.04 in group flupirtine as compared to group ibuprofen. The analgesic efficacy was similar in both the groups at 4, 6, 8, 12, 24 and 48 h after surgery. The satisfaction scores at 24 and 48 h post-operatively were superior in group flupirtine as compared to group ibuprofen (P < 0.001. Conclusion: Analgesic efficacy of flupirtine maleate was comparable with ibuprofen in patients in ambulatory gynaecological patients up to 48 h postoperatively with superior satisfaction scores.

  13. Maternal use of acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy and risk of cryptorchidism

    DEFF Research Database (Denmark)

    Jensen, Morten Søndergaard; Rebordosa, Cristina; Thulstrup, Ane Marie

    2010-01-01

    Cyclooxygenase (COX) inhibitors-acetaminophen, ibuprofen and acetylsalicylic acid-have endocrine-disruptive properties in the rainbow trout. In humans, aspirin blocks the androgen response to human chorionic gonadotropin (hCG), and, because hCG-stimulated androgen production in utero is crucial...... for normal testicular descent, exposure to COX inhibitors at vulnerable times during gestation may impair testicular descent. We examined whether prenatal exposure to acetaminophen, ibuprofen, and acetylsalicylic acid was associated with increased occurrence of cryptorchidism....

  14. Celecoxib prevents colitis associated colon carcinogenesis: an upregulation of apoptosis.

    Science.gov (United States)

    Setia, Shruti; Nehru, Bimla; Sanyal, Sankar N

    2014-12-01

    Uncontrolled cell proliferation and suppressed apoptosis are the critical events transforming a normal cell to a cancerous one wherein the inflammatory microenvironment supports this oncogenic transformation. The process of colon carcinogenesis may be aggravated in chronic inflammatory conditions such as ulcerative colitis where non-steroidal anti-inflammatory drugs (NSAIDs) may effectively prevent the cellular and molecular events. Western blots and immunofluorescent analysis of DNA mismatch repair enzymes, cell cycle regulators and pro- and anti-apoptotic proteins were performed in dextran sulfate sodium (DSS)-induced ulcerative colitis and 1,2-dimethyl benz(a)anthracene (DMH)-induced colon cancer. Also, apoptotic studies were done in isolated colonocytes using fluorescent staining and in paraffin sections using TUNEL assay. An upregulation of cell cycle regulators: cyclin D1/cdk4 and cyclin E/cdk2 and anti-apoptotic Bcl-2, along with the suppression of DNA repair enzymes: MLH1 and MSH2; tumour suppressors: p53, p21and Rb and pro-apoptotic proteins: Bax and Bad were observed in the DSS, DMH and DSS+DMH groups. Proliferating cell nuclear antigen (PCNA) was also overexpressed in these groups. The ultimate executioner of the apoptotic pathway; caspase-3, was suppressed in these groups. Apoptotic studies in colonocytes and paraffin sections revealed suppressed apoptosis in these groups. These effects were corrected with the administration of a second generation NSAID, celecoxib along with the treatment of DSS and DMH. The chemopreventive action of celecoxib in colitis mediated colon carcinogenesis may include the regulation of DNA mismatch repair enzymes, cell cycle check points, cell proliferation and apoptosis. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  15. Development and evaluation of ibuprofen transdermal gel formulations

    African Journals Online (AJOL)

    A commercial ibuprofen gel product (Ibutop®) was used as a reference. Results: The formulations containing 5 % of either menthol or glycerol as permeation enhancers gave drug release patterns comparable to that of the reference product. Propanol increased the apparent viscosity of the test gels to the same extent as that ...

  16. Jejunal perforation by swallowed ibuprofen caplet | Njoku | Nigerian ...

    African Journals Online (AJOL)

    We present a case of jejunal perforation caused by an unusual foreign body, an ibuprofen caplet in its blister packing believed to be the first of its kind, perforation of the intestine caused by an ingested medication. The patient eventually developed an enterocutaneous fistula through the weak wall of a preexisting incisional ...

  17. Synthesis of Ibuprofen in the Introductory Organic Laboratory

    Science.gov (United States)

    Kjonaas, Richard A.; Williams, Peggy E.; Counce, David A.; Crawley, Lindsey R.

    2011-01-01

    A method for the synthesis of ibuprofen in introductory organic chemistry laboratory courses is reported. This experiment requires two 3-h lab sessions. All of the reactions and techniques are a standard part of any introductory organic chemistry course. In the first lab session, students reduce p-isobutylacetophenone to an alcohol and then…

  18. Comparison of the effect of ibuprofen and slow-released Diclofenac Sodium in controlling post endodontic pain

    Directory of Open Access Journals (Sweden)

    Saatchi M

    2010-01-01

    Full Text Available "nBackground and Aims: Despite the significant improvement in dentistry, pain after endodontic therapy is still of concern for patients. Non-steroidal anti-inflammatory drugs are the most commonly prescribed oral analgesics used for dental pain relief after root canal treatment. The purpose of this study was to compare the effectiveness of Ibuprofen versus slow-released Diclofenac Sodium in controlling pain following root canal treatment. "nMaterials and Methods: In this randomized clinical trial, mandibular molars with irreversible pulpitis in 90 patients were selected. The patients were divided into three groups (Ibuprofen, slow-released Diclofenac Sodium and placebo. After examination patients filled in the consent form. Then they received one of the mentioned drugs. After inferior alveolar nerve block, access cavity was prepared and the root canals were prepared using passive step back method. The canals were dried and temporary filling material was placed. Then the pain evaluation form (visual analog scale was explained and delivered to the patients. Data were analyzed using Repeated Measurement ANOVA, Kruskal-wallis and Man-Whitney U tests. "nResults: The mean pain intensity in slow-released Diclofenac Sodium group was 0.87 0.95, 1.17 1.10 for Ibuprofen group, and 2.14  1.70 for placebo group. The differences between groups were statistically significant (P<0.001. The effect of Ibuprofen in controlling post endodontic pain in the first 2 hours was more than slow-released Diclofenac Sodium (P=0.01, but in 10, 18, and 36 hours after treatment, slow-released Diclofenac Sodium was more effective than Ibuprofen (P<0.001. "nConclusion: Premedication with single dose of slow-released Diclofenac Sodium can control post endodontic pain for a longer period of time compared with Ibuprofen. "n.

  19. A clinical trial comparing Lanconone® with ibuprofen for rapid relief in acute joint pain.

    Science.gov (United States)

    Girandola, Robert N; Srivastava, Shalini; Loullis, Costas C

    2016-04-06

    To study the effect of Lanconone® (1000 mg) on acute pain on exertion as compared to the standard of care, Ibuprofen (400 mg). The study recruited 72 subjects diagnosed with mild to moderate knee joint pain on exertion. Subjects with Pain Visual Analogue Scale of more than 40 mm were included. Uphill walking was provided as the stressor using Naughton's protocol on a treadmill. The subjects walked for 10 minutes continuously followed by a rest period and baseline pain score for index knee joint was recorded. Subjects were administered a single dose of Lanconone® (1000 mg)/Ibuprofen (400 mg). Thereafter the same stressor was provided at 0.5, 1, 2, 3, 4, and 6 hours, subsequently, pain scores were recorded on a visual analogue scale. Double stopwatch method was used to evaluate the onset of pain relief and time taken to meaningful pain relief. Both Lanconone® and Ibuprofen showed the first perceived pain relief at 65.31 ± 35.57 mins as compared to 60.82 ± 32.56 mins respectively. The mean time taken to experience meaningful pain relief in Lanconone® group was 196.59 ± 70.85 mins compared to 167.13 ± 71.41 mins amongst Ibuprofen group. The meaningful pain relief continued for 6 hours. The current study successfully demonstrated rapid pain-relieving potential of Lanconone® which was comparable to Ibuprofen. No adverse event related to the interventions was reported in the study. Clinical trials.gov NCT02417506 . 21 January 2015.

  20. Vapour-phase method in the synthesis of polymer-ibuprofen sodium-silica gel composites.

    Science.gov (United States)

    Kierys, Agnieszka; Krasucka, Patrycja; Grochowicz, Marta

    2017-11-01

    The study discusses the synthesis of polymer-silica composites comprising water soluble drug (ibuprofen sodium, IBS). The polymers selected for this study were poly(TRIM) and poly(HEMA- co -TRIM) produced in the form of permanently porous beads via the suspension-emulsion polymerization method. The acid and base set ternary composites were prepared by the saturation of the solid dispersions of drug (poly(TRIM)-IBS and/or poly(HEMA- co -TRIM)-IBS) with TEOS, and followed by their exposition to the vapour mixture of water and ammonia, or water and hydrochloric acid, at autogenous pressure. The conducted analyses reveal that the internal structure and total porosity of the resulting composites strongly depend on the catalyst which was used for silica precursor gelation. The parameters characterizing the porosity of both of the acid set composites are much lower than the parameters of the base set composites. Moreover, the basic catalyst supplied in the vapour phase does not affect the ibuprofen sodium molecules, whereas the acid one causes transformation of the ibuprofen sodium into the sodium chloride and a derivative of propanoic acid, which is poorly water soluble. The release profiles of ibuprofen sodium from composites demonstrate that there are differences in the rate and efficiency of drug desorption from them. They are mainly affected by the chemical character of the polymeric carrier but are also associated with the restricted swelling of the composites in the buffer solution after precipitation of silica gel.

