-
Chemosphere Apr 2022Water pollution poses an important problem, but limited information is available about the joined effects of xenobiotics of different chemical groups to evaluate the...
Water pollution poses an important problem, but limited information is available about the joined effects of xenobiotics of different chemical groups to evaluate the real biological response. Procambarus clarkii (P. clarkii) has been demonstrated to be a good bioindicator for assessing the quality of aquatic ecosystems. In this work, we studied the bioaccumulation of cadmium (Cd), arsenic (As) and diclofenac (DCF) in different tissues of P. clarkii during 21 days after the exposure to a "chemical cocktail" of As, Cd and DCF, and until 28 days considering a depuration period. In addition, a combined untargeted and targeted metabolomic analysis was carried out to delve the metabolic impairments caused as well as the metabolization of DCF. Our results indicate that As and Cd were mainly accumulated in the hepatopancreas followed by gills and finally abdominal muscle. As and Cd show a general trend to increase the concentration throughout the exposure experience, while a decrease in the concentration of these elements is observed after 7 days of the depuration process. This is also the case in the abdominal muscle for Cd, but not for As and DCF, which increased the concentration in this tissue in the depuration phase. The hepatopancreas showed the greatest number of metabolic pathways affected. Thus, we observed a crucial bioaccumulation of xenobiotics and impairments of metabolites in different tissues. This is the first study combining the exposure to metals and pharmaceutically active compounds in P. clarkii by untargeted metabolomics including the biotransformation of DCF.
Topics: Animals; Astacoidea; Diclofenac; Ecosystem; Metabolomics; Metals, Heavy; Water Pollutants, Chemical
PubMed: 34968517
DOI: 10.1016/j.chemosphere.2021.133410 -
The Cochrane Database of Systematic... Oct 2007Lumiracoxib is a novel selective cyclooxygenase-2 (COX-2) inhibitor. COX-2 inhibitors have been developed to avoid COX-1 related gastrointestinal (GI) problems.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lumiracoxib is a novel selective cyclooxygenase-2 (COX-2) inhibitor. COX-2 inhibitors have been developed to avoid COX-1 related gastrointestinal (GI) problems. Lumiracoxib has analgesic and anti-inflammatory activity comparable with traditional non-steroidal anti-inflammatory drugs (tNSAIDs) in the management of post-operative pain, but with the advantage of better GI tolerability.
OBJECTIVES
To review the analgesic efficacy, duration of analgesia, and adverse effects of a single oral dose of lumiracoxib for moderate to severe postoperative pain in adults and compare it with established analgesics.
SEARCH STRATEGY
We searched CENTRAL (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to March 2007), EMBASE (1974 to 2006), and PubMed (February 2007).
SELECTION CRITERIA
Single oral dose, randomised placebo controlled trials of lumiracoxib, in acute postoperative pain, in adult patients.
DATA COLLECTION AND ANALYSIS
Trials were quality scored and data extracted by two review authors independently. Summed pain relief (TOTPAR) was extracted and converted into dichotomous information yielding the number of patients with at least 50% pain relief. These derived results were used to calculate the relative benefit (RB) and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief.
MAIN RESULTS
Three studies (737 patients) met the inclusion criteria. In total 211 patients were treated with lumiracoxib 400 mg, 51 with lumiracoxib 100 mg, and 161 with placebo. Active comparators were naproxen 500 mg (60 patients), rofecoxib 50 mg (102), celecoxib 200 mg (101), and ibuprofen 400 mg (51). One hundred patients (48%) given lumiracoxib 400 mg had at least 50% pain relief over six hours, compared with 17 (11%) given placebo; RB 4.8 (95% CI 2.9 to 7.9), NNT 2.7 (2.2 to 3.5). Weighted median time to use of rescue medication was 7.4 hours for lumiracoxib 400 mg and 1.8 hours for placebo. Patient global assessment at study endpoint was rated as "excellent" by 71 patients (34%) given lumiracoxib 400 mg and 5 (3%) given placebo. Median time to onset of analgesia was shorter for lumiracoxib 400 mg (0.6 to 1.5 hours) than placebo (>12 hours), and use of rescue medication within 12 hours occurred in 64 patients (58%) given lumiracoxib 400 mg and 100 (91%) given placebo. Adverse events reported were generally mild to moderate in severity, with one serious adverse event reported in a patient given placebo.
