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General Dentistry 2017The aim of this study was to compare the efficacy and safety of transdermal and oral routes of diclofenac for postoperative pain management in patients undergoing dental... (Randomized Controlled Trial)
Randomized Controlled Trial
The aim of this study was to compare the efficacy and safety of transdermal and oral routes of diclofenac for postoperative pain management in patients undergoing dental implant placement. Twenty systemically healthy, partially edentulous patients who required dental implants bilaterally in the mandibular first molar region were included. While the patient was under local anesthesia, an implant was placed in the mandibular first molar region of one quadrant. After a minimum of 4 weeks, an implant was placed in the contralateral quadrant under local anesthesia. Patients were prescribed 50 mg of oral diclofenac, taken twice daily for 3 days, following implant placement on the first side and a 100-mg diclofenac transdermal patch, placed once daily for 3 days, after surgery on the contralateral side. Postoperative pain was documented using the Numeric Rating Scale, Verbal Rating Scale, and Pain Relief Scale. Demographic, intraoperative, and postoperative characteristics were comparable in all the patients. The data obtained with the 3 subjective scales were analyzed by the Mann-Whitney test. No statistically significant differences in scores were discerned between the oral and transdermal routes of diclofenac delivery. None of the patients developed any adverse effects when using the transdermal patch, whereas 3 patients reported gastric irritation and a mild burning sensation when taking oral diclofenac. Thus, while the efficacy of transdermal and oral diclofenac for postoperative pain management was similar, the safety of the transdermal diclofenac patches was evidently superior. Further research with larger patient samples is necessary, but delivery of diclofenac through a transdermal route is a promising approach to the management of postoperative pain.
Topics: Administration, Cutaneous; Administration, Oral; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Dental Implantation; Diclofenac; Female; Humans; Male; Middle Aged; Pain, Postoperative
PubMed: 28682286
DOI: No ID Found -
Journal of Veterinary Pharmacology and... Dec 2016The aim was to investigate diclofenac delivery into and across equine skin in vitro using Franz diffusion cells from a novel diclofenac epolamine (DIC-EP; 1.3%)...
The aim was to investigate diclofenac delivery into and across equine skin in vitro using Franz diffusion cells from a novel diclofenac epolamine (DIC-EP; 1.3%) formulation and to compare the results to those of Surpass (1% diclofenac sodium liposomal cream) and a 1% aqueous solution of diclofenac sodium. Skin was harvested from the lower legs of Freiberger geldings immediately after slaughter and sliced to a thickness of ~2 mm. Skin samples were divided into two groups [Group 1: 1 year old (n = 2) and Group 2: 6-8 years old (n = 3)]. Cumulative permeation of diclofenac in Groups 1 and 2 after 24 h using diclofenac sodium solution was 1.91 ± 0.27 and 1.76 ± 0.34 μg/cm , respectively. The values for Surpass and DIC-EP were 3.2 ± 0.8/3.3 ± 0.7 μg/cm and 230 ± 59/89.2 ± 32.5 μg/cm , respectively. Thus, diclofenac permeation from DIC-EP was significantly greater and appeared to show an age-dependent effect. Mathematical modelling showed that the DIC-EP formulation significantly increased diclofenac partitioning into the skin and a linear correlation was observed between steady-state flux and the partition parameter. Greater skin deposition of diclofenac was also observed with DIC-EP. These preliminary results suggest that the DIC-EP formulation may be effective in treating inflammatory conditions in horses.
Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Horses; Skin; Skin Physiological Phenomena
PubMed: 27030162
DOI: 10.1111/jvp.12307 -
Redox Biology Oct 2020Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with various side effects, including cardiovascular and hepatic disorders. Studies suggest...
Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with various side effects, including cardiovascular and hepatic disorders. Studies suggest that mitochondrial damage and oxidative stress are important mediators of toxicity, yet the underlying mechanisms are poorly understood. In this study, we identified that some NSAIDs, including diclofenac, inhibit autophagic flux in hepatocytes. Further detailed studies demonstrated that diclofenac induced a reactive oxygen species (ROS)-dependent increase in lysosomal pH, attenuated cathepsin activity and blocked autophagosome-lysosome fusion. The reactivation of lysosomal function by treatment with clioquinol or transfection with the transcription factor EB restored lysosomal pH and thus autophagic flux. The production of mitochondrial ROS is critical for this process since scavenging ROS reversed lysosomal dysfunction and activated autophagic flux. The compromised lysosomal activity induced by diclofenac also inhibited the fusion with and degradation of mitochondria by mitophagy. Diclofenac-induced cell death and hepatotoxicity were effectively protected by rapamycin. Thus, we demonstrated that diclofenac induces the intracellular ROS production and lysosomal dysfunction that lead to the suppression of autophagy. Impaired autophagy fails to maintain mitochondrial integrity and aggravates the cellular ROS burden, which leads to diclofenac-induced hepatotoxicity.