  1. Vapour-phase method in the synthesis of polymer-ibuprofen sodium-silica gel composites

    Directory of Open Access Journals (Sweden)

    Agnieszka Kierys

    2017-11-01

    Full Text Available The study discusses the synthesis of polymer-silica composites comprising water soluble drug (ibuprofen sodium, IBS. The polymers selected for this study were poly(TRIM and poly(HEMA-co-TRIM produced in the form of permanently porous beads via the suspension-emulsion polymerization method. The acid and base set ternary composites were prepared by the saturation of the solid dispersions of drug (poly(TRIM-IBS and/or poly(HEMA-co-TRIM-IBS with TEOS, and followed by their exposition to the vapour mixture of water and ammonia, or water and hydrochloric acid, at autogenous pressure. The conducted analyses reveal that the internal structure and total porosity of the resulting composites strongly depend on the catalyst which was used for silica precursor gelation. The parameters characterizing the porosity of both of the acid set composites are much lower than the parameters of the base set composites. Moreover, the basic catalyst supplied in the vapour phase does not affect the ibuprofen sodium molecules, whereas the acid one causes transformation of the ibuprofen sodium into the sodium chloride and a derivative of propanoic acid, which is poorly water soluble. The release profiles of ibuprofen sodium from composites demonstrate that there are differences in the rate and efficiency of drug desorption from them. They are mainly affected by the chemical character of the polymeric carrier but are also associated with the restricted swelling of the composites in the buffer solution after precipitation of silica gel.

  2. Controlled release of ibuprofen by meso-macroporous silica

    Science.gov (United States)

    Santamaría, E.; Maestro, A.; Porras, M.; Gutiérrez, J. M.; González, C.

    2014-02-01

    Structured meso-macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (EO19PO39EO19) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption-desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso-macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system.

  3. Ibuprofen loaded PLA nanofibrous scaffolds increase proliferation of human skin cells in vitro and promote healing of full thickness incision wounds in vivo.

    Science.gov (United States)

    Mohiti-Asli, M; Saha, S; Murphy, S V; Gracz, H; Pourdeyhimi, B; Atala, A; Loboa, E G

    2017-02-01

    This article presents successful incorporation of ibuprofen in polylactic acid (PLA) nanofibers to create scaffolds for the treatment of both acute and chronic wounds. Nanofibrous PLA scaffolds containing 10, 20, or 30 wt % ibuprofen were created and ibuprofen release profiles quantified. In vitro cytotoxicity to human epidermal keratinocytes (HEK) and human dermal fibroblasts (HDF) of the three scaffolds with varying ibuprofen concentrations were evaluated and compared to pure PLA nanofibrous scaffolds. Thereafter, scaffolds loaded with ibuprofen at the concentration that promoted human skin cell viability and proliferation (20 wt %) were evaluated in vivo in nude mice using a full thickness skin incision model to determine the ability of these scaffolds to promote skin regeneration and/or assist with scarless healing. Both acellular and HEK and HDF cell-seeded 20 wt % ibuprofen loaded nanofibrous bandages reduced wound contraction compared with wounds treated with Tegaderm™ and sterile gauze. Newly regenerated skin on wounds treated with cell-seeded 20 wt % ibuprofen bandages exhibited significantly greater blood vessel formation relative to acellular ibuprofen bandages. We have found that degradable anti-inflammatory scaffolds containing 20 wt % ibuprofen promote human skin cell viability and proliferation in vitro, reduce wound contraction in vivo, and when seeded with skin cells, also enhance new blood vessel formation. The approaches and results reported here hold promise for multiple skin tissue engineering and wound healing applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 327-339, 2017. © 2015 Wiley Periodicals, Inc.

  4. The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol

    OpenAIRE

    Tanner, Trevor; Aspley, Sue; Munn, Andrew; Thomas, Tracy

    2010-01-01

    Background Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet. Methods Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-...

  5. Silver-functionalized carbon nanofiber composite electrodes for ibuprofen detection

    NARCIS (Netherlands)

    Manea, F.; Motoc, S.; Pop, A.; Remes, A.; Schoonman, J.

    2012-01-01

    The aim of this study is to prepare and characterize two types of silver-functionalized carbon nanofiber (CNF) composite electrodes, i.e., silver-decorated CNF-epoxy and silver-modified natural zeolite-CNF-epoxy composite electrodes suitable for ibuprofen detection in aqueous solution. Ag carbon

  6. Design and evaluation of mucoadhesive microemulsion for neuroprotective effect of ibuprofen following intranasal route in the MPTP mice model.

    Science.gov (United States)

    Mandal, Surjyanarayan; Mandal, Snigdha Das; Chuttani, Krishna; Sawant, Krutika K; Subudhi, Bharat Bhushan

    2016-08-01

    The present study is to investigate the neuroprotective effect of ibuprofen by intranasal administration of mucoadhesive microemulsion (MMEI) against inflammation-mediated by dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD). Ibuprofen-loaded polycarbophil-based MMEI was developed by using response surface methodology (RSM). Ibuprofen with dose of 2.86 mg/kg/day was administered intranasally to male C57BL/6 mice for two consecutive weeks which were pre-treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals. Immunohistochemistry was performed. Optimal MMEI was stable and non-ciliotoxic with 66.29 ± 4.15 nm as average globule size and -20.9 ± 3.98 mV as zeta potential. PDI value and transmission electron microscopy result showed the narrow globule size distribution of MMEI. The result showed that all three independent variables had a significant effect (p open-field test findings revealed the significant improvement in motor performance and gross behavioral activity of the mice. The results from in vivo study and immunohistochemistry showed that nasal administration of Ibuprofen significantly reduced the MPTP-mediated dopamine depletion. Furthermore TH neurons count in the substantia nigra and the density of striatal dopaminergic nerve terminals were found to be significant higher for ibuprofen treated groups. Findings of the investigation revealed that Ibuprofen through developed MMEI was shown to protect neurons against MPTP-induced injury in the Substantia nigra pars compacta (SNpc) and striatum and hence, could be a promising approach for brain targeting of Ibuprofen through intranasal route to treat PD.

  7. Synthesis and characterization of thermosensitive hydrogels and the investigation of modified release of ibuprofen

    Directory of Open Access Journals (Sweden)

    Ilić-Stojanović Snežana S.

    2013-01-01

    Full Text Available The method of the synthesis of poly(N-isopropylacrylamide-co-2-hydroxypropyl methacrylate hydrogels obtained by radical polymerization is described. Their characterization was carried out by the determination of the quantity of residual monomers and by investigating their structure using the FTIR. Three glass transitions were detected by DSC method. The porous surfaces of hydrogels with incorporated ibuprofen were shown in SEM micrographs. The swelling ratio of hydrogels decreased with the temperature increase and the swelling transport mechanism was changed from non-Fickian to Fickian. Ibuprofen was incorporated in hydrogel as a drug carrier and released quantity was monitored by HPLC method depending on the temperature. Hydrogel with the lower cross-linker content had the highest swelling degree (α = 34.72 at 10°C and released the largest amount of ibuprofen (64.21 mg/gxerogel at 40°C. [Projekat Ministarstva nauke Republike Srbije, br. TR-34012

  8. Thin-coating as an alternative approach to improve flow properties of ibuprofen powder

    DEFF Research Database (Denmark)

    Genina, Natalja; Räikkönen, Heikki; Ehlers, Henrik

    2010-01-01

    In the present study, thin-coating as a potential method for improving flow properties of cohesive ibuprofen powder was introduced. Briefly, the technique was based on the successive deposition of ultrasound-assisted fine polymer mist onto the surface of the powdered active pharmaceutical...... ingredient (API), producing individual particles with a hydrophilic thin-coat. A 0.15% m/V aqueous solution of hydroxypropyl methylcellulose (HPMC) was used. Particle size and surface analysis revealed a decrease in the cohesiveness of ibuprofen powder and an increase in the homogeneity of particle surfaces...

  9. Comparison of the clinical efficacy of methylprednisolone with ibuprofen and ibuprofen alone on the postoperative sequelae of surgical removal of impacted third molar

    Directory of Open Access Journals (Sweden)

    Navneet Kaur

    2014-01-01

    Full Text Available Purpose: The aim of the study was to compare the clinical efficacy of methylprednisolone with ibuprofen to ibuprofen alone on the postoperative sequelae of surgical removal of impacted third molars. Materials and Methods: The present study was conducted on the 35 patients requiring surgical extraction of bilateral impacted third molars attending the Outpatient Department of Oral and Maxillofacial Surgery, Guru Nanak Dev Dental College and Research Institute. The impacted teeth were removed in two sessions at least 3 weeks apart. The selected patients were randomly put on regimen 1 or regimen II at either the first or second surgery in accordance with randomization plan. The measurements and recordings for pain, swelling, and interincisal distance (mouth opening, were made on 1 st , 3 rd , and 7 th day postoperatively on the scales designed for the purpose. The data recorded was compiled and put to statistical analysis. Results: It was observed from the present study that postoperative sequelae, that is, pain, swelling, and trismus was significantly less in the regimen I group than regimen II group on the 1 st and 3 rd postoperative day. Conclusion: The results of this study substantiate the fact that a single class of drugs (nonsteroidal anti-inflammatory drug (NSAID is less effective in controlling postoperative inflammatory sequelae than the combination of ibuprofen (NSAID and methylprednisolone (corticosteroid following the third molar surgery. Therefore, this pharmaceutical combination should be considered for attenuation of postoperative sequelae in healthy patients undergoing surgical removal of impacted mandibular third molar.

  10. Multiple binding modes of ibuprofen in human serum albumin identified by absolute binding free energy calculations

    KAUST Repository

    Evoli, Stefania

    2016-11-10

    Human serum albumin possesses multiple binding sites and transports a wide range of ligands that include the anti-inflammatory drug ibuprofen. A complete map of the binding sites of ibuprofen in albumin is difficult to obtain in traditional experiments, because of the structural adaptability of this protein in accommodating small ligands. In this work, we provide a set of predictions covering the geometry, affinity of binding and protonation state for the pharmaceutically most active form (S-isomer) of ibuprofen to albumin, by using absolute binding free energy calculations in combination with classical molecular dynamics (MD) simulations and molecular docking. The most favorable binding modes correctly reproduce several experimentally identified binding locations, which include the two Sudlow\\'s drug sites (DS2 and DS1) and the fatty acid binding sites 6 and 2 (FA6 and FA2). Previously unknown details of the binding conformations were revealed for some of them, and formerly undetected binding modes were found in other protein sites. The calculated binding affinities exhibit trends which seem to agree with the available experimental data, and drastically degrade when the ligand is modeled in a protonated (neutral) state, indicating that ibuprofen associates with albumin preferentially in its charged form. These findings provide a detailed description of the binding of ibuprofen, help to explain a wide range of results reported in the literature in the last decades, and demonstrate the possibility of using simulation methods to predict ligand binding to albumin.