AUTHORS' CONCLUSIONS
Lumiracoxib 400 mg given as a single oral dose, is an effective analgesic for acute postoperative pain.
Topics: Administration, Oral; Cyclooxygenase 2 Inhibitors; Diclofenac; Humans; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 17943921
DOI: 10.1002/14651858.CD006865 -
PloS One 2016Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the...
Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats.
Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and L-NAME. BPC 157 completely ameliorated symptoms in massive intestinal resection-, massive intestinal resection plus diclofenac-, and massive intestinal resection plus diclofenac plus L-NAME-treated short bowel rats that presented with cyclooxygenase (COX)-NO-system inhibition. L-arginine ameliorated only L-NAME-induced aggravation of symptoms in rats subjected to massive intestinal resection and administered diclofenac plus L-NAME.
Topics: Anastomosis, Surgical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arginine; Brain; Diclofenac; Gastrointestinal Tract; Intestine, Small; Liver; Male; NG-Nitroarginine Methyl Ester; Peptide Fragments; Proteins; Rats; Rats, Wistar; Wound Healing
PubMed: 27627764
DOI: 10.1371/journal.pone.0162590 -
Biomedicine & Pharmacotherapy =... Mar 2019Topical formulations of non-steroidal anti-inflammatory drugs are often used to provide effective local drug concentration while limiting systemic exposure and...
Topical formulations of non-steroidal anti-inflammatory drugs are often used to provide effective local drug concentration while limiting systemic exposure and associated adverse events. Formulation composition has great influence on the rate of transdermal drug transport through human skin. This study was performed to compare the ex vivo transdermal transport of diclofenac from three topical formulations, a 1% liposomal gel formulation of diclofenac sodium and two emulsion gel formulations, 1.16% and 2.32% diclofenac diethylamine (equivalent to 1% and 2% diclofenac sodium). Human skin was obtained during unrelated surgical procedures and frozen at -20 °C until use. Three skin specimens were thawed, prepared for testing, and placed in a Franz cell with the stratum corneum facing the donor compartment. About 200 μl of each formulation was placed on the skin, and the receptor compartment fluid (phosphate buffered saline, pH 7.4, 32 °C) was sampled over the next 48 h. Diclofenac concentration was measured with a validated HPLC method. The transdermal permeability coefficient for the liposome 1% gel was 69.3 ± 14.4 10 cm•s, compared with 34.9 ± 9.1 10 cm•s (P = 0.001) and 47.1±9.5 10 cm•s (P = 0.005) for the emulsion gel 1.16% and emulsion gel 2.32%, respectively. A statistically significant difference between transdermal transport of diclofenac from the liposome gel 1% and the emulsion gel 1.16% was evident after 9 h, a clinically relevant result because these products are typically applied 2 to 4 times daily. Based on these observations, liposome gel 1% formulation of diclofenac may have a clinical advantage compared with the emulsion gel 1.16% formulation.
Topics: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug Compounding; Gels; Humans; Liposomes; Organ Culture Techniques; Skin; Skin Absorption
PubMed: 30612003
DOI: 10.1016/j.biopha.2018.12.079 -
Journal of Hazardous Materials Aug 2023The use of unicellular algae to remove xenobiotics (including drugs) from wastewaters is one of the rapidly developing areas of environmental protection. Numerous data...
