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The Cochrane Database of Systematic... Jul 2015Diclofenac is a nonsteroidal anti-inflammatory drug, available as a potassium salt (immediate release) or sodium salt (enteric coated to suppress dissolution in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diclofenac is a nonsteroidal anti-inflammatory drug, available as a potassium salt (immediate release) or sodium salt (enteric coated to suppress dissolution in the stomach). This review updates an earlier review published in the Cochrane Database of Systematic Reviews (Issue 2, 2009) entitled 'Single dose oral diclofenac for acute postoperative pain in adults'.
OBJECTIVES
To assess the analgesic efficacy and adverse effects of a single oral dose of diclofenac for moderate to severe postoperative pain, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of articles. The date of the most recent search was 9 March 2015.
SELECTION CRITERIA
Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently considered studies for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants with at least 50% pain relief over six hours prescribed either diclofenac or placebo. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the 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 effects.
MAIN RESULTS
This update included three new studies, providing a 26% increase in participants in comparisons between diclofenac and placebo. We included 18 studies involving 3714 participants, 1902 treated with diclofenac and 1007 with placebo. This update has also changed the focus of the review, examining the effects of formulation in more detail than previously. This is a result of increased understanding of the importance of speed of onset in determining analgesic efficacy in acute pain.The largest body of information, for diclofenac potassium 50 mg, in seven studies, produced an NNT for at least 50% of maximum pain relief compared with placebo of 2.1 (95% confidence interval (CI) 1.9 to 2.5) (high quality evidence). There was a graded improvement in efficacy as doses rose from 25 mg to 100 mg, both for participants achieving at least 50% maximum pain relief, and for remedication within 6 to 8 hours. Fast-acting formulations (dispersible products, solutions, and softgel formulations) had a similar efficacy for a 50 mg dose, with an NNT of 2.4 (2.0 to 3.0). Diclofenac sodium in a small number of studies produced a lesser effect, with an NNT of 6.6 (4.1 to 17) for the 50 mg dose.Adverse event rates were low in these single dose studies, with no difference between diclofenac and placebo (moderate quality evidence).
AUTHORS' CONCLUSIONS
Diclofenac potassium provides good pain relief at 25 mg, 50 mg, and 100 mg doses. Diclofenac sodium has limited efficacy and should probably not be used in acute pain.
Topics: Acute Pain; Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Cyclooxygenase Inhibitors; Diclofenac; Humans; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 26151766
DOI: 10.1002/14651858.CD004768.pub3 -
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 -
Archives of Toxicology Jun 2018The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In...
The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In addition, the metabolism and excretion were investigated in chimeric liver humanized and murinized FRG mice. Diclofenac reached maximum blood concentrations of 2.43 ± 0.9 µg/mL (n = 3) at 0.25 h post-dose with an AUC of 3.67 µg h/mL and an effective half-life of 0.86 h (n = 2). In the murinized animals, maximum blood concentrations were determined as 3.86 ± 2.31 µg/mL at 0.25 h post-dose with an AUC of 4.94 ± 2.93 µg h/mL and a half-life of 0.52 ± 0.03 h (n = 3). In C57BL/6J mice, mean peak blood concentrations of 2.31 ± 0.53 µg/mL were seen 0.25 h post-dose with a mean AUC of 2.10 ± 0.49 µg h/mL and a half-life of 0.51 ± 0.49 h (n = 3). Analysis of blood indicated only trace quantities of drug-related material in chimeric humanized and murinized FRG mice. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles in humanized mice were different to those of both murinized and wild-type animals, e.g., a higher proportion of the dose was detected in the form of acyl glucuronide metabolites and much reduced amounts as taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57BL/6J mice and humans revealed a greater, though not complete, match between chimeric humanized mice and humans, such that the liver humanized FRG model may represent a model for assessing the biotransformation of such compounds in humans.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Bile; Biotransformation; Chimera; Diclofenac; Feces; Half-Life; Humans; Male; Mice; Mice, Inbred C57BL; Species Specificity
PubMed: 29721588
DOI: 10.1007/s00204-018-2212-1 -
BioMed Research International 2014Osteoarthritis (OA), a common musculoskeletal disorder, is projected to affect about 60 million people of total world population by 2020. The associated pain and... (Review)
Review
Osteoarthritis (OA), a common musculoskeletal disorder, is projected to affect about 60 million people of total world population by 2020. The associated pain and disability impair the quality of life and also pose economic burden to the patient. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed in OA, while diclofenac is the most prescribed one. Oral NSAIDs are not very patient friendly, as they cause various gastrointestinal adverse effects like bleeding, ulceration, and perforation. To enhance the tolerability of diclofenac and decrease the common side effects, aceclofenac (ACE) was developed by its chemical modification. As expected, ACE is more well-tolerated than diclofenac and possesses superior efficacy but is not completely devoid of the NSAID-tagged side effects. A series of chemical modifications of already planned drug is unjustified as it consumes quanta of time, efforts, and money, and this approach will also pose stringent regulatory challenges. Therefore, it is justified to deliver ACE employing tools of drug delivery and nanotechnology to refine its safety profile. The present review highlights the constraints related to the topical delivery of ACE and the various attempts made so far for the safe and effective topical delivery employing the novel materials and methods.