  11. Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT.

    Science.gov (United States)

    Sawitzke, Allen D; Shi, Helen; Finco, Martha F; Dunlop, Dorothy D; Harris, Crystal L; Singer, Nora G; Bradley, John D; Silver, David; Jackson, Christopher G; Lane, Nancy E; Oddis, Chester V; Wolfe, Fred; Lisse, Jeffrey; Furst, Daniel E; Bingham, Clifton O; Reda, Domenic J; Moskowitz, Roland W; Williams, H James; Clegg, Daniel O

    2010-08-01

    Knee osteoarthritis (OA) is a major cause of pain and functional limitation in older adults, yet longer-term studies of medical treatment of OA are limited. To evaluate the efficacy and safety of glucosamine and chondroitin sulphate (CS), alone or in combination, as well as celecoxib and placebo on painful knee OA over 2 years. A 24-month, double-blind, placebo-controlled study, conducted at nine sites in the US ancillary to the Glucosamine/chondroitin Arthritis Intervention Trial, enrolled 662 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence grade 2 or 3 changes and baseline joint space width of at least 2 mm). This subset continued to receive their randomised treatment: glucosamine 500 mg three times daily, CS 400 mg three times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The primary outcome was a 20% reduction in Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain over 24 months. Secondary outcomes included an Outcome Measures in Rheumatology/Osteoarthritis Research Society International response and change from baseline in WOMAC pain and function. Compared with placebo, the odds of achieving a 20% reduction in WOMAC pain were celecoxib: 1.21, glucosamine: 1.16, combination glucosamine/CS: 0.83 and CS alone: 0.69, and were not statistically significant. Over 2 years, no treatment achieved a clinically important difference in WOMAC pain or function as compared with placebo. However, glucosamine and celecoxib showed beneficial but not significant trends. Adverse reactions were similar among treatment groups and serious adverse events were rare for all treatments.

  12. The Role of Prophylactic Ibuprofen and N-Acetylcysteine on the Level of Cytokines in Periapical Exudates and the Post-Treatment Pain

    Directory of Open Access Journals (Sweden)

    Seyyed Mohsen Aghajanpour Mir

    2012-09-01

    Full Text Available Background Periapical lesions are inflammatory diseases that result in periapical bone destruction because of host defensive-microbial disturbances. Objective:To evaluate the role of prophylactic ibuprofen and N-acetylcysteine (NAC on the levels of tumor necrosis factor alpha (TNF- alpha, interleukin- 6(IL-6 and IL-17 and post-treatment pain level in chronic periapical lesions. Materials and methods Eighty patients with chronic apical lesions less than 1 cm were randomly assigned to receive NAC tablets (400 mg, ibuprofen tablets (400 mg, NAC (400 mg/ibuprofen (200 mg combination and placebo 90 minutes prior to sampling. Periapical exudates were collected from root canals. TNF- alpha, IL-6 and IL-17 levels were determined by ELISA and posttreatment pain was assessed using a visual analog scale (VAS. Results:There was a significant difference in IL-6 level between ibuprofen group and placebo (p = 0.019. Significant difference in IL-17 level was observed between NAC/ibuprofen combination group and placebo (p = 0.043. Four hours after treatment, a significant difference was observed in VAS pain score between ibuprofen group and placebo (p = 0.017. Eight hours post-treatment, VAS pain score for NAC group was statistically lower than placebo group (p = 0.033. After 12 hours VAS pain score showed a significant decrease in NAC group compared to placebo (p = 0.049. Conclusion:The prophylactic ibuprofen and NAC failed to clearly reflect their effect on cytokines levels in exudates of chronic periapical lesions. On the other hand it seems that NAC can be a substitute for ibuprofen in the management of post endodontic pain

  13. The role of prophylactic ibuprofen and N-acetylcysteine on the level of cytokines in periapical exudates and the post-treatment pain

    Directory of Open Access Journals (Sweden)

    Ehsani Maryam

    2012-09-01

    Full Text Available Abstract Background Periapical lesions are inflammatory diseases that result in periapical bone destruction because of host defensive–microbial disturbances. Objective To evaluate the role of prophylactic ibuprofen and N-acetylcysteine (NAC on the levels of tumor necrosis factor alpha (TNF- α, interleukin- 6(IL-6 and IL-17 and post-treatment pain level in chronic periapical lesions. Materials and methods Eighty patients with chronic apical lesions less than 1 cm were randomly assigned to receive NAC tablets (400 mg, ibuprofen tablets (400 mg, NAC (400 mg/ibuprofen (200 mg combination and placebo 90 minutes prior to sampling. Periapical exudates were collected from root canals. TNF- α, IL-6 and IL-17 levels were determined by ELISA and post-treatment pain was assessed using a visual analog scale (VAS. Results There was a significant difference in IL-6 level between ibuprofen group and placebo (p = 0.019. Significant difference in IL-17 level was observed between NAC/ibuprofen combination group and placebo (p = 0.043. Four hours after treatment, a significant difference was observed in VAS pain score between ibuprofen group and placebo (p = 0.017. Eight hours post-treatment, VAS pain score for NAC group was statistically lower than placebo group (p = 0.033. After 12 hours VAS pain score showed a significant decrease in NAC group compared to placebo (p = 0.049. Conclusion The prophylactic ibuprofen and NAC failed to clearly reflect their effect on cytokines levels in exudates of chronic periapical lesions. On the other hand it seems that NAC can be a substitute for ibuprofen in the management of post endodontic pain.

  14. Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

    Science.gov (United States)

    Markworth, James F.; Vella, Luke; Lingard, Benjamin S.; Tull, Dedreia L.; Rupasinghe, Thusitha W.; Sinclair, Andrew J.; Maddipati, Krishna Rao

    2013-01-01

    Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0–3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2α, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a

  15. Formulation and evaluation of a novel matrix-type orally disintegrating Ibuprofen tablet.

    Science.gov (United States)

    Tayebi, Hoda; Mortazavi, Seyed Alireza

    2011-01-01

    Orally disintegrating tablets (ODTs) are capable of turning quickly into a liquid dosage form in contact with the saliva, thus possessing the advantages of both the solid dosage forms particularly stability and liquid dosage forms specially ease of swallowing and pre-gastric absorption of drug. The aim of this study was to prepare a novel matrix-type buccal fast disintegrating ibuprofen tablet formulation using special polymers, water soluble excipients, super-disintegrants and quickly soluble granules. For this purpose different tablet formulations of ibuprofen were prepared. The amount of ibuprofen in each formulation was 100 mg. Eight groups of formulation were prepared (A-H series), accounting for a total number of 45 formulations. Formulations prepared were examined in terms of different physicochemical tests including powder/granule flowability, appearance, thickness, uniformity of weight, hardness, friability and disintegration time. Results of formulation F22a (in series F), was found to be acceptable, making it the chosen formulation for further studies. Then, by adding various flavorants and sweeteners to this formulation, complementary series of formulations, named G and H, were prepared. Following the comparison of their taste with each other through asking 10 volunteers, the most suitable formulation regarding the taste, being formulation F22s, was chosen as the ultimate formulation. This formulation had PVP, ibuprofen and croscarmellose as the intra-granular components and xylitol and saccharin as the extra-granular ingredients. Formulation F22s was found to be acceptable in terms of physicochemical tests conducted, showing quick disintegration within the buccal cavity, appropriate hardness and rather low friability. Hence formulation F22s was selected as the final formulation.

  16. [Cost-effectiveness analysis of celecoxib versus non-selective non-steroidal anti-inflammatory drug therapy for the treatment of osteoarthritis in Spain: A current perspective].

    Science.gov (United States)

    De Lossada, A; Oteo-Álvaro, Á; Giménez, S; Oyagüez, I; Rejas, J

    2016-01-01

    To assess the cost-effectiveness of celecoxib and non-selective non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis in clinical practice in Spain. A decision-tree model using distribution, doses, treatment duration and incidence of GI and CV events observed in the pragmatic PROBE-designed «GI-Reasons» trial was used for cost-effectiveness. Effectiveness was expressed in terms of event averted and quality-adjusted life-years (QALY) gained. QALY were calculated based on utility decrement in case of any adverse events reported in GI-Reasons trial. The National Health System perspective in Spain was applied; cost calculations included current prices of drugs plus cost of adverse events occurred. The analysis was expressed as an incremental cost-effectiveness ratio per QALY gained and per event averted. One-way and probabilistic analyses were performed. Compared with non-selective non-steroidal anti-inflammatory drugs, at current prices, celecoxib treatment had higher overall treatment costs €201 and €157, respectively. However, celecoxib was associated with a slight increase in QALY gain and significantly lower incidence of gastrointestinal events (pcost-effectiveness ratio of €13,286 per QALY gained and €4,471 per event averted. Sensitivity analyses were robust, and confirmed the results of the base case. Celecoxib at current price may be considered as a cost-effective alternative vs. non-selective non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis in daily practice in the Spanish NHS. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Treatment with acetaminophen/paracetamol or ibuprofen alleviates post-dose symptoms related to intravenous infusion with zoledronic acid 5 mg.