The use of unicellular algae to remove xenobiotics (including drugs) from wastewaters is one of the rapidly developing areas of environmental protection. Numerous data indicate that for efficient phycoremediation three processes are important, i.e. biosorption, bioaccumulation, and biotransformation. Although biosorption and bioaccumulation do not raise any serious doubts, biotransformation is more problematic since its products can be potentially more toxic than the parent compounds posing a threat to organisms living in a given environment, including organisms that made this transformation. Thus, two questions need to be answered before the proper algae strain is chosen for phycoremediation, namely what metabolites are produced during biotransformation, and how resistant is the analyzed strain to a mixture of parent compound and metabolites that appear over the course of culture? In this work, we evaluated the remediation potential of the model green alga Chlamydomonas reinhardtii in relation to non-steroidal anti-inflammatory drugs (NSAIDs), as exemplified by diclofenac. To achieve this, we analysed the susceptibility of C. reinhardtii to diclofenac as well as its capability to biosorption, bioaccumulation, and biotransformation of the drug. We have found that even at a relatively high concentration of diclofenac the algae maintained their vitality and were able to remove (37.7%) DCF from the environment. A wide range of phase I and II metabolites of diclofenac (38 transformation products) was discovered, with many of them characteristic rather for animal and bacterial biochemical pathways than for plant metabolism. Due to such a large number of detected products, 18 of which were not previously reported, the proposed scheme of diclofenac transformation by C. reinhardtii not only significantly contributes to broadening the knowledge in this field, but also allows to suggest possible pathways of degradation of xenobiotics with a similar structure. It is worth pointing out that a decrease in the level of diclofenac in the media observed in this study cannot be fully explained by biotransformation (8.4%). The mass balance analysis indicates that other processes (total 22%), such as biosorption, a non-extractable residue formation, or complete decomposition in metabolic cycles can be involved in the diclofenac disappearance, and those findings open the prospects of further research.
Topics: Animals; Diclofenac; Chlamydomonas reinhardtii; Anti-Inflammatory Agents, Non-Steroidal; Biotransformation; Water; Water Pollutants, Chemical
PubMed: 37163898
DOI: 10.1016/j.jhazmat.2023.131570 -
Environmental Pollution (Barking, Essex... Jun 2016Pharmaceuticals can enter the soil environment when animal slurries and sewage sludge are applied to land as a fertiliser or during irrigation with contaminated water....
Pharmaceuticals can enter the soil environment when animal slurries and sewage sludge are applied to land as a fertiliser or during irrigation with contaminated water. These pharmaceuticals may then be taken up by soil organisms possibly resulting in toxic effects and/or exposure of organisms higher up the food chain. This study investigated the influence of soil properties on the uptake and depuration of pharmaceuticals (carbamazepine, diclofenac, fluoxetine and orlistat) in the earthworm Eisenia fetida. The uptake and accumulation of pharmaceuticals into E. fetida changed depending on soil type. Orlistat exhibited the highest pore water based bioconcentration factors (BCFs) and displayed the largest differences between soil types with BCFs ranging between 30.5 and 115.9. For carbamazepine, diclofenac and fluoxetine BCFs ranged between 1.1 and 1.6, 7.0 and 69.6 and 14.1 and 20.4 respectively. Additional analysis demonstrated that in certain treatments the presence of these chemicals in the soil matrices changed the soil pH over time, with a statistically significant pH difference to control samples. The internal pH of E. fetida also changed as a result of incubation in pharmaceutically spiked soil, in comparison to the control earthworms. These results demonstrate that a combination of soil properties and pharmaceutical physico-chemical properties are important in terms of predicting pharmaceutical uptake in terrestrial systems and that pharmaceuticals can modify soil and internal earthworm chemistry which may hold wider implications for risk assessment.
Topics: Animals; Carbamazepine; Diclofenac; Fluoxetine; Hydrogen-Ion Concentration; Lactones; Oligochaeta; Orlistat; Pharmaceutical Preparations; Soil; Soil Pollutants; Water
PubMed: 27049789
DOI: 10.1016/j.envpol.2016.03.044 -
Drug Discoveries & Therapeutics Nov 2022The aim of this study was to evaluate patient satisfaction and usability scores of different tape treatments and examine the scores in relation to the mechanical...
The aim of this study was to evaluate patient satisfaction and usability scores of different tape treatments and examine the scores in relation to the mechanical characteristics of the tape formulation. A questionnaire for the assessment of comfort level and satisfaction with two brand-name (Naboal, Voltaren) and four generic tapes (Yutoku, Teikoku, Rakool, Towa) containing sodium diclofenac was developed and then applied to 12 healthy volunteers. Results showed that Voltaren was difficult to apply to the skin and easier to peel off the skin than Naboal (p < 0.01). Moreover, Rakool was easier to peel than Naboal (p < 0.05). The mechanically measured peeling force was associated with pain during peeling off (r = -0.65), and the measured value of bending rigidity was associated with ease of peeling off (r = -0.97). The knowledge obtained regarding the influence of pharmaceutical properties on the degree of satisfaction with and usability of different tape formulations may be useful for supporting the selection of generic tapes tailored to individual needs or pharmacist preferences, and thus improve treatment adherence and clinical outcomes.