Topics: Autophagy; Chemical and Drug Induced Liver Injury; Diclofenac; Humans; Lysosomes; Oxidative Stress; Reactive Oxygen Species
PubMed: 33080439
DOI: 10.1016/j.redox.2020.101751 -
Turkish Journal of Medical Sciences Oct 2022In this study, we evaluate sciatic nerve injuries due to intramuscular injections, which is an important medicolegal problem frequently encountered in medical practice,...
BACKGROUND
In this study, we evaluate sciatic nerve injuries due to intramuscular injections, which is an important medicolegal problem frequently encountered in medical practice, with an extended experimental rat model of peripheral nerve injury.
METHODS
A total of 78 male Wistar albino rats were divided into five main groups, including a control group, a sham saline group, and groups that received benzathine penicillin G, diclofenac sodium, and dexamethasone, respectively. These pharmaceutical agents were applied to the sciatic nerves of all rats after exploration in the epineurial, endoneurial, and intrafascicular compartments, excluding the control group. Outcomes were evaluated for all rats and their sciatic nerves according to functional, electrophysiological, and histopathological results.
RESULTS
Injuries were most evident in the groups that received penicillin G and diclofenac sodium, and this finding was statistically significant. It was also found that endoneurial and intrafascicular injections may cause more harm than epineurial injections.
DISCUSSION
We have demonstrated that any medical injections applied to the epineurial, endoneurial, or intrafascicular compartments of the sciatic nerve may cause functional and electrophysiological loss with or without deterioration of the peripheral nerve architecture.
Topics: Male; Rats; Animals; Rats, Wistar; Peripheral Nerve Injuries; Diclofenac; Sciatic Nerve; Injections, Intramuscular
PubMed: 36422486
DOI: 10.55730/1300-0144.5499 -
Clinical Therapeutics Feb 2015This study compared the pharmacokinetic properties and safety profile of low-dose (18- and 35-mg) diclofenac capsules manufactured using SoluMatrix Fine Particle... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
This study compared the pharmacokinetic properties and safety profile of low-dose (18- and 35-mg) diclofenac capsules manufactured using SoluMatrix Fine Particle Technology (Trademark of iCeutica Inc. (Philadelphia, Pennsylvania), and the technology is licensed to Iroko Pharmaceuticals, LLC (Philadelphia, Pennsylvania) for exclusive use in NSAIDs), which produces submicron-sized drug particles with enhanced dissolution properties, to those of diclofenac potassium immediate-release (IR) 50-mg tablets.
METHODS
This Phase 1, single-center, randomized, open-label, single-dose crossover study was conducted in 40 healthy volunteers. Subjects received, in randomized order, SoluMatrix diclofenac 18- or 35-mg capsules in the fasting condition, SoluMatrix diclofenac 35-mg capsules under fed conditions, and diclofenac potassium IR 50-mg tablets under fasting and fed conditions. Pharmacokinetic parameters (T(max), C(max), AUC(0-t), AUC(0-∞)) were calculated from the concentrations of diclofenac in the plasma. Absorption, food effect, and dose proportionality were determined using a mixed-model ANOVA for C(max), AUC(0-t), AUC(0-∞). Tolerability was assessed by recording adverse events, physical examination findings, vital sign measurements: clinical laboratory test results.
FINDINGS
Overall, 35 healthy volunteers aged 18 to 52 years completed the study. The mean age of the subjects was 33.4 years, and approximately half were men (47.5%). Median T(max) values were similar between the low-dose SoluMatrix diclofenac 35-mg capsules and the diclofenac potassium IR 50-mg tablets (both, ~1.0 hour). The mean maximum plasma concentration (C(max)) after the administration of low-dose SoluMatrix diclofenac 35-mg capsules was 26% lower than that with diclofenac potassium IR 50-mg tablets under fasting conditions (868.72 vs 1194.21 ng/mL). The administration of low-dose SoluMatrix diclofenac 35-mg capsules was associated with a 23% lower overall systemic exposure compared with that of diclofenac potassium IR 50-mg tablets under fasting conditions. Food decreased the rate but not the overall extent of absorption of SoluMatrix diclofenac. No serious AEs and no clinically significant abnormalities in physical examination findings, including vital sign measurements, or clinical laboratory test results, were noted during this study.