    Science.gov (United States)

    Wark, J D; Bensen, W; Recknor, C; Ryabitseva, O; Chiodo, J; Mesenbrink, P; de Villiers, T J

    2012-02-01

    Patients treated with intravenous zoledronic acid 5 mg for osteoporosis may experience post-dose influenza-like symptoms. Oral acetaminophen/paracetamol or ibuprofen administered 4 h post-infusion reduced the proportion of patients with increased oral temperature and worsening post-infusion symptom scores vs. placebo, thus providing an effective strategy for the treatment of such symptoms. Once-yearly intravenous zoledronic acid 5 mg is a safe and effective treatment for postmenopausal osteoporosis. This study assessed whether transient influenza-like post-dose symptoms associated with intravenous infusion of zoledronic acid can be reduced by post-dose administration of acetaminophen/paracetamol or ibuprofen. In an international, multicenter, randomized, double-blind, double-dummy parallel-group study, bisphosphonate-naïve postmenopausal women with osteopenia (n = 481) were randomized to receive zoledronic acid 5 mg + acetaminophen/paracetamol (n = 135), ibuprofen (n = 137) or placebo (n = 137), or placebo + placebo (n = 72). Acetaminophen/paracetamol and ibuprofen were administered every 6 h for 3 days beginning 4 h post-infusion. The proportion of patients with increased oral temperature (≥1°C above 37.5°C) and with worsening post-infusion symptom scores over 3 days was significantly lower in patients receiving ibuprofen (36.8% and 48.5%) or acetaminophen/paracetamol (37.3% and 46.3%) vs. those receiving placebo (63.5% and 75.9%, respectively; all p paracetamol or ibuprofen. Oral acetaminophen/paracetamol or ibuprofen effectively managed the transient influenza-like symptoms associated with zoledronic acid 5 mg.

  18. In situ forming hydrogels for intra-articular delivery of celecoxib: from polymer design to in vivo studies

    NARCIS (Netherlands)

    Petit, A.

    2014-01-01

    The main topic of this thesis was the development and evaluation of an injectable in situ forming gel made of acylated PCLA-PEG-PLCA copolymers for the local and sustained release of celecoxib, which is to date the drug of choice for the treatment of OA (Chapter 1). As shown in this thesis, the

  19. A famciclovir + celecoxib combination treatment is safe and efficacious in the treatment of fibromyalgia

    Directory of Open Access Journals (Sweden)

    Pridgen WL

    2017-02-01

    Full Text Available William L Pridgen,1 Carol Duffy,2 Judy F Gendreau,3 R Michael Gendreau3 1Innovative Med Concepts, LLC, 2Department of Biological Sciences, University of Alabama, Tuscaloosa, AL, 3Gendreau Consulting, LLC, Poway, CA, USA Objective: Infections and other stressors have been implicated in the development of fibromyalgia. We hypothesized that these stressors could result in recurrent reactivations of latent herpes virus infections, which could lead to the development of fibromyalgia. This study evaluated a famciclovir + celecoxib drug combination (IMC-1, active against suspected herpes virus reactivation and infection, for the treatment of fibromyalgia.Methods: A total of 143 fibromyalgia patients were enrolled at 12 sites in a 16-week, double-blinded, placebo-controlled proof-of-concept trial. Randomized patients received either IMC-1 or placebo in a 1:1 ratio. Outcome measures included a 24-hour recall pain Numerical Rating Scale, the Revised Fibromyalgia Impact Questionnaire (FIQ-R, the Patient’s Global Impression of Change (PGIC questionnaire, the Multidimensional Fatigue Inventory, the NIH Patient-Reported Outcomes Measurement Information System (PROMIS, and the Beck Depression Inventory-II conducted at baseline and weeks 6, 12, and 16 of the study.Results: A significant decrease in fibromyalgia-related pain was observed for patients on IMC-1 treatment versus placebo. PGIC response rates were significantly improved with IMC-1 treatment. Overall, patient self-reported functioning, as measured by the FIQ-R, was significantly improved. Fatigue was also significantly improved as measured by the PROMIS fatigue inventory. The safety profile was encouraging. Despite the celecoxib component of IMC-1, gastrointestinal and nervous system treatment emergent adverse events were reported less frequently in the IMC-1 group, and study completion rates favored IMC-1 treatment.Conclusion: IMC-1 was efficacious and safe in treating symptoms of fibromyalgia

  20. Formulation and delivery strategies of ibuprofen: challenges and opportunities.

    Science.gov (United States)

    Irvine, Jake; Afrose, Afrina; Islam, Nazrul

    2018-02-01

    Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is mostly administered orally and topically to relieve acute pain and fever. Due to its mode of action this drug may be useful in the treatment regimens of other, more chronic conditions, like cystic fibrosis. This drug is poorly soluble in aqueous media and thus the rate of dissolution from the currently available solid dosage forms is limited. This leads to poor bioavailability at high doses after oral administration, thereby increasing the risk of unwanted adverse effects. The poor solubility is a problem for developing injectable solution dosage forms. Because of its poor skin permeability, it is difficult to obtain an effective therapeutic concentration from topical preparations. This review aims to give a brief insight into the status of ibuprofen dosage forms and their limitations, particle/crystallization technologies for improving formulation strategies as well as suggesting its incorporation into the pulmonary drug delivery systems for achieving better therapeutic action at low dose.

  1. Combined use of an ibuprofen-releasing foam dressing and silver dressing on infected leg ulcers

    DEFF Research Database (Denmark)

    Jorgensen, B.; Gottrup, F.; Karlsmark, T.

    2008-01-01

    OBJECTIVE: To investigate the effect and safety of an ibuprofen-releasing foam (Biatain-Ibu, Coloplast A/S) combined with an ionised silver-releasing wound contact layer (Physiotulle Ag, Coloplast A/S) on painful, infected venous leg ulcers. METHOD: This open non-comparative study involved 24...... patients with painful, exuding, locally infected, and stalled venous leg ulcers. Persistent pain and pain at dressing change were monitored using a 11-point numerical box scale (NBS). The composition of the wound bed, the dressing combination's ability to absorb exudate and minimise leakage, ibuprofen...... dressing application, the mean concentration of ibuprofen in the wound exudate reached a constant level of 35 +/- 21 microg/ml.After 31 days, the relative wound area had reduced by 42%, with an associated decrease in fibrin and an increase in granulation tissue.The number of patients with wound malodour...

  2. In Vivo Dissolution and Systemic Absorption of Immediate Release Ibuprofen in Human Gastrointestinal Tract under Fed and Fasted Conditions.

    Science.gov (United States)

    Koenigsknecht, Mark J; Baker, Jason R; Wen, Bo; Frances, Ann; Zhang, Huixia; Yu, Alex; Zhao, Ting; Tsume, Yasuhiro; Pai, Manjunath P; Bleske, Barry E; Zhang, Xinyuan; Lionberger, Robert; Lee, Allen; Amidon, Gordon L; Hasler, William L; Sun, Duxin

    2017-12-04

    In vivo drug dissolution in the gastrointestinal (GI) tract is largely unmeasured. The purpose of this clinical study was to evaluate the in vivo drug dissolution and systemic absorption of the BCS class IIa drug ibuprofen under fed and fasted conditions by direct sampling of stomach and small intestinal luminal content. Expanding current knowledge of drug dissolution in vivo will help to establish physiologically relevant in vitro models predictive of drug dissolution. A multilumen GI catheter was orally inserted into the GI tract of healthy human subjects. Subjects received a single oral dose of ibuprofen (800 mg tablet) with 250 mL of water under fasting and fed conditions. The GI catheter facilitated collection of GI fluid from the stomach, duodenum, and jejunum. Ibuprofen concentration in GI fluid supernatant and plasma was determined by LC-MS/MS. A total of 23 subjects completed the study, with 11 subjects returning for an additional study visit (a total of 34 completed study visits). The subjects were primarily white (61%) and male (65%) with an average age of 30 years. The subjects had a median [min, max] weight of 79 [52, 123] kg and body mass index of 25.7 [19.4, 37.7] kg/m 2 . Ibuprofen plasma levels were higher under fasted conditions and remained detectable for 28 h under both conditions. The AUC 0-24 and C max were lower in fed subjects vs fasted subjects, and T max was delayed in fed subjects vs fasted subjects. Ibuprofen was detected immediately after ingestion in the stomach under fasting and fed conditions until 7 h after dosing. Higher levels of ibuprofen were detected in the small intestine soon after dosing in fasted subjects compared to fed. In contrast to plasma drug concentration, overall gastric concentrations remained higher under fed conditions due to increased gastric pH vs fasting condition. The gastric pH increased to near neutrality after feedingbefore decreasing to acidic levels after 7 h. Induction of the fed state reduced systemic

  3. Comparison of diclofenac-emulgel local application with oral ibuprofen administration for the treatment of active interphalangeal hand joints osteoarthritis (Heberden and/or Bushar nodules

    Directory of Open Access Journals (Sweden)

    J Zacher

    2007-01-01

    Full Text Available Objective. To assess efficacy and tolerability of diclofenac-emulgel local application in comparison with oral ibuprofen administration for the treatment of active interphalangeal hand joints osteoarthritis (Heberden and/or Bushar nodules. Material and methods. 321 pts were randomized into two groups. Diclofenac-emulgel (active drug and placebo ibuprofen tablets were administered in one of them, placebo diclofenac-emulgel and ibuprofen tablets (active drug — in the other. Diclofenac was administered as 10 cm strip locally 4 times a day and 400 mg of ibuprofen were given 3 times a day. Frequency of improvement was used as the main outcome measure. Improvement was registered if pain on 100 mm visual analog scale decreased at least by 40%. Disease activity, pain at rest, pain at movement, morning stiffness, grip strength and quality of life were used as additional outcome measures. Results. To the end of treatment according to 5% lower equivalency limit local therapy was at least as effective as oral administration of ibuprofen (p=0,007. Administration of both treatment methods provided also comparable improvement of all additional outcome measures. Both treatment methods showed good tolerability but more pts with receiving ibuprofen experienced serious adverse events than those using diclofenac (9 and 4 pts respectively. There was also similar proportion of pts prematurely withdrawn due to side effects (n=21: 5 (3% from them received diclofenac and 16 (10% - ibuprofen. Similar ratio of adverse events attributed to study treatment was revealed. Such events were present in 2 pts using diclofenac and in 13 (8,3% receiving ibuprofen. Most of these events applied to gastrointestinal tract (in 1 pt using diclofenac and in 8 pts receiving ibuprofen. Conclusion. Local treatment of active interphalangeal hand joints osteoarthritis (Heberden and/or Bushar nodules with diclofenac is at least as effective as systemic administration of ibuprofen