Topics: Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug Delivery Systems; Inflammation; Osteoarthritis
PubMed: 25045671
DOI: 10.1155/2014/406731 -
Primary Health Care Research &... Dec 2021The most frequently prescribed analgesic drugs in primary care centers in Turkey are diclofenac and paracetamol, respectively. In this study, we aimed to compare...
INTRODUCTION
The most frequently prescribed analgesic drugs in primary care centers in Turkey are diclofenac and paracetamol, respectively. In this study, we aimed to compare paracetamol-included prescriptions (PIP) and diclofenac-included prescriptions (DIP) generated for adult patients in primary care.
METHODS
In this cross-sectional study, PIPs (n = 280 488) and DIPs (n = 337 935) created for adults by systematic sampling among primary care physicians working in Istanbul in 2016 (n = 1431) were examined. The demographic characteristics, diagnoses, and additional drugs in PIPs and DIPs were compared.
RESULTS
Women constituted the majority in both groups (69.8% and 67.9%, respectively; P < 0.05), and mean age at PIP (52.6 ± 18.8 years) was lower compared to DIP (56.3 ± 16.1 years), (P < 0.05). In single-diagnosis prescriptions, 11 of the 15 most common diagnoses in PIP were respiratory tract infections (47.9%); three pain-related diagnoses formed 4.6% of all these prescriptions. In DIP, the number of pain-related diagnoses, mostly of musculoskeletal origin, was eight (28.5%); four diagnoses (7.8%) were upper respiratory tract infections. While hypertension was the third most common diagnosis in PIP (6.1%), it was ranked first in DIP (8.0%). The percentage of prescriptions with additional analgesic (14.0% versus 18.3%, P < 0.001), proton-pump inhibitor (13.8% versus 18.4%; P < 0.001), and antihypertensive (22.0% versus 24.8%, P < 0.001) was lower in PIP compared to DIP. However, the percentage of prescriptions with antibiotics (31.3% versus 14.7%, P < 0.001) was higher in PIP.
CONCLUSION
Paracetamol appears to be preferred mostly in upper respiratory tract infections compared to the preference of diclofenac rather in painful/inflammatory musculoskeletal conditions. The presence of hypertension among the most commonly encountered diagnoses for these analgesic drugs points to challenges in establishing the diagnosing-treatment match and indicates potential irrational prescribing practice, especially for interactions.
Topics: Acetaminophen; Adult; Cross-Sectional Studies; Diclofenac; Female; Humans; Practice Patterns, Physicians'; Primary Health Care; Respiratory Tract Infections
PubMed: 34852871
DOI: 10.1017/S1463423621000797 -
Molecules (Basel, Switzerland) Feb 2022Cochlear implants, like other active implants, rely on precise and effective electrical stimulation of the target tissue but become encapsulated by different amounts of...
