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Pain Research & Management 2018We compared the efficacy of diclofenac potassium in unpublished clinical study reports (CSRs) and published reports to examine publication bias, industry bias, and... (Review)
Review
We compared the efficacy of diclofenac potassium in unpublished clinical study reports (CSRs) and published reports to examine publication bias, industry bias, and comprehensiveness. Novartis provided CSRs of randomised double-blind trials of diclofenac potassium involving postoperative patients following third molar extraction (3 trials, =519), gynaecological surgery (3 trials, =679), and dysmenorrhoea (2 trials, =711) conducted in 1988-1990. Searches identified published reports of 6 trials. Information from 599/1909 patients was not published; trials with 846/1909 patients were published in a defunct journal. Greater methodological information in CSRs contributed to lesser risk of bias than published trials. Numbers needed to treat (NNT) from CSRs for all six postoperative trials for at least 50% of maximum pain relief over 6 h were 2.2 (95% confidence interval, 1.9-2.6) and 2.1 (1.8-2.4) for 50 and 100 mg diclofenac potassium, respectively. A Cochrane review of published trial data reported NNTs of 2.1 and 1.9, and one comprehensive analysis reported NNTs of 2.2 and 2.1, respectively. All analyses had similar results for patients remedicating within 8 h. No data from dysmenorrhoea CSRs appeared in a Cochrane review. CSRs provide useful information and increase confidence. Stable efficacy estimates with standard study designs reduce the need for updating reviews.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Diclofenac; Dysmenorrhea; Female; Humans; Male; Pain, Postoperative
PubMed: 29623148
DOI: 10.1155/2018/9493413 -
Archives of Razi Institute Apr 2022The liver and kidney are the most important organs in the body, and they both act as target structures for drug-induced injury as a consequence of their functions in...
The liver and kidney are the most important organs in the body, and they both act as target structures for drug-induced injury as a consequence of their functions in metabolisms, detoxifications, storage, elimination of medications, and their metabolites. The present study aimed to examine the role of the natural and free radical scavenger "CoQ10" against diclofenac-induced hepatic and renal tissue injury. In total, 36 adult Wistar rats were randomly divided into three equal groups (n=12). The animals in the control group did not receive any medication or treatments, and the second group included animals that received intramuscular (IM) injection of Diclofenac (DF) (at a dose of 10 mg/kg once daily for 14 days). Moreover, the third group was given the IM injection of DF (at a dose of 10 mg/kg once daily for 14 days) +CoQ10. After 14 days, DF prompted signified hepatic and renal injury indicated by elevated biochemical parameters, such as total serum bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, and uric acid, compared to the control and the third group. However, the group that received Diclofenac+CoQ10 had significantly lower hepatic and renal dysfunctions, compared to the second treated group. DF toxic effects could be the consequences of mitochondrial dysfunction and free radical effects. Remarkably, therapeutic supplementation of CoQ10 diminished the DF-induced toxic oxidative injury and apoptotic cell death. The protective effects of CoQ10 were attributed to its antioxidants and free radical scavenger activity.
Topics: Rats; Animals; Diclofenac; Alanine Transaminase; Free Radical Scavengers; Creatinine; Uric Acid; Alkaline Phosphatase; Rats, Wistar; Aspartate Aminotransferases; Bilirubin
PubMed: 36284948
DOI: 10.22092/ARI.2022.357210.1998 -
Basic & Clinical Pharmacology &... Apr 2022Several studies investigated diclofenac tissue concentrations using microdialysis (MD). However, thorough evaluations of the optimal MD set-up for diclofenac are...