  4. Influence of acetaminophen and ibuprofen on in vivo patellar tendon adaptations to knee extensor resistance exercise in older adults

    DEFF Research Database (Denmark)

    Carroll, Chad C; Dickinson, Jared M; Lemoine, Jennifer K

    2011-01-01

    Millions of older individuals consume acetaminophen or ibuprofen daily and these same individuals are encouraged to participate in resistance training. Several in vitro studies suggest that cyclooxygenase-inhibiting drugs can alter tendon metabolism and may influence adaptations to resistance...... training. Thirty-six individuals were randomly assigned to a Placebo (67±2y), Acetaminophen (64±1y; 4000mg(.)d(-1)), or Ibuprofen (64±1y; 1200mg(.)d(-1)) group in a double-blind manner and completed 12-weeks of knee extensor resistance-training. Before and after training in vivo patellar tendon properties......, and this response was not influenced with ibuprofen consumption. Mean tendon CSA increased with training in the Acetaminophen group (3%, p0.05) with training in the Placebo group. These responses were generally uninfluenced by ibuprofen consumption. In the Acetaminophen group, tendon deformation and strain...

  5. [Recurrent aseptic meningitis secondary to taking ibuprofen and ketorolac].

    Science.gov (United States)

    Cano Vargas-Machuca, E; Mondéjar-Marín, B; Navarro-Muñoz, S; Pérez-Molina, I; Garrido-Robres, J A; Alvarez-Tejerina, A

    Aseptic meningitis is a process that is characterised by an inflammatory reaction of the meninges that is not due to any infectious agent. Its aetiology is varied and is most frequently caused by rheumatologic and/or autoimmune processes, chemical or medication-induced meningitis, the most notable drugs involved being antibiotics and non-steroidal anti-inflammatory drugs (NSAI). We report the case of a 70-year-old male, with no relevant history, who was admitted to hospital five times over a period of 16 months because of acute meningitis with polymorphonuclear pleocytosis, high protein levels in cerebrospinal fluid and normal glucose in cerebrospinal fluid. No evidence of an infectious causation, chemical meningitis, carcinomatosis or autoimmune disease was found and the patient was diagnosed with recurrent aseptic meningitis. It was found that the patient had taken ibuprofen or ketorolac on several occasions, a few hours before the appearance of symptoms. These episodes were quickly resolved after withdrawal of this medication. A number of NSAI have been reported as inducers of aseptic meningitis, one of the most notable being ibuprofen. We report the case of a patient who, as a consequence of taking ibuprofen and ketorolac, presented episodes of recurrent aseptic meningitis. To our knowledge this side effect of ketorolac has not been reported before. Its clinical features are impossible to differentiate from those of infectious meningitis. Diagnosis is reached by exclusion and a careful pharmacological study, including over-the-counter drugs like some of the NSAI, must be performed in patients with this condition, since it is a problem that can easily be solved by withdrawing the drug that causes it.

  6. Biodegradation of ibuprofen, diclofenac and carbamazepine in nitrifying activated sludge under 12 °C temperature conditions

    Energy Technology Data Exchange (ETDEWEB)

    Kruglova, Antonina; Ahlgren, Pia; Korhonen, Nasti; Rantanen, Pirjo; Mikola, Anna; Vahala, Riku

    2014-11-15

    Pharmaceuticals constitute a well-known group of emerging contaminants with an increasing significance in water pollution. This study focuses on three pharmaceuticals extensively used in Finland and which can be found in environmental waters: ibuprofen, diclofenac and carbamazepine. Biodegradation experiments were conducted in a full-scale Wastewater Treatment Plant (WWTP) and in laboratory-scale Sequencing Batch Reactors (SBRs). The SBRs were operated at 12 °C, with a sludge retention time (SRT) 10–12 d and organic loading rates (OLRs) of 0.17, 0.27 and 0.33 kg BOD{sub 7} m{sup -3}d{sup -1}. Ibuprofen was found to biodegrade up to 99%. The biodegradation rate constants (k{sub biol}) for ibuprofen were calculated for full-scale and laboratory processes as well as under different laboratory conditions and found to differ from 0.9 up to 5.0 l g{sub SS}{sup −1} d{sup −1}. Diclofenac demonstrated an unexpected immediate drop of concentration in three SBRs and partial recovery of the initial concentration in one of the reactors. High fluctuating in diclofenac concentration was presumably caused by removal of this compound under different concentrations of nitrites during development of nitrifying activated sludge. Carbamazepine showed no biodegradation in all the experiments. - Highlights: • The biodegradation of three pharmaceuticals examined under 12 °C conditions. • k{sub biol} constants for ibuprofen proposed for full-scale and laboratory-scale processes. • Influence of OLR on ibuprofen biodegradation was studied. • Removal followed by recovery of diclofenac detected in nitrifying activated sludge.

  7. Biodegradation of ibuprofen, diclofenac and carbamazepine in nitrifying activated sludge under 12 °C temperature conditions

    International Nuclear Information System (INIS)

    Kruglova, Antonina; Ahlgren, Pia; Korhonen, Nasti; Rantanen, Pirjo; Mikola, Anna; Vahala, Riku

    2014-01-01

    Pharmaceuticals constitute a well-known group of emerging contaminants with an increasing significance in water pollution. This study focuses on three pharmaceuticals extensively used in Finland and which can be found in environmental waters: ibuprofen, diclofenac and carbamazepine. Biodegradation experiments were conducted in a full-scale Wastewater Treatment Plant (WWTP) and in laboratory-scale Sequencing Batch Reactors (SBRs). The SBRs were operated at 12 °C, with a sludge retention time (SRT) 10–12 d and organic loading rates (OLRs) of 0.17, 0.27 and 0.33 kg BOD 7 m -3 d -1 . Ibuprofen was found to biodegrade up to 99%. The biodegradation rate constants (k biol ) for ibuprofen were calculated for full-scale and laboratory processes as well as under different laboratory conditions and found to differ from 0.9 up to 5.0 l g SS −1 d −1 . Diclofenac demonstrated an unexpected immediate drop of concentration in three SBRs and partial recovery of the initial concentration in one of the reactors. High fluctuating in diclofenac concentration was presumably caused by removal of this compound under different concentrations of nitrites during development of nitrifying activated sludge. Carbamazepine showed no biodegradation in all the experiments. - Highlights: • The biodegradation of three pharmaceuticals examined under 12 °C conditions. • k biol constants for ibuprofen proposed for full-scale and laboratory-scale processes. • Influence of OLR on ibuprofen biodegradation was studied. • Removal followed by recovery of diclofenac detected in nitrifying activated sludge

  8. Therapeutical Administration of Peptide Pep19-2.5 and Ibuprofen Reduces Inflammation and Prevents Lethal Sepsis

    Science.gov (United States)

    Barcena Varela, Sergio; Ferrer-Espada, Raquel; Reiling, Norbert; Goldmann, Torsten; Gutsmann, Thomas; Mier, Walter; Schürholz, Tobias; Drömann, Daniel; Brandenburg, Klaus; Martinez de Tejada, Guillermo

    2015-01-01

    Sepsis is still a major cause of death and many efforts have been made to improve the physical condition of sepsis patients and to reduce the high mortality rate associated with this disease. While achievements were implemented in the intensive care treatment, all attempts within the field of novel therapeutics have failed. As a consequence new medications and improved patient stratification as well as a thoughtful management of the support therapies are urgently needed. In this study, we investigated the simultaneous administration of ibuprofen as a commonly used nonsteroidal anti-inflammatory drug (NSAID) and Pep19-2.5 (Aspidasept), a newly developed antimicrobial peptide. Here, we show a synergistic therapeutic effect of combined Pep19-2.5-ibuprofen treatment in an endotoxemia mouse model of sepsis. In vivo protection correlates with a reduction in plasma levels of both tumor necrosis factor α and prostaglandin E, as a likely consequence of Pep19-2.5 and ibuprofen-dependent blockade of TLR4 and COX pro-inflammatory cascades, respectively. This finding is further characterised and confirmed in a transcriptome analysis of LPS-stimulated human monocytes. The transcriptome analyses showed that Pep19-2.5 and ibuprofen exerted a synergistic global effect both on the number of regulated genes as well as on associated gene ontology and pathway expression. Overall, ibuprofen potentiated the anti-inflammatory activity of Pep19-2.5 both in vivo and in vitro, suggesting that NSAIDs could be useful to supplement future anti-sepsis therapies. PMID:26197109

  9. Chiral auxiliary-mediated enantioenrichment of (+-)-ibuprofen, under Steglich conditions, with secondary alcohols derived from (R)-carvone

    Energy Technology Data Exchange (ETDEWEB)

    Amongero, Marcela; Visnovezky, Damian; Kaufman, Teodoro S., E-mail: kaufman@iquir-conicet.gov.a [Instituto de Quimica Rosario (IQUIR, CONICET-UNR) (Argentina); Universidad Nacional de Rosario (Argentina)

    2010-07-01

    The synthesis of a series of chiral secondary alcohols derived from (R)-carvone, and the stereochemical outcome of their reaction with (+-)-ibuprofen, is reported. The racemic drug was transformed into the corresponding diastereomeric esters mediated by DCC/DMAP, affording up to 5.7:1 diastereomeric ratios of the esters derived from either (S)- or (R)-ibuprofen, depending on the type of chiral auxiliary employed. (author)

  10. Chiral auxiliary-mediated enantioenrichment of (+-)-ibuprofen, under Steglich conditions, with secondary alcohols derived from (R)-carvone

    International Nuclear Information System (INIS)

    Amongero, Marcela; Visnovezky, Damian; Kaufman, Teodoro S.

