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Celecoxib
Kinds of Celecoxib Selected AbstractsCelecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study,,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2008Fabiano G. Nery Abstract Objective To investigate whether the cox-2 inhibitor celecoxib has antidepressant effects in bipolar disorder (BD) patients during depressive or mixed phases. Methods We studied 28 DSM-IV BD patients who were experiencing a depressive or mixed episode and were on a stable dose of a mood stabilizer or atypical antipsychotic medication. Subjects were randomized to receive 6 weeks of double-blind placebo or celecoxib (400,mg/day) treatment. Current mood stabilizer or antipsychotic medication remained at the same doses during the trial. Results Intention-to-treat analysis showed that the patients receiving celecoxib had lower Hamilton Depression Rating Scale (HamD) scores after 1 week of treatment compared to the patients receiving placebo, but this difference was not statistically significant (p,=,0.09). The improvement in the first week of treatment was statistically significant when the analysis included only the subjects who completed the full 6-week trial (p,=,0.03). The two groups did not differ significantly on depressive or manic symptoms from the second week until the end of the trial. Celecoxib was well tolerated with the exception of two subjects who dropped out of the study due to rash. Conclusions Our findings suggest that adjunctive treatment with celecoxib may produce a rapid-onset antidepressant effect in BD patients experiencing depressive or mixed episodes. Copyright © 2008 John Wiley & Sons, Ltd. [source] Celecoxib-induced photoallergic drug eruptionINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2004Ayca Cordan Yazici MD Photoallergic dermatitis is caused by a photosensitizing substance plus sunlight exposure in a sensitized person. If the photosensitizer is delivered internally, it is called a photoallergic drug reaction. Celecoxib is a new generation non-steroidal anti-inflammatory drug and sulfonamide derivative. We report a photoallergic drug eruption associated with the introduction of celecoxib. To our knowledge, this is the first report of photoallergic drug reaction associated with celecoxib. [source] Experimental study of the safety of the selective COX-2 inhibitor, celecoxib, for gastric mucosaJOURNAL OF DIGESTIVE DISEASES, Issue 2 2003Jun Ting LI OBJECTIVE: To compare the gastric mucosal damage induced by a COX-2 inhibitor, celecoxib, and a conventional NSAID, indomethacin. METHODS: A rat model of NSAID-induced gastric mucosal damage was prepared for indomethacin and celecoxib separately (n = 8). After gastric damage was induced by 100% ethanol, celecoxib was administered by gastric gavage (n = 8). Gastric mucosal concentrations of 6-keto-PGF1, and TXB2 and the lesion index (LI) were measured. Morphological changes of the gastric mucosa were assessed under light and scanning electron microscopy. RESULTS: Indomethacin caused marked gastric damage (LI: 13.38 ± 2.06) and significant reduction of the concentrations of 6-keto-PGF1, and TXB2 (P < 0.01), Celecoxib did not produce necrotic injuries on healthy gastric mucosa (LI: 0), but the mucosal injuries previously induced by ethanol worsened after its administration (LI: 37.19 ± 3.34 vs 19.90 ± 2.28, P < 0.01). CONCLUSIONS: Inhibition of COX-1 is the major mechanism of NSAIDs in producing gastric mucosal damage. As a selective COX-2 inhibitor, celecoxib does not produce toxic injuries of the healthy gastric mucosa, and is thus safer than conventional NSAID. However, when administered in the presence of an altered gastric mucosa, gastric injuries were worsened. [source] Cancer "photo-chemoprevention" with pulsed dye laser and celecoxib,LASERS IN SURGERY AND MEDICINE, Issue 3 2003Zhi Wang MD Abstract Background and Objectives Our previous study demonstrated the efficacy of pulsed dye laser (PDL) in inhibiting cancer growth. This study is to determine the synergic effect of PDL and Celecoxib, when they are combined for treatment of oral cancer. Study Design/Materials and Methods Fifteen mice were inoculated with oral cell carcinoma and divided into three groups of five each (30 seeding sites/group): (1) control (no treatment), (2) PDL only, and (3) treatment with combined PDL and Celecoxib (1,500 ppm). The number and volume of tumors were counted and measured for 21 days. Results The combined treatment developed tumor at the slowest rate. On day 21, the average tumor volumes were (1) 483.6 mm3 (control), (2) 312.1 mm3 (PDL only), and (3) 151.4 mm3 (combined treatment). Conclusions A synergic effect was found in the combined treatment group. This study provides the first evidence of the efficacy of a new strategy for the treatment of oral cancer, namely, cancer "photo-chemoprevention." Lasers Surg. Med. 32:180,184, 2003. © 2003 Wiley-Liss, Inc. [source] A systematic review of COX-2 inhibitors compared with traditional NSAIDs, or different COX-2 inhibitors for post-operative painACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2004J. Rømsing Background:, We have reviewed the analgesic efficacy of cyclooxygenase-2 (COX-2) inhibitors compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs), different COX-2 inhibitors, and placebo in post-operative pain. Methods:, Randomized controlled trials were evaluated. Outcome measures were pain scores and demand for supplementary analgesia 0,24 h after surgery. Results:, Thirty-three studies were included in which four COX-2 inhibitors, rofecoxib 50 mg, celecoxib 200 and 400 mg, parecoxib 20, 40 and 80 mg, and valdecoxib 10, 20, 40, 80 mg were evaluated. Ten of these studies included 18 comparisons of rofecoxib, celecoxib, or parecoxib with NSAIDs. Rofecoxib 50 mg and parecoxib 40 mg provided analgesic efficacy comparable to that of the NSAIDs in the comparisons, and with a longer duration of action after dental surgery but possibly not after major