IMPLICATIONS
The pharmacokinetic properties of low-dose SoluMatrix diclofenac capsules in the healthy volunteers in this study suggest rapid diclofenac absorption as measured by T(max). Low-dose SoluMatrix diclofenac capsules represent a potential option for the management of acute and osteoarthritis-related pain.
Topics: Adult; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Biological Availability; Capsules; Cross-Over Studies; Diclofenac; Fasting; Female; Food-Drug Interactions; Humans; Male; Middle Aged; Pennsylvania; Tablets; Young Adult
PubMed: 25499666
DOI: 10.1016/j.clinthera.2014.10.018 -
Journal of Inorganic Biochemistry Dec 2023The recently isolated Sclerotinia sclerotiorum laccase was used for the degradation of sodium diclofenac, a nonsteroidal anti-inflammatory drug widely found in the...
The recently isolated Sclerotinia sclerotiorum laccase was used for the degradation of sodium diclofenac, a nonsteroidal anti-inflammatory drug widely found in the aquatic environment. The Michaelis-Menten parameters, half-life of diclofenac at different pH values in presence of this enzyme and potential inhibitors were evaluated. Diclofenac-based radicals formed in presence of laccase were spin-trapped and detected using EPR spectroscopy. Almost complete diclofenac degradation (> 96%) occurred after a 30-h treatment via radical-based generated oligomers and their rapid precipitation, thus ensuring an unprecedented green formula suitable not only for degradation but also for straightforward removal of the degradation products. High performance liquid chromatography coupled with atmospheric pressure chemical ionization-ion trap mass spectrometry (HPLC-APCI-MS) analyses of the degradation products of diclofenac in aqueous dosage revealed the presence of at least seven products while HR Orbitrap MS analysis showed that the enzymatic treatment produced high molecular weight metabolites through a radical oligomerization mechanism of diclofenac. The enzymatically formed products precipitated and its constituting components were also characterized using UV-vis spectroscopy, infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA).
Topics: Diclofenac; Laccase; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, High Pressure Liquid
PubMed: 37844532
DOI: 10.1016/j.jinorgbio.2023.112400 -
Scientific Reports Sep 2023The formation of protein aggregates is a hallmark of many neurodegenerative diseases and systemic amyloidoses. These disorders are associated with the fibrillation of a...
The formation of protein aggregates is a hallmark of many neurodegenerative diseases and systemic amyloidoses. These disorders are associated with the fibrillation of a variety of proteins/peptides, which ultimately leads to cell toxicity and tissue damage. Understanding how amyloid aggregation occurs and developing compounds that impair this process is a major challenge in the health science community. Here, we demonstrate that pathogenic proteins associated with Alzheimer's disease, diabetes, AL/AA amyloidosis, and amyotrophic lateral sclerosis can aggregate within stress-inducible physiological amyloid-based structures, termed amyloid bodies (A-bodies). Using a limited collection of small molecule inhibitors, we found that diclofenac could repress amyloid aggregation of the β-amyloid (1-42) in a cellular setting, despite having no effect in the classic Thioflavin T (ThT) in vitro fibrillation assay. Mapping the mechanism of the diclofenac-mediated repression indicated that dysregulation of cyclooxygenases and the prostaglandin synthesis pathway was potentially responsible for this effect. Together, this work suggests that the A-body machinery may be linked to a subset of pathological amyloidosis, and highlights the utility of this model system in the identification of new small molecules that could treat these debilitating diseases.
Topics: Humans; Diclofenac; Amyloidogenic Proteins; Amyloidosis; Prostaglandin-Endoperoxide Synthases; Immunoglobulin Light-chain Amyloidosis
PubMed: 37660155
DOI: 10.1038/s41598-023-41712-2 -
Journal of Biochemical and Molecular... Oct 2017Exposure to drugs often results in toxicity in the kidney which represents the major control system maintaining homeostasis of the body and thus is especially...