Several studies investigated diclofenac tissue concentrations using microdialysis (MD). However, thorough evaluations of the optimal MD set-up for diclofenac are unavailable. Thus, this in vitro MD study aimed to compare different set-ups to improve quantitative recovery of diclofenac. In forward and reverse in vitro MD experiments with diclofenac at two concentrations (1 and 100 ng/ml), the perfusion solutions physiological saline 0.9% (PS) and human albumin 1% (HSA) were compared using tissue probes (10-mm membrane) and customized intravenous (iv) probes (30-mm membrane). Using PS, the mean relative recovery of diclofenac at 1 ng/ml was 1.6% ± 0.04% and 3.12% ± 0.00% with the tissue probe and the iv probe, respectively. The respective mean relative recovery for diclofenac at 100 ng/ml was 0.02% ± 0.01% and 0.21% ± 0.11%. Using HSA, the mean relative recovery was 314% ± 25% (tissue probe) and 1064% ± 97% (iv probe) for diclofenac at 1 ng/ml and 444% ± 91% and 1415% ± 217% for diclofenac at 100 ng/ml. In reverse dialysis using PS, the mean relative loss of diclofenac was 99.2% ± 0.5% (tissue probe) and 95.8% ± 1.7% (iv probe). Using HSA, the mean relative loss was -4.4% ± 7.2% and 0.2% ± 7.5%, respectively. PS and HSA were not suitable perfusion solutions for quantification of absolute diclofenac concentrations. Despite methodological challenges, HSA may be used for comparative experiments or bioequivalence studies.
Topics: Administration, Cutaneous; Diclofenac; Humans; Microdialysis; Perfusion
PubMed: 35048557
DOI: 10.1111/bcpt.13709 -
Drug Metabolism and Pharmacokinetics Dec 2021Cisplatin (CDDP) is a well-known anticancer agent, and CDDP-induced nephrotoxicity (CIN) is one of the most serious adverse effects. Previously, we revealed that while...
Diclofenac potentiates the antitumor effect of cisplatin in a xenograft mouse model transplanted with cisplatin-resistant cells without enhancing cisplatin-induced nephrotoxicity.
Cisplatin (CDDP) is a well-known anticancer agent, and CDDP-induced nephrotoxicity (CIN) is one of the most serious adverse effects. Previously, we revealed that while celecoxib reduces CIN, diclofenac does not appear to enhance it. Furthermore, we reported that diclofenac additively enhances the cytotoxic effect of CDDP on CDDP-resistant A549 cells (A549/DDP cells) and their spheroids. In addition, celecoxib reduces the cytotoxic effect of CDDP on A549/DDP cells while demonstrating an anticancer effect; however, it enhanced the effect of CDDP cytotoxicity on spheroids. Therefore, we evaluated the effects of diclofenac or celecoxib on CIN and the antitumor effect of CDDP in a xenograft mouse model transplanted with A549/DDP cells. Although CDDP did not decrease tumor size and tumor weight, these parameters were significantly reduced following co-administration with diclofenac when compared with the control group. Conversely, celecoxib marginally suppressed the antitumor effect of CDDP. Moreover, CDDP increased the mRNA levels of kidney injury molecule 1 (Kim-1), a renal disorder marker, in the kidneys of xenograft mice; treatment with celecoxib and diclofenac did not impact Kim-1 mRNA levels increased by CDDP. In conclusion, diclofenac potentiated the antitumor effect of CDDP without enhancing CIN.
Topics: A549 Cells; Animals; Antineoplastic Agents; Cisplatin; Diclofenac; Heterografts; Humans; Mice
PubMed: 34619549
DOI: 10.1016/j.dmpk.2021.100417 -
Experimental Gerontology Jul 2023Nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, belong to the most prescribed analgesic medication after traumatic injuries. However, there is...
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, belong to the most prescribed analgesic medication after traumatic injuries. However, there is accumulating evidence that NSAIDs impair fracture healing. Because bone regeneration in aged patients is subject to significant changes in cell differentiation and proliferation as well as a markedly altered pharmacological action of drugs, we herein analyzed the effects of diclofenac on bone healing in aged mice using a stable closed femoral facture model. Thirty-three mice (male n = 14, female n = 19) received a daily intraperitoneal injection of diclofenac (5 mg/kg body weight). Vehicle-treated mice (n = 29; male n = 13, female n = 16) served as controls. Fractured mice femora were analyzed by means of X-ray, biomechanics, micro computed tomography (μCT), histology and Western blotting. Biomechanical analyses revealed a significantly reduced bending stiffness in diclofenac-treated animals at 5 weeks after fracture when compared to vehicle-treated controls. Moreover, the callus tissue in diclofenac-treated aged animals exhibited a significantly reduced amount of bone tissue and higher amounts of fibrous tissue. Further histological analyses demonstrated less lamellar bone after diclofenac treatment, indicating a delay in callus remodeling. This was associated with a decreased number of osteoclasts and an increased expression of osteoprotegerin (OPG) during the early phase of fracture healing. These findings indicate that diclofenac delays fracture healing in aged mice by affecting osteogenic growth factor expression and bone formation as well as osteoclast activity and callus remodeling.