procedures. Celecoxib 200 mg and parecoxib 20 mg provided less effective pain relief. Four studies included five comparisons of rofecoxib 50 mg with celecoxib 200 and 400 mg. Rofecoxib 50 mg provided superior analgesic effect compared with celecoxib 200 mg. Data on celecoxib 400 mg were too sparse for firm conclusions. Thirty-three studies included 62 comparisons of the four COX-2 inhibitors with placebo and the COX-2 inhibitors significantly decreased post-operative pain. Conclusion:, Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in post-operative pain after minor and major surgical procedures, and after dental surgery these COX-2 inhibitors have a longer duration of action. Besides, rofecoxib 50 mg provides superior analgesic effect compared with celecoxib 200 mg. [source] Quantitative assessment of the gastrointestinal and cardiovascular risk-benefit of celecoxib compared to individual NSAIDs at the population level,,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2007Cristina Varas-Lorenzo MD Abstract Purpose To estimate the net cardiovascular (CV) (coronary heart disease, stroke, congestive heart failure), and gastrointestinal (GI) (peptic ulcer complications) risk-benefit public health impact of the use of celecoxib compared to non-selective NSAIDs in the arthritis population. Methods We applied discrete event simulation models to data from the US National Health Surveys, CV risk-prediction models from the Framingham Heart Study, and population-based studies. Models took into account the multifactorial effect of risk factors, comorbidity, and competing risk of mortality. We simulated the natural history of CV and GI disease in the U.S. arthritis population over 1 year, through the individual baseline cardiovascular and gastrointestinal risk profile. This model was modified with relative risks associated with the use of each treatment. The mean number of events was estimated for each end-point in each model: natural history, celecoxib, diclofenac, ibuprofen, naproxen. The number of events for celecoxib was compared with each NSAID. Results The evaluation included 1% of the U.S. population with arthritis. Celecoxib, when applied to 100,000 patients over 1 year, resulted in 570 (range from sensitivity analysis: 440,691), 226 (124,313), and 746 (612,868) fewer ulcer complications than diclofenac, ibuprofen, and naproxen, respectively. There were 20 (16,25), 8 (4,12), and 27 (22,32) fewer deaths from ulcer complications, respectively. No increase in cardiovascular events or all cause mortality was observed for celecoxib versus the other individual NSAIDs. Conclusion Results from these simulations suggest a gastrointestinal benefit for celecoxib not offset by increased cardiovascular events or mortality. The methodology used here provides a risk-benefit assessment framework for evaluating the public heath impact of drugs. Copyright © 2006 John Wiley & Sons, Ltd. [source] Chemopreventive Effect of Celecoxib in Oral Precancers and Cancers,THE LARYNGOSCOPE, Issue 10 2006Lining Feng PhD Abstract Objectives: Oral cancer has become an important health care problem in many countries. Because this disease develops slowly, early detection and intervention can greatly affect ultimate outcome. Celecoxib is a cyclooxygenase-2 inhibitor with significantly less toxicity. This study investigated the possibility of using it for chemoprevention of oral cancer at the early stages. Study Design: Randomized animal study. Methods: Dysplastic lesions were induced in the buccal pouches of 47 hamsters by a 5 week painting of 9,10-dimethl-1,2-benzanthrancene (DMBA). Basal diets or diets containing 500 or 1,500 ppm of Celecoxib were orally given for 7 weeks. The T50 (50% incidence; i.e., the time to appearance of tumors in 50% of the hamsters) was observed, and volume of tumors was measured on day 1, 9, 19, 28, 35, and 48 with the Celecoxib treatment. Results: The T50 was 9, 19, and 28 days with the treatment in the control group, in the 500 ppm group, and in the 1,500 ppm group, respectively. It indicated that the Celecoxib treatment could delay progression of early lesion. The tumor measurement showed that this treatment was also effective in delaying tumor growth in both treatment groups. There was a difference in the treatment efficacy between the 500 ppm and 1,500 ppm of Celecoxib, indicating a dose-dependent efficacy. Conclusions: Celecoxib is effective in delaying onset of early lesions induced by DMBA and in slowing growth of the tumors in hamster cheek pouches during the postinitiation stage. Its treatment efficacy appears to be dose dependent. [source] Antiangiogenic and Chemopreventive Activities of Celecoxib in Oral Carcinoma Cell,,THE LARYNGOSCOPE, Issue 5 2002Zhi Wang MD Abstract Objectives Chemoprevention is a promising strategy to inhibit carcinoma before invasive tumors develop, but a new molecular target is desirable. Celecoxib is a newly developed cyclo-oxygenase (COX)-2 inhibitor with significantly less toxicity. The study was conducted to determine whether celecoxib is effective and safe in prevention of oral cancer. The antiangiogenic activity of celecoxib was studied to explore the potential mechanism involved. Study Design Randomized animal study. Methods The study consisted of two phases. In the phase 1, 10 mice were used to determine the efficacy and safety of celecoxib with intradermal inoculation with oral carcinoma cells. The 10 mice were equally divided into two groups 5 mice (30 inoculated sites) in each group to receive 1,500 parts per million (ppm) celecoxib mixed in with the diet or to eat a normal diet, respectively, for 21 days. In phase 2, 10 more mice were inoculated to determine the effect of celecoxib on angiogenesis. Five mice received 3,000 ppm celecoxib in the diet, with the other five mice as control animals. The antiangiogenic activity was evaluated by comparing the density of newly growing microvessels after the inoculation. Results The results indicated that celecoxib significantly delayed cell growth