    2010-01-01

    The synthesis of a series of chiral secondary alcohols derived from (R)-carvone, and the stereochemical outcome of their reaction with (±)-ibuprofen, is reported. The racemic drug was transformed into the corresponding diastereomeric esters mediated by DCC/DMAP, affording up to 5.7:1 diastereomeric ratios of the esters derived from either (S)- or (R)-ibuprofen, depending on the type of chiral auxiliary employed. (author)

  11. Evaluation of hepatic metabolism and pharmacokinetics of ibuprofen in rats under chronic hypobaric hypoxia for targeted therapy at high altitude.

    Science.gov (United States)

    Gola, Shefali; Gupta, Asheesh; Keshri, Gaurav K; Nath, Madhu; Velpandian, Thirumurthy

    2016-03-20

    With studies indicative of altered drug metabolism and pharmacokinetics (DMPK) under high altitude (HA)-induced hypobaric hypoxia, consideration of better therapeutic approaches has continuously been aimed in research for HA related illness management. DMPK of drugs like ibuprofen may get affected under hypoxia which establishes the requirement of different therapeutic dose regimen to ensure safe and effective therapy at HA. This study examined the effects of the chronic hypobaric hypoxia (CHH) on hepatic DMPK of ibuprofen in rats. Experimental animals were exposed to simulated altitude of 7620 m (∼25,000 ft) for CHH exposure (7 or 14 days) in decompression chamber and administered with ibuprofen (80 mg/kg, body weight, p.o.). Results demonstrated that CHH significantly altered PK variables of ibuprofen and activities of both phase-I and II hepatic metabolic enzymes as compared to the animals under normoxic conditions. Hepatic histopathological observations also revealed marked alterations. Increase in pro-inflammatory cytokines/chemokines viz. IL-1β, IL-2, IFN-γ, TNF-α exhibited close relevance with diminished CYP2C9 expression under CHH. Moreover, the down-regulated CYP2C9 level further supported the underlying mechanism for reduced metabolism of ibuprofen and as a result, increased retention of parent drug in the system. Increased mean retention time, Vd, T½ of ibuprofen, and decreased AUC, Cmax and clearance during CHH further strengthened the present findings. In conclusion, CHH exposure significantly affects hepatic DMPK of ibuprofen, which may further influence the usual therapeutic dose-regimen. Further, there is requirement of human studies to evaluate their susceptibility toward hypobaric hypoxia. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Antipyretic efficacy and tolerability of oral ibuprofen, oral dipyrone and intramuscular dipyrone in children: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Judith Prado

    Full Text Available CONTEXT AND OBJECTIVE: Dipyrone is a widely used over-the-counter antipyretic in Latin America, and elsewhere among Latin immigrants. Despite limited evidence, physicians often prescribe oral ibuprofen or intramuscular dipyrone as the most effective antipyretics. Our aim was to compare the antipyretic efficacy and tolerability of a single dose of oral ibuprofen, oral dipyrone or intramuscular dipyrone in febrile children. DESIGN AND SETTING: Randomized, single-blind clinical trial, at San Bartolomé Mother-Child National Teaching Hospital, Lima, Peru. METHODS: Children from six months to six years old with fever (rectal temperature: 38.3 to 39.8° C in the emergency ward between February and June 2003 were eligible. Seventy-five children were randomly assigned to receive a single dose of oral ibuprofen (10 mg/kg, oral dipyrone (15 mg/kg or intramuscular dipyrone (15 mg/kg. The primary outcome was mean temperature reduction after 30, 45, 60, 90 and 120 minutes. Secondary outcomes were fever-associated symptoms and clinical adverse events. RESULTS: Fever decreased by about 0.5° C after 45 minutes and by about 1.0° C after 120 minutes in all three groups. Mean temperatures were similar for the three groups at all times. There was a significant decrease in fever-associated symptoms for all groups. Six patients (four receiving oral dipyrone and two receiving ibuprofen were withdrawn because of vomiting within 20 minutes after first dose of study medication. One patient assigned to oral ibuprofen presented transient urticaria. CONCLUSIONS: Antipyretic efficacy and tolerability were similar for oral ibuprofen, oral dipyrone and intramuscular dipyrone. Oral antipyretics seem more appropriate for feverish children.

  13. Combined isosorbide dinitrate and ibuprofen as a novel therapy for muscular dystrophies: evidence from Phase I studies in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Cossu MV

    2014-05-01

    Full Text Available Maria Vittoria Cossu,1 Dario Cattaneo,1 Serena Fucile,1 Paolo Pellegrino,1 Sara Baldelli,1 Valeria Cozzi,1 Amedeo Capetti,2 Emilio Clementi1,3 1Unit of Clinical Pharmacology, Consiglio Nazionale delle Ricerche Institute of Neuroscience, Department of Biomedical and Clinical Sciences, University Hospital “Luigi Sacco”, Università di Milano, Milan, Italy; 2Unit of Infectious Diseases, University Hospital “Luigi Sacco”, Milan, Italy; 3Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy Abstract: We designed two Phase I studies that assessed healthy volunteers in order to evaluate the safety and to optimize the dosing of the combination of the drugs isosorbide dinitrate, a nitric oxide donor, and ibuprofen, a nonsteroidal antiinflammatory drug. We designed these studies with the aim of designing a Phase II trial to evaluate the drugs’ efficacy in patients affected by Duchenne muscular dystrophy. For the first trial, ISOFEN1, a single-dose, randomized-sequence, open-label, active control, three-treatment cross-over study, was aimed at comparing the pharmacokinetics of ibuprofen 200 mg and isosorbide dinitrate 20 mg when given alone and concomitantly. The pharmacokinetics of ibuprofen given alone versus ibuprofen given concomitantly with isosorbide dinitrate were similar, as documented by the lack of statistically significant differences in the main drug’s pharmacokinetic parameters (time to maximal concentration [Tmax], maximal concentration [Cmax], area under the curve [AUC]0–t, and AUC0–∞. Similarly, we found that the coadministration of ibuprofen did not significantly affect the pharmacokinetics of isosorbide dinitrate. No issues of safety were detected. The second trial, ISOFEN2, was a single-site, dose titration study that was designed to select the maximum tolerated dose for isosorbide dinitrate when coadministered with ibuprofen. Eighteen out of the 19 enrolled subjects tolerated the treatment well, and

  14. Effect of Secondary Equilibria on the Adsorption of Ibuprofen Enantiomers on a Chiral Stationary Phase with a Grafted Antibiotic Eremomycin

    Science.gov (United States)

    Reshetova, E. N.; Asnin, L. D.; Kachmarsky, K.

    2018-02-01

    The chromatographic separation of ibuprofen enantiomers on a Nautilus-E chiral stationary phase with a grafted eremomycin antibiotic at high column loading is accompanied by distortion of the shape of chromatographic peaks. A model is proposed to explain this phenomenon. A number of factors are considered in the model: the ionization of ibuprofen in the mobile phase, the pH change in the mass transfer zone caused by ionization, and competitive adsorption involving buffer components. Simulations performed using this model within the theory of nonequilibrium chromatography allow the shape of chromatograms for large amounts of S- and R-ibuprofen samples to be predicted. The adsorption mechanism is found to be mainly ion-exchange. The contribution from the molecular adsorption of ibuprofen to the total retention is shown to be several percent.

  15. Patient-reported outcomes of therapy with two brands of ibuprofen

    Directory of Open Access Journals (Sweden)

    Nwidu LL

    2008-09-01

    Full Text Available Objective: To investigate patients’ reported outcome following medication with two brands of 400 mg ibuprofen used to alleviate musculoskeletal pains.Methods: Adult peasant manual laborers (85 who met criteria were randomly assigned to receive either of the brands (A or B. Data on pain alleviation were gathered using the Short-Form McGill Pain Questionnaire (SF-MPQ, Visual Analogue Scale (VAS, Present Pain Intensity (PPI, and Clinical Global Impression of Improvement (CGII scales. Interval data obtained from the two brands were compared using the Students’ t-test at 95% confidence interval.Results: There were 42 participants, mean age=29.2 (SD=1.37 assigned to brand A and 43 (mean age=28.8 SD=1.14 in brand B of ibuprofen 400 mg. Brand B was consistently rated higher than brand A. Scores for medication efficacy were 10.4 (SD=1.65 (brand A and 11.4 (SD=1.68 (brand B; t=2.768, P=0.007. Alleviation of pain symptoms: 10.8 (SD=1.64 and 11.6 (SD=1.72; t = 2.194, P=0.031. Similarly, rated scores on the impact of pain on quality of life were 10.5 (SD=2.00 and 12.1 (SD=1.85; t=3.830, P<0.001. There was a reduction in Present Pain Intensity scores by 32.7% and 34.3% for Brand A and brand B participants respectively. The decrease in Visual Analog pain scale score was 35.9% and 37.3% for brand A and brand B participants respectively. The decrease in SF-MPQ was by 85.1% and 69.9% for the brand A and brand B groups respectively. The clinical global impression of improvement for both groups of patients indicated an improvement rate of 71.4% and 61.9% for brand A and 81.4% and 74.4% for brand B participants. Conclusion: This clinical study infers that though the two brands of ibuprofen 400 mg are legally pharmaceutical equivalent, they are not clinically equivalent. In most of the parameters evaluated, brand B was rated more efficacious than brand A. This explains the patients’ preferences and demand for this brand of ibuprofen in the Nigerian community.

  16. Comparative assessment of chewing gum and ibuprofen in the management of orthodontic pain with fixed appliances: A pragmatic multicenter randomized controlled trial.