Cochlear implants, like other active implants, rely on precise and effective electrical stimulation of the target tissue but become encapsulated by different amounts of fibrous tissue. The current study aimed at the development of a dual drug release from a PLLA coating and from the bulk material to address short-term and long-lasting release of anti-inflammatory drugs. Inner-ear cytocompatibility of drugs was studied in vitro. A PLLA coating (containing diclofenac) of medical-grade silicone (containing 5% dexamethasone) was developed and release profiles were determined. The influence of different coating thicknesses (2.5, 5 and 10 µm) and loadings (10% and 20% diclofenac) on impedances of electrical contacts were measured with and without pulsatile electrical stimulation. Diclofenac can be applied to the inner ear at concentrations of or below 4 × 10 mol/L. Release of dexamethasone from the silicone is diminished by surface coating but not blocked. Addition of 20% diclofenac enhances the dexamethasone release again. All PLLA coatings serve as insulator. This can be overcome by using removable masking on the contacts during the coating process. Dual drug release with different kinetics can be realized by adding drug-loaded coatings to drug-loaded silicone arrays without compromising electrical stimulation.
Topics: Animals; Anti-Inflammatory Agents; Coated Materials, Biocompatible; Cochlear Implants; Dexamethasone; Diclofenac; Drug Delivery Systems; Drug Liberation; Rats; Rats, Sprague-Dawley
PubMed: 35209205
DOI: 10.3390/molecules27041417 -
Genes Jan 2023Nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids (GCs) are often used to treat articular-skeletal disorders. The extended use of NSAIDs and GCs have...
Nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids (GCs) are often used to treat articular-skeletal disorders. The extended use of NSAIDs and GCs have adverse effects on bone metabolism, reducing bone quality and impairing fracture healing. In the present study, we used mouse pre-osteoblast cells MC3T3-E1 to demonstrate the effects of diclofenac (DF) and methylprednisolone (MP) on cell proliferation and gene expression. Cells were incubated with three doses of DF or MP: 0.5 µM, 5 µM, and 50 µM. MP decreased cell viability even after 24 h, but DF inhibited cell viability after only seven days of treatment. The cells were lysed after one, two, three, and seven days of treatment, and gene expression was analyzed by reverse transcription and quantitative PCR (RT-qPCR) assays. DF did not significantly affect the expression of the osteogenic marker genes. MP modified the expression of , , and . We concluded that MP is a more potent inhibitor of mouse pre-osteoblast differentiation and viability than is DF. Our results suggest that prolonged DF treatment could be less harmful to osteoblasts than MP treatment.
Topics: Animals; Mice; Methylprednisolone; Diclofenac; Cell Differentiation; Glucocorticoids; Gene Expression; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 36672925
DOI: 10.3390/genes14010184 -
The Pan African Medical Journal 2022Artemisia is one of the important alternative treatments for many diseases, as well as the prevention of the effect of oxidizing substances that cause damage to the...
INTRODUCTION
Artemisia is one of the important alternative treatments for many diseases, as well as the prevention of the effect of oxidizing substances that cause damage to the various organs of the body, including the liver and kidneys. The kidney and the liver are considered the body's most critical organs, and their functions in storage, metabolism, detoxification and elimination of medications, and their metabolic products make them target structures for "drug-induced" harm. The goal of this investigation was to see if Artemisia extract might protect hepatic and renal tissues from diclofenac-induced damage.
METHODS
a total of 40 adult Wistar rats were separated equally into four groups randomly. The rats of the control group got only distilled water orally without medicine or therapy, while those in the second group administrated 100mg/kg/day of Artemisia orally for one month. The third group received 10mg/kg/day of Diclofenac (DF) orally. The fourth group received 10mg/kg/day of DF and 100mg/kg day of Artemisia orally. After one month, kidney parameters (albumin, creatinine, and urea) and liver parameters (aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)) were measured.
RESULTS
the results revealed increasing in the kidney (albumin, creatinine, and urea) parameters and liver parameters (AST, ALT, and ALP) in the group treated with diclofenac compared to the control group while they decreased significantly (p≤0.05) in diclofenac + Artemisia group comparing to diclofenac group.
CONCLUSION
we conclude from these results that Artemisia may have a role in reducing the toxic effect of diclofenac on kidney and liver by decreasing the liver enzymes and kidney criteria in the blood. The aim of the present study is to evaluate the role of Artemisia to reduce the toxic effect of diclofenac on liver and kidney.
Topics: Rats; Male; Animals; Diclofenac; Rats, Wistar; Artemisia; Creatinine; Plant Extracts; Liver; Kidney; Alkaline Phosphatase; Urea; Albumins
PubMed: 36942132
DOI: 10.11604/pamj.2022.43.192.36160 -
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