and reduced tumor volume. There was statistical significance in the quantity of new vasculature in the tumor sites between the two groups. No toxic effect was found by means of measurement of body weight loss and microscopic dissection of organs. Conclusions The study provided the first evidence to show the chemopreventive efficacy of celecoxib on oral cancer in a nude mouse model. Clinical trials are warranted to determine the efficacy in humans. [source] Potential antioxidant activity of celecoxib and amtolmetin guacyl: in vitro studiesAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1 2007M. Kirkova Summary 1,In vitro studies of the potential antioxidant activity of the selective cyclo-oxygenase-2 inhibitor celecoxib and the non-steroid anti-inflammatory drug amtolmetin guacyl (AMG) were carried out. The study included experiments on the ability of these drugs to affect some indices of the oxidative stress [lipid peroxidation (LP), activity of antioxidant enzymes, glutathione (GSH) level] in rat stomach and colon mucosa and in liver. 2,Celecoxib and AMG did not change the activity of the enzymes GSH-peroxidase, oxidased glutathione (GSSG)-reductase and glucose-6-phosphate-dehydrogenase, as well as the GSH level in all tissue preparations. An increased superoxide dismutase (SOD) activity and a tendency to a decreased Fe/ascorbic acid-induced LP in stomach and colon mucosa were found, but only in the presence of AMG. 3,In the liver, both celecoxib and AMG decreased spontaneous and Fe/ascorbic acid-induced LP. SOD activity was enhanced only in the presence of AMG. 4,Experiments aimed at studying celecoxib and AMG in free oxygen radical-generating systems were also carried out. AMG and tolmetin (the main metabolite of AMG) inhibited OH, -provoked deoxyribose degradation in a Fenton system. Celecoxib had no effect on free radicals when tested in the same system. 5,In conclusion, the results of the present in vitro studies suggest that AMG and celecoxib possess antioxidant and metal-chelating abilities, which might contribute to their beneficial effects. [source] Action of Celecoxib on Hepatic Metabolic Changes Induced by the Walker-256 Tumour in RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2007Alexandra Acco Celecoxib was administered daily (5,50 mg/kg body weight) beginning at the day in which the tumour cells were inocculated. At day 14, the liver was isolated and perfused in order to measure alanine transformation, glycolysis and arginine transformation. Maximal reduction of tumour growth (75%), accompanied by an almost normal weight gain, was attained with a celecoxib dose of 12.5 mg/kg. Diminution of glucose utilization (glycolysis) and inhibition of gluconeogenesis and ureogenesis from alanine caused by the tumor were totally reversed by celecoxib. Oxygen uptake by the liver was also normalized by the drug. Hepatic arginine transformation, which is normally enhanced in rats bearing the Walker-256 tumour, remained elevated in celecoxib-treated animals. It was concluded that preservation of gluconeogenesis and normalization of hepatic glucose utilization can explain, partly at least, the clinical improvement of cancer patients treated with the drug. The lack of action of celecoxib on arginine hydrolysis might indicate that reduction in polyamine synthesis is not a factor contributing to the diminished tumour growth. [source] Effect of celecoxib on cyclooxygenase-2 expression and possible variants in a patient with Barrett's esophagusDISEASES OF THE ESOPHAGUS, Issue 3 2007G. A. Jacobson SUMMARY., Cyclooxygenase-2 (COX-2) expression is increased in metaplastic and dysplastic Barrett's esophageal epithelium and it is thought that selective COX-2 inhibitors could offer hope as chemoprevention therapy. The aim of the study was to investigate the in vivo effect of celecoxib on COX-2 expression in patients with Barrett's esophagus and no recent history of non-steroidal anti-inflammatory drug use. Endoscopic mucosal biopsy specimens were collected at baseline and after 28 days of therapy in a patient treated with celecoxib 200 mg twice daily. Samples were analyzed for COX-2 expression by immunoblot analysis with chemiluminescence detection. COX-2 expression was found to decline 20% and 44% at two different biopsy sites compared to the baseline sample. Longer exposures revealed a number of previously unidentified proteins above and below the 67 kDa COX-2 protein including 38 kDa and 45 kDa proteins which were present only at study completion consistent with up-regulation after celecoxib therapy. Further investigations of the 38 kDa and 45 kDa proteins were undertaken using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) with immunoblot and MALDI-TOF (matrix assisted laser desorption ionization , time of flight) analysis but no matches were found and results were inconclusive. Unmatched masses from MALDI-TOF peptide mass fingerprinting were compared with human COX-2 (67 kDa) and COX-2b (39 kDa) using unspecific cleavage. Peptide sequence homology with COX-2 and COX-2b was found for a length of 19 amino acids. Based on immunodetection, molecular weight and equivical MALDI-TOF results, one of these up-regulated proteins may be COX-2b. [source] The use of in vitro technologies coupled with high resolution accurate mass LC-MS for studying drug metabolism in equine drug surveillanceDRUG TESTING AND ANALYSIS, Issue 1 2010James P. Scarth Abstract The detection of drug abuse in horseracing often requires knowledge of drug metabolism, especially if urine is the matrix of choice. In this study, equine liver/lung microsomes/S9 tissue fractions were used to study the phase I metabolism of eight drugs of relevance to equine drug surveillance (acepromazine, azaperone, celecoxib, fentanyl, fluphenazine, mepivacaine, methylphenidate and tripelennamine). In vitro samples were analyzed qualitatively alongside samples originating from in vivo administrations using LC-MS on a high resolution accurate mass Thermo Orbitrap Discovery