    Science.gov (United States)

    Ireland, Anthony J; Ellis, Pamela; Jordan, Abbie; Bradley, Rebecca; Ewings, Paul; Atack, Nikki E; Griffiths, Helen; House, Kate; Moore, Matthew; Deacon, Scott; Wenger, Nick; Worth, Victoria; Scaysbrook, Emma; Sandy, Jonathan R

    2016-08-01

    The aim of this randomized trial was to investigate the effect of the use of a sugar-free chewing gum vs ibuprofen on reported pain in orthodontic patients. This was a 2-arm parallel design randomized controlled trial in 9 sites in the southwest of England. Patients about to undergo orthodontic treatment with maxillary and mandibular fixed appliances were recruited and randomly allocated to an experimental chewing gum group or a control ibuprofen group. Eligibility criteria included patients undergoing fixed maxillary and mandibular appliance therapy, aged 11 to 17 years, and able to use ibuprofen and chewing gum. The primary outcome measure was pain experienced after appliance placement using a mean of 3 recordings on a scale of 0 to 10. Secondary outcome measures were pain experienced in the subsequent 3 days, pain after the first archwire change, ibuprofen use, and appliance breakages. Pain scores were recorded with a questionnaire and posted to a collection center by each patient. Randomization was by means of a central telephone service and comprised computer-generated random numbers used to generate a sequential allocation list, with permuted blocks of variable size (2 and 4) and stratified by center. Neither the clinicians nor the patients were blinded to the intervention. Patients in the control group were permitted to use ibuprofen only, and patients in the experimental group were allowed to use ibuprofen if they did not get sufficient analgesia from the chewing gum. Data were analyzed using the principle of intention to treat with multilevel modeling to reflect the structured nature of the data (scores within patient within site). One thousand patients were recruited and randomized in a ratio of 1:1 to the chewing gum and ibuprofen (control) groups. The male-to-female ratios were similar in the groups. The pain questionnaire response rates were good at approximately 84% and 83% after appliance placement (chewing gum group, 419; ibuprofen group, 407) and

  17. Enantioselective adsorption of ibuprofen and lysine in metal-organic frameworks

    NARCIS (Netherlands)

    Bueno-Perez, R.; Martin-Calvo, A.; Gómez-Álvarez, P.; Gutiérrez-Sevillano, J.J.; Merkling, P.J.; Vlugt, T.J.H.; van Erp, T.S.; Dubbeldam, D.; Calero, S.

    2014-01-01

    This study reveals the efficient enantiomeric separation of bioactive molecules in the liquid phase. Chiral structure HMOF-1 separates racemic mixtures whereas heteroselectivity is observed for scalemic mixtures of ibuprofen using non-chiral MIL-47 and MIL-53. Lysine enantiomers are only separated

  18. A Study of Analgesic Efficacy of Ibuprofen and Diclofenac Sodium in Acute Pulpitis Patients

    Directory of Open Access Journals (Sweden)

    G Komali

    2014-01-01

    Results: Time of onset of action of drugs, Time to peak effect, Total analgesic effect and tolerability of the drugs were assessed. From the present study it was found that there were statistically significant differences in the onset of action of drug and Time to peak effect. Onset of action was early in Ibuprofen and Time to peak effect was early in Diclofenac sodium. Patients rated both drugs to be equally good on Global evaluation scales. Conclusion: It was found that Diclofenac Sodium is more potent compared to Ibuprofen.

  19. An ibuprofen-antagonized plasmin inhibitor released by human endothelial cells.

    Science.gov (United States)

    Rockwell, W B; Ehrlich, H P

    1991-02-01

    Serum-free culture medium harvested from endothelial cell monolayer cultures derived from human scars and dermis was examined for inhibition of fibrinolysis using a fibrin plate assay. Human cultured fibroblasts and smooth muscle cells did not produce any detectable inhibitory activity. The inhibitor is spontaneously released from the cultured endothelial cells over time. In the fibrin plate assay of plasmin-induced fibrinolysis, one nonsteroidal antiinflammatory (NSAI) drug, ibuprofen, was demonstrated to antagonize the inhibition of fibrinolysis. The antagonistic activity of ibuprofen appears unrelated to its NSAI drug activity because other NSAI drugs such as indomethacin and tolmetin have minimal antagonistic activity. Heating the cultured endothelial cells to 42 degrees C stimulates greater release of the inhibitor in a shorter period of time. This plasmin inhibitor, which is produced by endothelial cells, may contribute to postburn vascular occlusion, leading to secondary progressive necrosis in burn-traumatized patients.

  20. Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Necek Magdalena

    2008-05-01

    Full Text Available Abstract Background Antipyretic drugs are widely used in children with fever, though there is a controversy about the benefit of reducing fever in children with malaria. In order to assess the effect of ibuprofen on fever compared to placebo in children with uncomplicated Plasmodium falciparum malaria in Gabon, a randomized double blind placebo controlled trial, was designed. Methods Fifty children between two and seven years of age with uncomplicated malaria were included in the study. For the treatment of fever, all patients "received" mechanical treatment when the temperature rose above 37.5°C. In addition to the mechanical treatment, continuous fanning and cooling blanket, patients were assigned randomly to receive ibuprofen (7 mg/kg body weight, every eight hours or placebo. Results The fever clearance time using a fever threshold of 37.5°C was similar in children receiving ibuprofen compared to those receiving placebo. The difference was also not statistically significant using a fever threshold of 37.8°C or 38.0°C. However, the fever time and the area under the fever curve were significantly smaller in the ibuprofen group compared to the placebo group. Conclusion Ibuprofen is effective in reducing the time with fever. The effect on fever clearance is less obvious and depends on definition of the fever threshold. Trial registration The trial registration number is: NCT00167713

  1. Temperature and pH Responsive Microfibers for Controllable and Variable Ibuprofen Delivery

    Directory of Open Access Journals (Sweden)

    Toan Tran

    2015-01-01

    Full Text Available Electrospun microfibers (MFs composed of pH and temperature responsive polymers can be used for controllable and variable delivery of ibuprofen. First, electrospinning technique was employed to prepare poly(ε-caprolactone (PCL and poly(N-isopropylacrylamide-co-methacrylic acid (pNIPAM-co-MAA MFs containing ibuprofen. It was found that drug release rates from PCL MFs cannot be significantly varied by either temperature (22–40°C or pH values (1.7–7.4. In contrast, the ibuprofen (IP diffusion rates from pNIPAM-co-MAA MFs were very sensitive to changes in both temperature and pH. The IP release from pNIPAM-co-MAA MFs was highly linear and controllable when the temperature was above the lower critical solution temperature (LCST of pNIPAM-co-MAA (33°C and the pH was lower than the pKa of carboxylic acids (pH 2. At room temperature, however, the release rate was dramatically increased by nearly ten times compared to that at higher temperature and lower pH. Such a unique and controllable drug delivery system could be naturally envisioned to find many practical applications in biomedical and pharmaceutical sciences such as programmable transdermal drug delivery.

  2. A simple Ultraviolet spectrophotometric method for the determination of etoricoxib in dosage formulations

    Directory of Open Access Journals (Sweden)

    Shipra Singh

    2012-01-01

    Full Text Available The present study was undertaken to develop a validated, rapid, simple, and low-cost ultraviolet (UV spectrophotometric method for estimating Etoricoxib (ETX in pharmaceutical formulations. The analysis was performed on λ max 233 nm using 0.1 M HCl as blank/diluent. The proposed method was validated on International Conference on Harmonization (ICH guidelines including parameters as linearity, accuracy, precision, reproducibility, and specificity. The proposed method was also used to access the content of the ETX in two commercial brands of Indian market. Beer′s law was obeyed in concentration range of 0.1-0.5 μg/ml, and the regression equation was Y = 0.418x + 0.018. The mean accuracy values for 0.1 μg/ml and 0.2 μg/ml concentration of ETX were found to be 99.76 ± 0.52% and 99.12 ± 0.84, respectively, and relative standard deviation (RSD of interday and intraday was less than 2%. The developed method was suitable and specific to the analysis of ETX even in the presence of common excipients. The method was applied on two different marketed brands and ETX contents were 98.5 ± 0.56 and 99.33 ± 0.44, respectively, of labeled claim. The proposed method was validated as per ICH guidelines and statistically good results were obtained. This method can be employed for routine analysis of ETX in bulk and commercial formulations.

  3. A simple Ultraviolet spectrophotometric method for the determination of etoricoxib in dosage formulations.

    Directory of Open Access Journals (Sweden)

    S Singh

    2012-01-01

    Full Text Available The present study was undertaken to develop a validated, rapid, simple, and low-cost ultraviolet (UV spectrophotometric method for estimating Etoricoxib (ETX in pharmaceutical formulations. The analysis was performed on Î max 233 nm using 0.1 M HCl as blank/diluent. The proposed method was validated on International Conference on Harmonization (ICH guidelines including parameters as linearity, accuracy, precision, reproducibility, and specificity. The proposed method was also used to access the content of the ETX in two commercial brands of Indian market. Beer′s law was obeyed in concentration range of 0.1-0.5 μg/ml, and the regression equation was Y = 0.418x + 0.018. The mean accuracy values for 0.1 μg/ml and 0.2 μg/ml concentration of ETX were found to be 99.76 ± 0.52% and 99.12 ± 0.84, respectively, and relative standard deviation (RSD of interday and intraday was less than 2%. The developed method was suitable and specific to the analysis of ETX even in the presence of common excipients. The method was applied on two different marketed brands and ETX contents were 98.5 ± 0.56 and 99.33 ± 0.44, respectively, of labeled claim. The proposed method was validated as per ICH guidelines and statistically good results were obtained. This method can be employed for routine analysis of ETX in bulk and commercial formulations.