Topics: Humans; Diclofenac; Patient Selection; Drugs, Generic; Surveys and Questionnaires; Pharmacists
PubMed: 36261340
DOI: 10.5582/ddt.2022.01071 -
The Cochrane Database of Systematic... Sep 2012Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly taken orally, but they are also available in topical preparations to be applied to or rubbed onto the skin of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly taken orally, but they are also available in topical preparations to be applied to or rubbed onto the skin of a painful joint, typically one affected by arthritis, with the aim of relieving pain locally. Topical NSAIDs are widely used in some parts of the world for acute and chronic painful conditions, but have not been universally accepted until recently. One of the problems has been that older clinical studies were generally short, lasting four weeks or less, and short duration studies are not regarded as adequate in ongoing painful conditions.
OBJECTIVES
To examine the use of topical NSAIDs in chronic musculoskeletal pain, focusing on studies of high methodological quality, and examining the measured effect of the preparations according to study duration. The principal aim was to estimate treatment efficacy in longer duration studies of at least 8 weeks.
SEARCH METHODS
A series of electronic searches, together with bibliographic searches, and searches of in-house databases were combined with electronic searches of clinical trial registers and manufacturers of topical NSAIDs, or companies known to be actively researching topical NSAIDs. There had to be at least 10 participants in each treatment arm, with application of treatment at least once daily.
SELECTION CRITERIA
Randomised, double blind studies with placebo or active comparators, where at least one treatment was a topical NSAID product, in any topical formulation (cream, gel, patch, solution), in studies lasting at least two weeks.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study quality and validity, and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk (RR) and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment.
MAIN RESULTS
Information was available from 7688 participants in 34 studies from 32 publications; 23 studies compared a topical NSAID with placebo. Topical NSAIDs were significantly more effective than placebo for reducing pain due to chronic musculoskeletal conditions. The best data were for topical diclofenac in osteoarthritis, where the NNT for at least 50% pain relief over 8 to 12 weeks compared with placebo was 6.4 for the solution, and 11 for the gel formulation. There were too few data of good quality to calculate NNTs for other individual topical NSAIDs compared with placebo. Direct comparison of topical NSAID with an oral NSAID did not show any difference in efficacy. There was an increase in local adverse events (mostly mild skin reactions) with topical NSAIDs compared with placebo or oral NSAIDs, but no increase in serious adverse events. Gastrointestinal adverse events with topical NSAID did not differ from placebo, but were less frequent than with oral NSAIDs.A substantial amount of data from unpublished studies was unavailable. Much of this probably relates to formulations that have never been marketed.
AUTHORS' CONCLUSIONS
Topical NSAIDs can provide good levels of pain relief; topical diclofenac solution is equivalent to that of oral NSAIDs in knee and hand osteoarthritis, but there is no evidence for other chronic painful conditions. Formulation can influence efficacy. The incidence of local adverse events is increased with topical NSAIDs, but gastrointestinal adverse events are reduced compared with oral NSAIDs.
Topics: Administration, Topical; Adult; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Diclofenac; Humans; Musculoskeletal Pain; Randomized Controlled Trials as Topic
PubMed: 22972108
DOI: 10.1002/14651858.CD007400.pub2 -
The Cochrane Database of Systematic... Jul 2009Aceclofenac is the prodrug of the non-steroidal anti-inflammatory drug (NSAID) diclofenac, widely used to treat acute and chronic pain. There are no known systematic... (Review)
Review
BACKGROUND
Aceclofenac is the prodrug of the non-steroidal anti-inflammatory drug (NSAID) diclofenac, widely used to treat acute and chronic pain. There are no known systematic reviews of its analgesic efficacy in acute postoperative pain. This review sought to evaluate the efficacy and safety of oral aceclofenac in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties.