instrument and by LC-MS/MS on an Applied Biosystems Sciex 5500 Q Trap. Using high resolution accurate mass full-scan analysis on the Orbitrap, the in vitro systems were found to generate at least the two most abundant phase I metabolites observed in vitro for all eight drugs studied. In the majority of cases, in vitro experiments were also able to generate the minor in vivo metabolites and sometimes metabolites that were only observed in vitro. More detailed analyses of fentanyl incubates using LC-MS/MS showed that it was possible to generate good quality spectra from the metabolites generated in vitro. These data support the suggestion of using in vitro incubates as metabolite reference material in place of in vivo post-administration samples in accordance with new qualitative identification guidelines in the 2009 International Laboratory Accreditation Cooperation-G7 (ILAC-G7) document. In summary, the in vitro and in vivo phase I metabolism results reported herein compare well and demonstrate the potential of in vitro studies to compliment, refine and reduce the existing equine in vivo paradigm. Copyright © 2010 John Wiley & Sons, Ltd. [source] Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study,,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2008Fabiano G. Nery Abstract Objective To investigate whether the cox-2 inhibitor celecoxib has antidepressant effects in bipolar disorder (BD) patients during depressive or mixed phases. Methods We studied 28 DSM-IV BD patients who were experiencing a depressive or mixed episode and were on a stable dose of a mood stabilizer or atypical antipsychotic medication. Subjects were randomized to receive 6 weeks of double-blind placebo or celecoxib (400,mg/day) treatment. Current mood stabilizer or antipsychotic medication remained at the same doses during the trial. Results Intention-to-treat analysis showed that the patients receiving celecoxib had lower Hamilton Depression Rating Scale (HamD) scores after 1 week of treatment compared to the patients receiving placebo, but this difference was not statistically significant (p,=,0.09). The improvement in the first week of treatment was statistically significant when the analysis included only the subjects who completed the full 6-week trial (p,=,0.03). The two groups did not differ significantly on depressive or manic symptoms from the second week until the end of the trial. Celecoxib was well tolerated with the exception of two subjects who dropped out of the study due to rash. Conclusions Our findings suggest that adjunctive treatment with celecoxib may produce a rapid-onset antidepressant effect in BD patients experiencing depressive or mixed episodes. Copyright © 2008 John Wiley & Sons, Ltd. [source] A celecoxib derivative inhibits focal adhesion signaling and induces caspase-8-dependent apoptosis in human acute myeloid leukemia cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2008Isolda Casanova Abstract Most acute myeloid leukemias (AMLs), including those with c-Kit or FLT3 mutations, show enhanced anchorage independent growth associated with constitutive activation of focal adhesion proteins. Moreover, these alterations increase cell survival, inhibit apoptosis and are associated with poor prognosis and resistance to chemotherapy. Therefore, the induction of apoptosis by selective inhibition of focal adhesion signaling may represent a novel anti-AML therapy. Here, we have evaluated the antitumor effect and the mechanism of action of celecoxib and E7123, a non-Cox-2 inhibitor derivative, in a panel of human AML cell lines and bone marrow mononuclear cells from AML patients. Both compounds induce cell death by inhibiting focal adhesion signaling through p130Cas, FAK and c-Src, leading to caspase-8 dependent apoptosis. This mechanism of action differs from that of classical cytotoxic drugs or of other targeted therapies, and is amenable to rational drug development. Therefore, both drugs could be developed as AML therapeutics; nevertheless, E7123 shows more activity than celecoxib against AML cells, and may not present its Cox-2 dependent cardiovascular toxicity. Finally, our results support the evaluation of celecoxib in AML patients, and the preclinical evaluation of E7123, before its possible clinical testing. © 2008 Wiley-Liss, Inc. [source] Short-term dietary administration of celecoxib enhances the efficacy of tumor lysate-pulsed dendritic cell vaccines in treating murine breast cancerINTERNATIONAL JOURNAL OF CANCER, Issue 9 2006Tobias Hahn Abstract Cyclooxygenase-2 (COX-2) is a rate-limiting enzyme in the synthesis of prostaglandins. It is over-expressed in multiple cancers and has been associated with diminished tumor immunity. Dendritic cells (DCs) are considered candidates for cancer immunotherapy due to their ability to process and present antigens to T cells and stimulate immune responses. However, DC-based vaccines have exhibited minimal effectiveness against established tumors. In this study, we evaluated the effect of short-term administration of the selective COX-2 inhibitor celecoxib on the efficacy of DC-based vaccines in preventing and treating established 4T1 murine mammary tumors. We show that dietary celecoxib alone significantly suppresses the growth of primary tumors and the incidence of lung metastases in the prophylactic setting but is less effective against pre-established tumors. However, we demonstrate that celecoxib administered after primary tumor establishment synergizes with tumor lysate-pulsed DC and the adjuvant, GM-CSF, to improve the antitumor immune response by suppressing primary tumor growth and markedly reducing the occurrence of lung metastases. This triple combination therapy elicits a tumor-specific immune response evidenced by elevated IFN-, and IL-4 secretion by CD4+ T cells and results in increased infiltration of CD4+ and CD8+ T cells to the tumor site. In addition, dietary celecoxib inhibits angiogenesis evidenced by decreased vascular proliferation within the tumor