Topics: Mice; Male; Female; Animals; Diclofenac; Fracture Healing; Anti-Inflammatory Agents, Non-Steroidal; X-Ray Microtomography; Bony Callus; Femoral Fractures; Biomechanical Phenomena
PubMed: 37169100
DOI: 10.1016/j.exger.2023.112201 -
Molecules (Basel, Switzerland) May 2022Self-assembly of organic ions in aqueous solutions is a hot topic at the present time, and substances that are well-soluble in water are usually studied. In this work,...
Self-assembly of organic ions in aqueous solutions is a hot topic at the present time, and substances that are well-soluble in water are usually studied. In this work, aqueous solutions of sodium diclofenac are investigated, which, like most medicinal compounds, is poorly soluble in water. Classical MD modeling of an aqueous solution of diclofenac sodium showed equilibrium between the hydrated anion and the hydrated dimer of the diclofenac anion. The assignment and interpretation of the bands in the UV, NIR, and IR spectra are based on DFT calculations in the discrete-continuum approximation. It has been shown that the combined use of spectroscopic methods in various frequency ranges with classical MD simulations and DFT calculations provides valuable information on the association processes of medical compounds in aqueous solutions. Additionally, such a combined application of experimental and calculation methods allowed us to put forward a hypothesis about the mechanism of the effect of diclofenac sodium in high dilutions on a solution of diclofenac sodium.
Topics: Anions; Diclofenac; Ions; Solutions; Water
PubMed: 35630826
DOI: 10.3390/molecules27103350 -
Molecules (Basel, Switzerland) Aug 2023Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) from the group of phenylacetic acid derivatives, which has analgesic, anti-inflammatory and antipyretic...
Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) from the group of phenylacetic acid derivatives, which has analgesic, anti-inflammatory and antipyretic properties. The interaction of non-steroidal anti-inflammatory drugs with cell membranes can affect their physicochemical properties, which, in turn, can cause a number of side effects in the use of these drugs. Electron paramagnetic resonance (EPR) spectroscopy could be used to study the interaction of diclofenac with a membrane, if its spin-labeled analogs existed. This paper describes the synthesis of spin-labeled diclofenac (diclofenac-SL), which consists of a simple sequence of transformations such as iodination, esterification, Sonogashira cross-coupling, oxidation and saponification. EPR spectra showed that diclofenac-SL binds to a lipid membrane composed of palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). H electron spin echo spectroscopy (ESEEM) was used to determine the position of the diclofenac-SL relative to the membrane surface. It was established that its average depth of immersion corresponds to the 5th position of the carbon atom in the lipid chain.
Topics: Diclofenac; Spin Labels; Anti-Inflammatory Agents, Non-Steroidal; Membranes; Glycerylphosphorylcholine
PubMed: 37630243
DOI: 10.3390/molecules28165991 -
International Journal of Environmental... Jul 2021In the present research, the effect of two hybrid treatments, ozone followed by powdered activated carbon (PAC) or PAC followed by ozone (O), was studied for the removal...
In the present research, the effect of two hybrid treatments, ozone followed by powdered activated carbon (PAC) or PAC followed by ozone (O), was studied for the removal of two drugs present in water: diclofenac and carbamazepine. In the study, two initial concentrations of each of the contaminants, 0.7 mg L and 1.8 mg L, were used. Different doses of PAC between 4-20 mg L were studied as variables, as well as different doses of O between 0.056-0.280 mg L. The evolution of the concentration of each contaminant over time was evaluated. From the results obtained, it was concluded that the combined treatment with ozone followed by PAC reduces between 50% and 75% the time required to achieve 90% removal of diclofenac when compared with the time required when only activated carbon was used. In the case of carbamazepine, the time required was 97% less. For carbamazepine, to achieve reduction percentages of up to 90%, O treatment followed by PAC acted faster than PAC followed by O. In the case of diclofenac, PAC treatment followed by O was faster to reach concentrations of up to 90%. However, to reach yields below 80%, O treatment followed by PAC was more efficient.