  4. Formulation of Novel Layered Sodium Carboxymethylcellulose Film Wound Dressings with Ibuprofen for Alleviating Wound Pain

    Directory of Open Access Journals (Sweden)

    Lenka Vinklárková

    2015-01-01

    Full Text Available Effective assessment and management of wound pain can facilitate both improvements in healing rates and overall quality of life. From a pharmacological perspective, topical application of nonsteroidal anti-inflammatory drugs in the form of film wound dressings may be a good choice. Thus, the aim of this work was to develop novel layered film wound dressings containing ibuprofen based on partially substituted fibrous sodium carboxymethylcellulose (nonwoven textile Hcel NaT. To this end, an innovative solvent casting method using a sequential coating technique has been applied. The concentration of ibuprofen which was incorporated as an acetone solution or as a suspension in a sodium carboxymethylcellulose dispersion was 0.5 mg/cm2 and 1.0 mg/cm2 of film. Results showed that developed films had adequate mechanical and swelling properties and an advantageous acidic surface pH for wound application. An in vitro drug release study implied that layered films retained the drug for a longer period of time and thus could minimize the frequency of changing the dressing. Films with suspended ibuprofen demonstrated higher drug content uniformity and superior in vitro drug release characteristics in comparison with ibuprofen incorporation as an acetone solution. Prepared films could be potential wound dressings for the effective treatment of wound pain in low exuding wounds.

  5. Formulation of Novel Layered Sodium Carboxymethylcellulose Film Wound Dressings with Ibuprofen for Alleviating Wound Pain

    Science.gov (United States)

    Vinklárková, Lenka; Vetchý, David; Bernatonienė, Jurga

    2015-01-01

    Effective assessment and management of wound pain can facilitate both improvements in healing rates and overall quality of life. From a pharmacological perspective, topical application of nonsteroidal anti-inflammatory drugs in the form of film wound dressings may be a good choice. Thus, the aim of this work was to develop novel layered film wound dressings containing ibuprofen based on partially substituted fibrous sodium carboxymethylcellulose (nonwoven textile Hcel NaT). To this end, an innovative solvent casting method using a sequential coating technique has been applied. The concentration of ibuprofen which was incorporated as an acetone solution or as a suspension in a sodium carboxymethylcellulose dispersion was 0.5 mg/cm2 and 1.0 mg/cm2 of film. Results showed that developed films had adequate mechanical and swelling properties and an advantageous acidic surface pH for wound application. An in vitro drug release study implied that layered films retained the drug for a longer period of time and thus could minimize the frequency of changing the dressing. Films with suspended ibuprofen demonstrated higher drug content uniformity and superior in vitro drug release characteristics in comparison with ibuprofen incorporation as an acetone solution. Prepared films could be potential wound dressings for the effective treatment of wound pain in low exuding wounds. PMID:26090454

  6. Effects of low-dose ibuprofen supplementation and resistance training on bone and muscle in postmenopausal women: A randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Whitney R.D. Duff

    2016-12-01

    Full Text Available Purpose: To compare the effects of nine months of exercise training and ibuprofen supplementation (given immeditately after exercise sessions on bone and muscle in postmenopausal women. Methods: In a double-blind randomized trial, participants (females: n = 90, mean age 64.8, SD 4.3 years were assigned (computer generated, double blind to receive supervised resistance training or stretching 3 days/week, and ibuprofen (400 mg, post-exercise or placebo (i.e. 4 groups for 9 months. In this proof-of-concept study the sample size was halved from required 200 identified via 90% power calculation. Baseline and post-intervention testing included: Dual energy x-ray absorptiometry (DXA for lumbar spine, femoral neck, and total body areal bone mineral density (aBMD; geometry of proximal femur; total body lean tissue and fat mass; predicted 1-repetition maximum muscle strength testing (1RM; biceps curl, hack squat. Results: Exercise training or ibuprofen supplementation had no effects on aBMD of the lumbar spine, femoral neck, and total body. There was a significant exercise × supplement × time interaction for aBMD of Ward's region of the femoral neck (p = 0.015 with post hoc comparison showing a 6% decrease for stretching with placebo vs. a 3% increase for stretching with ibuprofen (p = 0.017. Resistance training increased biceps curl and hack squat strength vs. stretching (22% vs. 4% and 114% vs. 12%, respectively (p < 0.01 and decreased percent body fat compared to stretching (2% vs. 0% (p < 0.05. Conclusions: Ibuprofen supplementation provided some benefits to bone when taken independent of exercise training in postmenopausal women. This study provides evidence towards a novel, easily accessible stimulus for enhancing bone health [i.e. ibuprofen]. Keywords: Aging, Osteoporosis, Sarcopenia, Ibuprofen

  7. Ibuprofen abates cypermethrin-induced expression of pro-inflammatory mediators and mitogen-activated protein kinases and averts the nigrostriatal dopaminergic neurodegeneration.

    Science.gov (United States)

    Singh, Ashish; Tripathi, Pratibha; Prakash, Om; Singh, Mahendra Pratap

    2016-12-01

    Cypermethrin induces oxidative stress, microglial activation, inflammation and apoptosis leading to Parkinsonism in rats. While ibuprofen, a non-steroidal anti-inflammatory drug, relieves from inflammation, its efficacy against cypermethrin-induced Parkinsonism has not yet been investigated. The study aimed to explore the protective role of ibuprofen in cypermethrin-induced Parkinsonism, an environmentally relevant model of Parkinson's disease (PD), along with its underlying mechanism. Animals were treated with/without cypermethrin in the presence/absence of ibuprofen. Behavioural, immunohistochemical and biochemical parameters of Parkinsonism and expression of pro-inflammatory and pro-apoptotic proteins along with mitogen-activated protein kinases (MAPKs) were determined. Ibuprofen resisted cypermethrin-induced behavioural impairments, striatal dopamine depletion, oxidative stress in the nigrostriatal tissues and loss of the nigral dopamine producing cells and increase in microglial activation along with atypical expression of pro-inflammatory and apoptotic proteins that include cyclooxygenase-2, tumour necrosis factor-α, MAPKs (c-Jun N-terminal kinase, p38 and extracellular signal-regulated kinase), B cell lymphoma 2-associated protein X, tumour suppressor protein p53, cytochrome c and caspase-3 in the nigrostriatal tissue. The results obtained thus demonstrate that ibuprofen lessens inflammation and regulates MAPKs expression thereby averts cypermethrin-induced Parkinsonism.

  8. Efficacy of nano- and microemulsion-based topical gels in delivery of ibuprofen: an in vivo study.

    Science.gov (United States)

    Azizi, Mosayeb; Esmaeili, Fariba; Partoazar, Alireza; Ejtemaei Mehr, Shahram; Amani, Amir

    2017-03-01

    Nanoemulsion has shown many advantages in drug delivery systems. In this study, for the first time, analgesic and anti-inflammatory properties of a nanomelusion of almond oil with and without ibuprofen was compared with corresponding microemulsion and commercial topical gel of the drug using formalin and carrageenan tests, respectively. Almond oil (oil phase) was mixed with Tween 80 and Span 80 (surfactants), and ethanol (co-surfactant) and them distilled water (aqueous phase) was then added to the mixture at once. Prepared nanoemulsions were pre-emulsified into a 100 ml beaker using magnet/stirrer (1000 rpm). Then, using a probe ultrasonicator (Hielscher UP400s, Hielscher, Ringwood, NJ) the nanoemulsions were formed. The optimised nanoemulsion formulation containing 2.5% ibuprofen, showed improved analgesic and anti-inflammatory effects compared with commercial product and corresponding microemulsion product containing 5% ibuprofen (i.e. twice the content of ibuprofen in the nanoemulsion) in vivo. The nanoemulsion preparation showed superior analgesic activities during chronic phase. Also, it decreased the inflammation from the first hour, while the microemulsion and the commercial product started to show their anti-inflammatory effects after 2 and 3 h, respectively. Our finding suggests that the size of the emulsion particles must be considered as an important factor in topical drug delivery systems.

  9. [Has the use of antipyretics been modified after the introduction of different concentrations of ibuprofen into the market?].

    Science.gov (United States)

    García Blanes, C P; Rodríguez-Cantón Pascual, P; Morales-Carpi, C; Morales-Olivas, F J

    2014-12-01

    Due to the emergence of new pharmaceutical presentations of ibuprofen (40 mg/ml), an analysis was made on the use of antipyretics in pediatric outpatient in Spain. A cross-sectional, observational, descriptive study was carried out on a sample of children under 14 years old with treated febrile syndrome, seen in the Emergency Room of the Hospital General Universitario de Valencia from November 2012 to January 2013. Of the 217 children included, 144 were treated with paracetamol or ibuprofen, 69 received both drugs, and one received paracetamol and metamizol. There were 58.7% of exposures to paracetamol and 40.9% to ibuprofen. The parents decided the use of antipyretics in 63.2% of cases. In 98 exposures the dose was different from that authorized in the labeling of the drug (off-label use). Ibuprofen was used off-label in 40.2% of cases, mostly by underdosing (35.9%). Paracetamol was used off-label in 29.8% of cases, predominantly overdose (26.8%), with the difference being statistically significant. No significant differences were observed in the off-label use in either monotherapy or combined use. There were also no differences when antipyretics prescribed by doctors or given directly by parents were evaluated separately. The majority of children with treated febrile syndrome seen in the Emergency Room were receiving antipyretic drugs after a parental decision. Paracetamol is the most commonly used drug and one in three children received it simultaneously with ibuprofen. The antipyretics were used off label in one-third of the cases. Off label use of ibuprofen is increasing, and is probably due to the existence of different pharmaceutical presentations. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  10. Paracetamol, Ibuprofen, and Recurrent Major Cardiovascular and Major Bleeding Events in 19 120 Patients With Recent Ischemic Stroke.

    Science.gov (United States)

    Gonzalez-Valcarcel, Jaime; Sissani, Leila; Labreuche, Julien; Bousser, Marie-Germaine; Chamorro, Angel; Fisher, Marc; Ford, Ian; Fox, Kim M; Hennerici, Michael G; Mattle, Heinrich P; Rothwell, Peter M; Steg, Philippe Gabriel; Vicaut, Eric; Amarenco, Pierre

    2016-04-01

    The presumed safety of paracetamol in high-cardiovascular risk patients has been questioned. We determined whether paracetamol or ibup