and serum vascular endothelial growth factor levels. These studies suggest that short-term celecoxib therapy in combination with DC vaccines may be safely used for treating metastatic breast cancer. © 2005 Wiley-Liss, Inc. [source] Cyclooxygenase-2 inhibitor celecoxib augments chemotherapeutic drug-induced apoptosis by enhancing activation of caspase-3 and -9 in prostate cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2005Devendra S. Dandekar Abstract Many tumors constitutively express high levels of the inducible form of proinflammatory enzyme, cyclooxygenase-2 (COX-2). Increased COX-2 expression is associated with tumor cell resistance to many cytotoxic chemotherapy drugs. Furthermore, increased resistance to cytotoxic antitumor drugs is also known to be dependent on associated stromal cells in many tumors. We investigated whether prostate tumor-associated stromal cells, marrow-derived osteoblasts, affect cytotoxicity of 2 antitumor drugs, COL-3 and docetaxel (TXTR), and whether it is dependent on COX-2 activity. We further examined whether inhibiting the activity of COX-2 negate the stroma-induced decrease in drug sensitivity in tumor cells. COX-2-specific inhibitor celecoxib (CXB) was used to inhibit COX-2 activity and associated alteration in cell death signaling was investigated. Coculturing PC-3ML cells with osteoblasts decreased the cytotoxicity of the tested antitumor drugs and was associated with increased COX-2 activity in PC-3ML cells. A significant decrease in drug-induced PGE2 increase and an increase in cytotoxicity were observed when cells were treated with COL-3 or TXTR combined with CXB. Cytotoxicity of single or combination treatment increased apoptosis, which was associated with caspase-3 and -9 activation, PARP cleavage, increased BAD protein, but decreased protein levels of XIAP and BCL- xL. Oral administration of CXB (40 mg/kg) to mice with PC-3ML tumors for 42 days increased tumor latency, decreased tumor growth and enhanced tumor control with COL-3 or TXTR. Overall, a synergistic enhancement of antitumor activity in combination treatment was observed in vitro and an additive effect in vivo. These observations suggest a potential clinical use of combined dosing of COX-2 inhibitors and cytotoxic drugs at lower, nontoxic dose than currently used to treat advanced prostate cancer. © 2005 Wiley-Liss, Inc. [source] Celecoxib-induced photoallergic drug eruptionINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2004Ayca Cordan Yazici MD Photoallergic dermatitis is caused by a photosensitizing substance plus sunlight exposure in a sensitized person. If the photosensitizer is delivered internally, it is called a photoallergic drug reaction. Celecoxib is a new generation non-steroidal anti-inflammatory drug and sulfonamide derivative. We report a photoallergic drug eruption associated with the introduction of celecoxib. To our knowledge, this is the first report of photoallergic drug reaction associated with celecoxib. [source] Combination of an EGFR blocker and a COX-2 inhibitor for the treatment of advanced cutaneous squamous cell carcinomaJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 12 2008Ahmad Jalili Summary Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers worldwide. Epidermal growth factor receptor (EGFR) is expressed at the cell surface by more than 90% of SCCs and its activation is responsible for cell cycle progression, proliferation, survival, angiogenesis and metastasis. Cyclooxygenase-2 (COX-2) is an enzyme up-regulated through EGFR signaling and responsible for some of the EGFR-dependent biological effects. An 88-year-old man presented with a recurrent, locoregionally meta-static SCC of the right parietal region, which was resistant to radiotherapy. With a combination therapy of an EGFR blocker (cetuximab) and a COX-2 inhibitor (celecoxib), the tumor regressed partially and the patient's Karnofsky index improved. We speculate that the combined use of cetuxi-mab and COX-2 inhibitors can be a new and effective therapy for advanced and recurrent cutaneous SCCs. [source] Cyclo-Oxygenase 2 Function Is Essential for Bone Fracture Healing,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2002Ann Marie Simon Abstract Despite the molecular and histological similarities between fetal bone development and fracture healing, inflammation is an early phase of fracture healing that does not occur during development. Cyclo-oxygenase 2 (COX-2) is induced at inflammation sites and produces proinflammatory prostaglandins. To determine if COX-2 functions in fracture healing, rats were treated with COX-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs) to stop COX-2-dependent prostaglandin production. Radiographic, histological, and mechanical testing determined that fracture healing failed in rats treated with COX-2-selective NSAIDs (celecoxib and rofecoxib). Normal fracture healing also failed in mice homozygous for a null mutation in the COX-2 gene. This shows that COX-2 activity is necessary for normal fracture healing and confirms that the effects of COX-2-selective NSAIDs on fracture healing is caused by inhibition of COX-2 activity and not from a drug side effect. Histological observations suggest that COX-2 is required for normal endochondral ossification during fracture healing. Because mice lacking Cox2 form normal skeletons, our observations indicate that fetal bone development and fracture healing are different and that COX-2 function is specifically essential for fracture healing. [source] Adding Gabapentin to a multimodal regimen does not reduce acute pain, opioid consumption or chronic pain after total hip arthroplastyACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2009H. CLARKE Background: Gabapentin (GPN) is effective in reducing post-operative pain and opioid consumption, but its effects with regional anesthesia for total hip arthroplasty (THA) are not known. We designed this study to determine whether (1) gabapentin administration reduces pain and opioid