OBJECTIVES
To assess the efficacy of single dose oral aceclofenac in acute postoperative pain, and any associated adverse events.
SEARCH STRATEGY
We searched The Cochrane Library (Issue 1, 2009), MEDLINE via Ovid (1966 to March 2009); EMBASE via Ovid (1980 to March 2009); the Oxford Pain Relief Database (1950 to 1994); and reference lists of articles.
SELECTION CRITERIA
Randomised, double-blind, placebo-controlled clinical trials of oral aceclofenac for relief of acute postoperative pain in adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. The area under the "pain relief versus time" curve was used to derive the proportion of participants with paracetamol plus codeine and placebo or paracetamol alone experiencing least 50% pain relief over 4 to 6 hours, using validated equations. The number needed to treat to benefit (NNT) was calculated using 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals was also collected.
MAIN RESULTS
Searches identified only one study (217 participants total), which used oral aceclofenac 150 mg in patients with established postoperative pain. Aceclofenac 150 mg could not be distinguished from placebo, though ibuprofen 400 mg was distinguished from placebo.
AUTHORS' CONCLUSIONS
In the absence of evidence of efficacy for oral aceclofenac in acute postoperative pain (at least at 150 mg single dose), its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies are lacking, use in other indications should be evaluated carefully. Given the large number of effective drugs available in this and similar classes of analgesics, there is no urgent research agenda required to demonstrate the effective dose of aceclofenac in acute postoperative pain.
Topics: Acute Disease; Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans; Pain, Postoperative
PubMed: 19588436
DOI: 10.1002/14651858.CD007588.pub2 -
Journal of Pharmacy & Pharmaceutical... 2009There is evidence that the sulfonylurea antidiabetic agent glibenclamide reduces the analgesic action of non-steroidal anti-inflammatory drugs (NSAIDs), opioids and...
PURPOSE
There is evidence that the sulfonylurea antidiabetic agent glibenclamide reduces the analgesic action of non-steroidal anti-inflammatory drugs (NSAIDs), opioids and neuromodulators in animal models. Therefore, in view of the vast clinical uses and interactions of NSAIDs with commonly used therapeutic agents, the interaction of the NSAID diclofenac and glibenclamide was investigated about pharmacokinetic profile and antinociceptive effect in rats.
METHODS
Antinociception was assessed using the formalin test. Fifty microliters of diluted formalin was injected s.c. into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection. Rats were treated with oral administration of vehicle or increasing doses of diclofenac (3-18 mg/kg) before formalin injection. To determine the pharmacodynamic interaction between diclofenac and glibenclamide, the effect of oral administration of glibenclamide (1-30 mg/kg) on the antinociceptive effect induced by diclofenac (18 mg/kg, p.o.) was assessed. To evaluate the pharmacokinetic interaction between diclofenac and glibenclamide, the effect of glibenclamide (10 mg/kg, p.o.) on the pharmacokinetic of diclofenac (18 mg/kg, p.o.) was studied in the rat. Blood samples were taken over 8 h and analyzed using a validated high-performance liquid chromatography method to generate the pharmacokinetic profile of diclofenac. Pharmacokinetic parameters were estimated using noncompartmental analysis.
RESULTS
Systemic administration of diclofenac produced a dose-dependent antinociceptive effect in the formalin test. Systemic treatment with glibenclamide prevented diclofenac-induced antinociception. In pharmacokinetic interaction study, no significant (P>0.05) change in diclofenac concentration-time profiles in the presence of glibenclamide was detected.
CONCLUSION
The experimental findings suggest that systemic glibenclamide is able to block the diclofenac-induced antinociception in the rat formalin test. Besides, this antagonism was not produced by diminution in the bioavailability of diclofenac. Likewise, the validated assay had sufficient accuracy and precision for pharmacokinetic determination of diclofenac in the rat.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, High Pressure Liquid; Diclofenac; Dose-Response Relationship, Drug; Drug Interactions; Female; Glyburide; Hypoglycemic Agents; KATP Channels; Limit of Detection; Pain; Pain Measurement; Potassium Channel Blockers; Rats; Rats, Wistar
PubMed: 20067705
DOI: 10.18433/j3s597