Exposure to drugs often results in toxicity in the kidney which represents the major control system maintaining homeostasis of the body and thus is especially susceptible to xenobiotics. Nephrotoxicity is a life-threatening side-effect of nonsteroidal anti-inflammatory drugs (NSAIDs). Diclofenac is one of the most frequently prescribed NSAIDs and have been reported to cause multiple organs damage. Curcumin (CUR) exhibits nephroprotective properties. Therefore, rats were divided into four groups; rats of groups 3 and 4 received diclofenac (100 mg/kg, i.m.), whereas rats of groups 2 and 4 received CUR (100 mg/kg, p.o.) for 3 days. Diclofenac revealed a significant increase in urea and creatinine levels and malondialdehyde concentration and marked reduction in catalase activity and reduced glutathione concentration. Histopathologically, diclofenac produced fatty changes and eosinophilic casts were detected in the renal tubules, those were attenuated by administration of CUR prior diclofenac.
Topics: Animals; Curcumin; Diclofenac; Kidney Diseases; Kidney Tubules, Distal; Male; Rats
PubMed: 28800174
DOI: 10.1002/jbt.21951 -
Journal of Pharmaceutical Sciences Nov 2016The advances in laser technology have led to its rapidly expanding applications in dermatology. This study aims at the novel use of a non-ablative fractional laser to...
The advances in laser technology have led to its rapidly expanding applications in dermatology. This study aims at the novel use of a non-ablative fractional laser to enhance transdermal permeation of diclofenac sodium and sumatriptan succinate. The effects of the laser on skin were characterized visually with dye binding, scanning electron microscopy, pore permeability index, and histology. In vitro transdermal permeation of drugs through laser treated and untreated human dermatomed skin was analyzed over 24 h and quantified by HPLC. Drug transport through untreated skin resulted in transdermal delivery of 72.61 μg/cm ± 50.35 and 22.80 ± 0.64 μg/cm of diclofenac sodium and sumatriptan succinate, respectively. Laser treatment of skin significantly increased (p < 0.005) delivery of diclofenac sodium to 575.66 ± 207.18 μg/cm and sumatriptan succinate to 498.32 ± 97.54 μg/cm. This is a first of its kind study that demonstrates the use of 1410 nm non-ablative fractional laser to enhance transdermal permeation of 2 small molecular weight drugs.
Topics: Administration, Cutaneous; Diclofenac; Drug Delivery Systems; Electric Impedance; Humans; Laser Therapy; Organ Culture Techniques; Skin Absorption; Sumatriptan
PubMed: 27624669
DOI: 10.1016/j.xphs.2016.07.023 -
Clinical Drug Investigation Jan 2022A topical formulation of diclofenac (FLECTOR diclofenac epolamine topical system (FDETS)) is approved in adults for the treatment of acute pain due to minor strains,...
BACKGROUND AND OBJECTIVE
A topical formulation of diclofenac (FLECTOR diclofenac epolamine topical system (FDETS)) is approved in adults for the treatment of acute pain due to minor strains, sprains, and contusions; however, its safety and efficacy have not been investigated in a pediatric population. This study assessed the safety and efficacy of the FLECTOR (diclofenac epolamine) topical system in children.
METHODS
This was an open-label, single-arm, phase IV study at ten USA-based family medicine or pediatric practices in children aged 6-16 years with a clinically significant minor soft tissue injury sustained within the preceding 96 h and at least moderate spontaneous pain on the Wong-Baker FACES Pain Rating Scale. The FLECTOR topical system was applied twice daily until pain resolution or Day 14. The primary endpoint was local tolerability and systemic safety. Key secondary endpoints were diclofenac plasma concentrations and analgesic efficacy.
RESULTS
104 patients were enrolled; 52 were 6-11 years old, and 52 were 12-16 years old (mean age 11.6 years). The maximum tolerability score experienced by any patient was 1 (faint redness). Fourteen adverse events (none serious) in nine patients (8.7%) were considered possibly treatment-related. Reduction in pain during the study was somewhat greater for patients aged 6-11 versus 12-16 years (p < 0.011). The diclofenac plasma concentration tended to be higher in the younger age group compared with older patients: 1.83 versus 1.46 ng/mL at the first assessment and 2.49 versus 1.11 ng/mL at the last assessment (p = 0.002).
CONCLUSION
The FLECTOR topical system safely and effectively provided pain relief for minor soft tissue injuries in the pediatric population, with minimal systemic nonsteroidal anti-inflammatory drug exposure and low potential risk of local or systemic adverse events.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov identifier NCT02132247.
Topics: Acute Pain; Administration, Topical; Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Child; Diclofenac; Humans; Pyrrolidines; Soft Tissue Injuries
PubMed: 34826122
DOI: 10.1007/s40261-021-01101-x