use after THA using a multimodal analgesic regimen including spinal anesthesia; (2) pre-operative administration of gabapentin is more effective than post-operative administration. Methods: After REB approval and informed consent, 126 patients were enrolled in a double-blinded, randomized-controlled study. Patients received acetaminophen 1 g per os (p.o.), celecoxib 400 mg p.o. and dexamethasone 8 mg intravenously, 1,2 h pre-operatively. Patients were randomly assigned to one of three treatment groups (G1: Placebo/Placebo; G2: GPN/Placebo; G3: Placebo/GPN). Patients received gabapentin 600 mg (G2) or placebo (G1 and G3) 2 h before surgery. All patients had spinal anesthesia [15 mg (3cc) of 0.5% hypobaric bupivacaine with 10 ,g of fentanyl]. In the post-anesthetic care unit, patients received gabapentin 600 mg (G3) or placebo (G1 and G2). On the ward, patients received acetaminophen 1000 mg p.o. q6h, celecoxib 200 mg p.o. q12h and a morphine PCA device. Patients were interviewed 6 months post-surgery to determine the incidence and severity of chronic post-surgical pain. Results: Mean±SD cumulative morphine (mg) consumption (G1=49.4±24.8, G2=47.2±30.1 and G3=56.1±38.2) at 48 h and pain scores at 12, 24, 36 and 48 h post-surgery were not significantly different among the groups [G1 (n=38), G2 (n=38) and G3 (n=38)]. Side effect profiles were similar across groups. Six months after surgery, the number of patients who reported chronic post-surgical pain (G1=10, G2=12 and G3=9) and the severity of the pain (G1=4.2±2.9, G2=4.1±2.2 and G3=4.9±2.2) did not differ significantly among the groups (P>0.05). Conclusions: A single 600 mg dose of gabapentin given pre-operatively or post-operatively does not reduce morphine consumption or pain scores in hospital or at 6 months after hip arthroplasty within the context of spinal anesthesia and a robust multimodal analgesia regimen. [source] Experimental study of the safety of the selective COX-2 inhibitor, celecoxib, for gastric mucosaJOURNAL OF DIGESTIVE DISEASES, Issue 2 2003Jun Ting LI OBJECTIVE: To compare the gastric mucosal damage induced by a COX-2 inhibitor, celecoxib, and a conventional NSAID, indomethacin. METHODS: A rat model of NSAID-induced gastric mucosal damage was prepared for indomethacin and celecoxib separately (n = 8). After gastric damage was induced by 100% ethanol, celecoxib was administered by gastric gavage (n = 8). Gastric mucosal concentrations of 6-keto-PGF1, and TXB2 and the lesion index (LI) were measured. Morphological changes of the gastric mucosa were assessed under light and scanning electron microscopy. RESULTS: Indomethacin caused marked gastric damage (LI: 13.38 ± 2.06) and significant reduction of the concentrations of 6-keto-PGF1, and TXB2 (P < 0.01), Celecoxib did not produce necrotic injuries on healthy gastric mucosa (LI: 0), but the mucosal injuries previously induced by ethanol worsened after its administration (LI: 37.19 ± 3.34 vs 19.90 ± 2.28, P < 0.01). CONCLUSIONS: Inhibition of COX-1 is the major mechanism of NSAIDs in producing gastric mucosal damage. As a selective COX-2 inhibitor, celecoxib does not produce toxic injuries of the healthy gastric mucosa, and is thus safer than conventional NSAID. However, when administered in the presence of an altered gastric mucosa, gastric injuries were worsened. [source] Synthesis of [11C]celecoxib: a potential PET probe for imaging COX-2 expressionJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 12 2005Jaya Prabhakaran Abstract [11C]Labeling of celecoxib, a COX-2 selective inhibitor and prescription drug for arthritis and pain has been achieved. The precursor molecule for the radiolabeling was synthesized from 4-bromoacetophenone in 4 steps with 23% overall yield. Stille reaction of N-[bis -(4-methoxyphenyl)phenylmethyl]-4-[5-(4-tributylstannylphenyl)-3-trifluoromethylpyrazol-1-yl]benzenesulfonamide (5) with methyl iodide in presence of catalytic amounts of Pd2(dba)3, tri- o -tolylphosphine, CuCl and excess of K2CO3 in DMF followed by deprotection of the sulfonamide with 20% trifluoroaceticacid yielded 4-(5- p -tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonamide or celecoxib (6) in 30% yield. However, under identical conditions, synthesis of [11C]celecoxib ([11C]6) was unsuccessful. Instead, trapping [11C]CH3I in an argon purged solution of catalytic amounts of Pd2(dba)3 and tri- o -tolylphosphine followed by the addition of the precursor 5 in DMF under argon and heating the mixture at 135°C for 4 min resulted in the incorporation of [11C]CH3 group. Removal of the dimethoxytrityl (DMT) with 20% trifluoroacetic acid afforded [11C]celecoxib in 40 min (EOB) and 8±2% yield (EOB) along with a specific activity of 1080±180 Ci/mmol (n=6) (EOB). Copyright © 2005 John Wiley & Sons, Ltd. [source] Low-intensity pulsed ultrasound and nonsteroidal anti-inflammatory drugs have opposing effects during stress fracture repairJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 12 2007Jiliang Li Abstract Low-intensity pulsed ultrasound (LIPUS) and nonsteroidal anti-inflammatory drugs (NSAIDs) were used to treat stress fracture. Bilateral stress fractures were induced in the ulnas of 48 adult rats. Animals were divided into two groups (NSAID and VEH), and treated 5 days per week with celecoxib (5 mg/kg) mixed in a vehicle solution of polyethylene glycol and saline (NSAID) or vehicle alone (VEH). One-to-three hours following drug administration, all animals were treated with unilateral active-LIPUS and contralateral inactive-LIPUS. Equal numbers of ulnas from each drug group were histologically evaluated at 2, 4, and 8 weeks following induction of stress fracture. Neither LIPUS nor NSAID influenced bone resorption, but each had significant and opposite effects on intracortical bone formation rate. These effects indicate that LIPUS may be used to facilitate stress fracture repair whereas NSAID may delay tissue level repair of stress fractures. There was no interaction between LIPUS and NSAID, indicating that the beneficial LIPUS effect was not mediated by the cyclooxygenase-2 pathway. LIPUS accelerated stress fracture healing, whereas the NSAID delayed repair. When used in combination, the beneficial LIPUS effect was not impaired by the detrimental NSAID effect. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1559,1567, 2007 [source] PGE2 and IL-6 production by fibroblasts in response to titanium wear debris particles is mediated through a Cox-2 dependent pathwayJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2004Susan V. Bukata Aseptic loosening of orthopaedic implants is precipitated by wear debris-induced osteolysis. Central to this process are the pro-inflammatory mediators that are produced in response to wear by the fibroblastic cells, which comprise the majority of periprosthetic membranes. Since this pro-inflammatory cascade is mediated by a plethora of factors with redundant functions, it is imperative to establish a hierarchy. Two well-known fibroblast derived pro-inflammatory factors that stimulate wear debris-induced osteoclastic resorption are prostaglandin E2 (PGE2) and IL-6. However, their relationship to each other in this process is poorly defined. Here we show immunohistochemistry of retrieval membranes indicating that COX-2 is the principal cyclooxygenase responsible for PGE2 production in fibroblasts around failed implants. We also performed in vitro experiments with fibroblasts derived from wild-type (WT), COX-1 (,/,) and COX-2 (,/,) mice, which demonstrated that COX-2 is required for Ti wear debris-induced PGE2 production. Interestingly, COX-2 was also required for IL-6 production in these assays, which could be rescued by the addition of exogenous PGE2 (10,6 M). Pharmacology studies that utilized the COX-1 selective inhibitor SC 560, the COX-2 selective inhibitor celecoxib, and the nonselective COX inhibitor indomethacin confirmed these results. Taken together, these results indicate that selective inhibition of prostaglandin signaling could favorably impact aseptic loosening beyond its direct effects on PGE2 synthesis, in that it inhibits downstream pro-inflammatory/pro-osteoclastic cytokine production. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulationsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2007Héctor R. Guzmán Abstract Biopharmaceutical evaluation of crystalline celecoxib salts in novel solid formulations, which were designed to simultaneously facilitate dissolution and inhibit precipitation in vitro, showed fast and complete absorption in beagle dogs at doses up to 7.5 mg/kg orally. In contrast, 5 mg/kg celecoxib in the form of Celebrex® showed approximately 40% absolute bioavailability in a cross-over experiment. An in vitro,in vivo correlation was observed in dog, and a threshold level of in vitro dissolution needed to maximize in vivo performance was highlighted. Oral bioavailability was limited in the absence of excipient combinations that delayed precipitation of celecoxib free acid as the salt neutralized in the GI fluid. Formulations of crystal forms having high energy (a ,spring'), thus transiently increasing solubility in aqueous solution relative to the free acid, combined with excipients functioning as precipitation inhibitors (,parachutes') were shown to provide both enhanced dissolution and high oral bioavailability. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2686,2702, 2007 [source] The importance of brain PGE2 inhibition versus paw PGE2 inhibition as a mechanism for the separation of analgesic and antipyretic effects of lornoxicam in rats with paw inflammationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2009Dr Nobuko Futaki Abstract Objectives Lornoxicam is a non-selective cyclooxygenase inhibitor that exhibits strong analgesic and anti-inflammatory effects but a weak antipyretic effect in rat models. Our aim was to investigate the mechanism of separation of potencies or analgesic and antipyretic effecls of lornoxicam in relatioin to its effect on prostaglandin E2 (PGE2) production in the inflammatory paw and the brain. Methods A model of acute or chronic paw inflammation was induced by Freund's complete adjuvant injection into the rat paw. Lornoxicam (0.01,1 mg/kg), celecoxib (0.3,30 mg/kg) or loxoprofen (0.3,30 mg/kg) was administered orally to the rats and the analgesic and antipyretic effects were compared. The paw hyperalgesia was assessed using the Randall,Selitto test or the flexion test. Dorsal subcutaneous body temperature was measured as indicator of pyresis. After the measurement of activities, the rats were sacrificed and the PGE2 content in the paw exudate, cerebrospinal fluid or brain hypothalamus was measured by enzme-immunoassay. Key findings In a chronic model of arthritis, lornoxicam, celecoxib and loxoprofen reduced hyperalgesia with an effective dose that provides 50% inhibition (ED50) of 0.083, 3.9 and 4.3 mg/kg respectively, whereas the effective dose of these drugs in pyresis was 0.58, 0.31 and 0.71 mg/kg respectively. These drugs significantly reduced the PGE2 level in paw exudate and the cerebrospinal fluid. In acute oedematous rats, lornoxicam 0.16 mg/kg, celecoxib 4 mg/kg and loxoprofen 2.4 mg/kg significantly reduced hyperalgesia to a similar extent. On the other hand, lornnoxicam did not affect the elevated body temperature, whereas celecoxib and loxoprofen siginificantly reduced the pyrexia to almost the normal level. These drugs significantly reduced the PGE2 level in inflamed paw exudate lo almost the normal level. On the other hand, lornoxicam did not change PGE2 level in the brain hypothalamus, whereas celecoxib and loxoprofen strongly decreased it. Conclusions Lornoxicam exhibits strong analgesic but weak antipyretic effects in rats with paw inflammation. Such a separation of effects is related to its efficacy in the reduction of PGE2 levels in the paw and brain hypothalamus. [source] Efficacy of chitosan microspheres for controlled intra-articular delivery of celecoxib in inflamed jointsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2004Hetal Thakkar The use of polymeric carriers in formulations of therapeutic drug delivery systems has gained widespread application, due to their advantage of being biodegradable and biocompatible. In this study, we aimed to prepare celecoxib-loaded chitosan microspheres for intra-articular administration and to compare the retention of the celecoxib solution and chitosan microspheres in the joint cavity. The microspheres were characterized for entrapment efficiency, particle size and surface morphology by scanning electron microscopy. In-vitro drug release studies of microspheres revealed that the microspheres are able to control the release of celecoxib over a period of 96 h. Biodistribution studies of celecoxib and chitosan microspheres were performed by radiolabelling with 99mTc and injecting intra-articularly in rats. The study indicated that following intra-articular administration the distribution of the drug to the organs, like liver and spleen, is very rapid compared with that of the microspheres. Compared with the drug solution, a 10-fold increase in the concentration of the drug in the joint was observed 24 h post intra-articular injection (P < 0.005) when drug was encapsulated in microspheres. [source] Computer-aided design of selective COX-2 inhibitors: comparative molecular field analysis and docking studies of some 3,4-diaryloxazolone derivativesJOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 7 2001G. R. Desiraju Abstract The recent discovery of a second, inducible isoform of cyclooxygenase, COX-2, has stimulated the search for highly selective non-steroidal anti-inflammatory drugs (NSAIDs). These NSAIDs have the ability to treat pain and inflammation caused by arthritis with less risk of gastrointestinal or renal toxicity. We report here the results of 3D-quantitative structure,activity relationship and docking studies, performed on a series of 3,4-diaryloxazolones. Comparative moleculer field analysis studies provided a good model with cross-validated and conventional r2 values of 0.688 and 0.969 respectively for 24 analogues in the training set with six components. Docking studies with both COX-1 and COX-2 indicate good selectivity for COX-2. The binding energies between COX-2 and some of the most active oxazolones are comparable to those of celecoxib or rofecoxib. These compounds adopt similar orientations and form similar sets of hydrogen bonds involving the sulfonyl group of the ligand and His 90, Leu 352, Ser 353, Arg 513, Phe 518 and Ser 530 residues of the receptor. Copyright © 2001 John Wiley & Sons, Ltd. [source] Clinical trial: the impact of cyclooxygenase inhibitors on gastrointestinal recovery after major surgery , a randomized double blind controlled trial of celecoxib or diclofenac vs. placeboALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2009D. A. WATTCHOW Summary Background, Ileus occurs after abdominal surgery and may be severe. Inhibition of prostaglandin release reduces post-operative ileus in a rat model. Aim, To determine whether prostaglandin inhibition by cyclooxygenase inhibitors, celecoxib or diclofenac, could enhance gastrointestinal recovery and reduce post-operative ileus in humans. Methods, Two hundred and ten patients undergoing elective major abdominal surgery were randomized to receive twice daily placebo (n = 67), celecoxib (100 mg, n = 74) or diclofenac (50 mg, n = 69), preoperatively and continuing for up to 7 days. Primary outcomes were hallmarks of gut recovery. Secondary outcomes were paralytic ileus, pain and complications. Results, There was no clinically significant difference between the groups for restoration of bowel function. There was a significant reduction in paralytic ileus in the celecoxib-treated group (n = 1, 1%) compared with diclofenac (n = 7, 10%) and placebo (n = 9, 13%); P = 0.025, RR 0.20, CI 0.01,0.77. Pain scores, analgesia, transfusion requirements and adverse event rates were similar between study groups. Conclusions, Perioperative low dose celecoxib, but not diclofenac, markedly reduced the development of paralytic ileus following major abdominal surgery, but did not accelerate early recovery of bowel function. This was independent of narcotic use and had no increase in post-operative complications. [source] A randomized, placebo-controlled study of the effects of naproxen, aspirin, celecoxib or clopidogrel on gastroduodenal mucosal healingALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2009A. DIKMAN Summary Background, Many individuals with gastroduodenal ulcers require on-going, non-steroidal anti-inflammatory drug (NSAID) or anti-platelet therapy. Aims, To evaluate the effects of these agents on gastroduodenal mucosal healing. Methods,Helicobacter pylori -negative volunteers were randomized to receive naproxen, celecoxib, aspirin, clopidogrel or placebo. Antral and duodenal lesions were created endoscopically with a biopsy forceps. After 7 days of medication dosing, each lesion was scored [from 0 (low) to 8 (high)] using a validated methodology. The primary endpoint was the mean injury score. The secondary endpoint was the percentage of subjects with ,1 unhealed lesion. Results, In all, 108 subjects completed the study. Naproxen impaired antral lesion healing more than placebo, clopidogrel, aspirin or celecoxib (mean injury score of 4.3 vs. 3.0, 2.7, 3.2, and 3.2, respectively, P < 0.05). Naproxen impaired duodenal lesion healing more than placebo, clopidogrel or aspirin (mean injury score of 4.0 vs. 2.4, 2.6, and 2.2, respectively, P < 0.05). More subjects taking naproxen than placebo or clopidogrel had ,1 unhealed antral lesions (72.2% vs. 36.0% and 32.0%, respectively, P < 0.05) and unhealed duodenal lesions (61.1% vs. 16.0% and 28.0%, respectively, P < 0.05). Conclusions, Naproxen may impair gastroduodenal healing more than aspirin or celecoxib in H. pylori negative subjects. Clopidogrel did not impair mucosal healing. [source] | ||||||||||||||||||||||||||||||||||||||||