Topics: Adsorption; Carbamazepine; Charcoal; Diclofenac; Waste Disposal, Fluid; Water Pollutants, Chemical; Water Purification
PubMed: 34281100
DOI: 10.3390/ijerph18137163 -
Asian Pacific Journal of Cancer... Apr 2022To examine the effects of ibuprofen, naproxen and diclofenac, non-steroidal anti-inflammatory drugs (NSAIDs) on cell proliferation activity of the human CCA cell lines.
OBJECTIVE
To examine the effects of ibuprofen, naproxen and diclofenac, non-steroidal anti-inflammatory drugs (NSAIDs) on cell proliferation activity of the human CCA cell lines.
METHODS
KKU-M139 and KKU-213B cell lines were used in this study. The cell viability was assessed by the MTT assay. Lipid synthesis determined by Oil red O staining and colorimetric assay. An inverted phase-contrast light microscope was used to investigate the histological change of the cells. Caspases 3/7 activity and AnnexinV/PI were used to assess apoptosis by multiple microplate reader.
RESULTS
The results showed that ibuprofen, naproxen and diclofenac suppressed the viability of the KKU-M139 and KKU-213B cells in a dose-dependent manner, as measured especially diclofenac. However, these three NSAIDs slightly decreased lipid synthesis determined by Oil red O staining and colorimetric assay. The histological change observations showed the shrinking cell and become star-shaped in high dose treated groups. Interestingly, these NSAIDs exhibited in both of KKU-M139 and KKU-213B cell lines, the diclofenac-treated cells had the most injury cells. The cells exhibited cell injury features. In addition, the detection of caspase 3/7 and AnnexinV/PI in this investigation revealed early cell apoptotic characteristics.
CONCLUSION
These finding suggest that ibuprofen, naproxen and diclofenac suppress cell viability. The results reveal that ibuprofen, naproxen and diclofenac, which induce the histological change and apoptosis. This study indicates that these NSAIDs may be used as an anti-proliferation agent for the treatment of CCA in the future.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cell Line, Tumor; Cell Proliferation; Cholangiocarcinoma; Diclofenac; Humans; Ibuprofen; Lipids; Naproxen
PubMed: 35485696
DOI: 10.31557/APJCP.2022.23.4.1351 -
Annals of Palliative Medicine Feb 2021Acute pancreatitis is an important complication of endoscopic retrograde cholangiography (ERC), occurring between 1-10% of patients. Several randomized controlled trials...
BACKGROUND
Acute pancreatitis is an important complication of endoscopic retrograde cholangiography (ERC), occurring between 1-10% of patients. Several randomized controlled trials and meta-analyses have demonstrated the effectiveness of nonsteroidal anti-inflammatories (NSAIDs) such as diclofenac and indomethacin as a post-ERC pancreatitis (PEP) prophylaxis. The aim is to determine if the rectal diclofenac use reduces the PEP rate.
METHODS
Retrospective cohort study. Subjects were included who underwent ERC for different indications in a tertiary center between January 2015 and June 2016. Two groups were analyzed: group A (without diclofenac use) and group B (with use of diclofenac as PEP prophylaxis). Biodemographic, technical and mortality variables were measured.
RESULTS
The total cohort was 116 patients, 67 in group A and 49 in group B. The average age was 61.9±17.8 and 58.3±15.8 years, respectively (P=0.2606). Gender distribution showed a women predominance in both groups (P=0.933). Of the technical variables measured, the precut showed a statistically significant relationship to PEP (P=0.013). Of the total cohort, 8.6% developed acute pancreatitis after an ERC: four in group A and six in group B (P=0.196). In those who developed PEP (n=10), six patients developed severe acute pancreatitis (SAP). The average hospitalization for PEP was 32.2±34 days (P=0.881). No patients died, not were there any adverse reactions to the drug.
CONCLUSIONS
Rectal diclofenac administered at the beginning of the ERC did not reduce the PEP rate in this patients cohort.
Topics: Acute Disease; Adult; Aged; Cholangiography; Cholangiopancreatography, Endoscopic Retrograde; Diclofenac; Female; Humans; Middle Aged; Pancreatitis; Retrospective Studies
PubMed: 33040554
DOI: 10.21037/apm-19-395