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The Science of the Total Environment Apr 2022Overuse and misapplication of veterinary pharmaceuticals affect the ecosystem, even at low concentrations. Vultures are mainly exposed to these compounds when feeding on... (Review)
Review
Overuse and misapplication of veterinary pharmaceuticals affect the ecosystem, even at low concentrations. Vultures are mainly exposed to these compounds when feeding on improperly disposed carcasses from animals treated before death. This produces diverse negative impacts on vulture health and populations, even leading to death. Using the available bibliography we determined which veterinary pharmaceuticals vultures are exposed to worldwide and assessed the potential consequences for these species. Based on the responsibilities of the different stakeholders, we also propose action to mitigate this problem. Of 104 articles addressing vulture exposure to veterinary pharmaceuticals, most came from Asia, Europe and Africa; almost no information was available on the Americas. Vultures were reported as being exposed to non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, anti-parasitic and euthanizing agents. Most available information is related to the catastrophic effect of the NSAID diclofenac in South Asia. Vultures are particularly exposed to veterinary drugs when ingesting carcasses from intensive livestock production, but other potential pathways (e.g., discards from salmon farms or fisheries) have not yet been properly evaluated. It is essential to improve scientific information on this topic - increasing the range of drugs and geographical areas studied - in order to implement sustainable conservation action for these birds. A combination of strategies could prove effective in reducing the impact of pharmaceuticals on the environment and non-target species. To mitigate this conservation problem, a set of multilateral actions should therefore be implemented, involving diverse stakeholders such as government representatives, pharmaceutical companies, veterinary practitioners, scientists and conservation agents, and local communities.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Ecosystem; Falconiformes; Veterinary Drugs
PubMed: 35016927
DOI: 10.1016/j.scitotenv.2021.152884 -
The American Journal of Psychiatry Sep 2019
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Methylphenidate
PubMed: 31474129
DOI: 10.1176/appi.ajp.2019.19070681 -
Journal of Chromatographic Science Dec 2023A reversed-phase high-performance liquid chromatography method was developed and validated for the simultaneous determination of pridinol, diclofenac and...
A reversed-phase high-performance liquid chromatography method was developed and validated for the simultaneous determination of pridinol, diclofenac and diclofenac-related compounds in tablet formulations. The proposed method is also suitable for content uniformity determination, for dissolution test and for stability studies. Separation was achieved on a base-deactivated silica C8 column, using 50 mM phosphate buffer (pH 2.5) and methanol (40:60 v/v) as mobile phase, at a flow rate of 1.0 mL/min and column temperature of 40°C. Ultraviolet detection was made at 225 nm. The method was validated for specificity, accuracy, precision (intraday and interday levels) and linearity for each analyte. For diclofenac impurity A, sensitivity was also studied. The method showed specificity and linearity (R2: 0.999 for the three analytes) over the assessed concentration range (diclofenac: 2.5-75.0 μg/mL, pridinol: 2.0-60.0 μg/mL and impurity A: 1.25-5.0 μg/mL) and demonstrated good precision as reflected by the low coefficient of variation in all cases. Recovery rates obtained were 99.81, 100.58 and 100.96% for diclofenac, pridinol and impurity A respectively, and for all three analytes, the variances of the concentrations tested were equivalent. The detection and quantitation limits for impurity A were 0.078 and 0.261 μg/mL, respectively.
Topics: Diclofenac; Chromatography, High Pressure Liquid; Piperidines; Tablets
PubMed: 36912069
DOI: 10.1093/chromsci/bmad017 -
CPT: Pharmacometrics & Systems... May 2021Establishing bioequivalence (BE) for dermatological drug products by conducting comparative clinical end point studies can be costly and the studies may not be... (Review)
Review
Establishing bioequivalence (BE) for dermatological drug products by conducting comparative clinical end point studies can be costly and the studies may not be sufficiently sensitive to detect certain formulation differences. Quantitative methods and modeling, such as physiologically-based pharmacokinetic (PBPK) modeling, can support alternative BE approaches with reduced or no human testing. To enable PBPK modeling for regulatory decision making, models should be sufficiently verified and validated (V&V) for the intended purpose. This report illustrates the US Food and Drug Administration (FDA) approval of a generic diclofenac sodium topical gel that was based on a totality of evidence, including qualitative and quantitative sameness and physical and structural similarity to the reference product, an in vivo BE study with PK end points, and, more importantly, for the purposes of this report, a virtual BE assessment leveraging dermal PBPK modeling and simulation instead of a comparative clinical end point study in patients. The modeling approach characterized the relationship between systemic (plasma) and local (skin and synovial fluid) diclofenac exposure and demonstrated BE between the generic and reference products at the presumed site of action. Based on the fit-for-purpose modeling principle, the V&V process involved assessing observed data of diclofenac concentrations in skin tissues and plasma, and the overall performance of the modeling platform for relevant products. Using this case as an example, this report provides current scientific considerations on good practices for model V&V and the establishment of BE for dermatological drug products when leveraging PBPK modeling and simulation for regulatory decision making.
Topics: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans; Models, Biological; Skin; Therapeutic Equivalency
PubMed: 33547863
DOI: 10.1002/psp4.12600 -
Neuropsychopharmacology : Official... Oct 2023Methylphenidate is a widely used and effective treatment for attention-deficit/hyperactivity disorder (ADHD), yet the underlying neural mechanisms and their relationship... (Randomized Controlled Trial)
Randomized Controlled Trial
Methylphenidate is a widely used and effective treatment for attention-deficit/hyperactivity disorder (ADHD), yet the underlying neural mechanisms and their relationship to changes in behavior are not fully understood. Specifically, it remains unclear how methylphenidate affects brain and behavioral dynamics, and the interplay between these dynamics, in individuals with ADHD. To address this gap, we used a novel Bayesian dynamical system model to investigate the effects of methylphenidate on latent brain states in 27 children with ADHD and 49 typically developing children using a double-blind, placebo-controlled crossover design. Methylphenidate remediated greater behavioral variability on a continuous performance task in children with ADHD. Children with ADHD exhibited aberrant latent brain state dynamics compared to typically developing children, with a single latent state showing particularly abnormal dynamics, which was remediated by methylphenidate. Additionally, children with ADHD showed brain state-dependent hyper-connectivity in the default mode network, which was also remediated by methylphenidate. Finally, we found that methylphenidate-induced changes in latent brain state dynamics, as well as brain state-related functional connectivity between salience and default mode networks, were correlated with improvements in behavioral variability. Taken together, our findings reveal a novel latent brain state dynamical process and circuit mechanism underlying the therapeutic effects of methylphenidate in childhood ADHD. We suggest that Bayesian dynamical system models may be particularly useful for capturing complex nonlinear changes in neural activity and behavioral variability associated with ADHD. Our approach may be of value to clinicians and researchers investigating the neural mechanisms underlying pharmacological treatment of psychiatric disorders.
Topics: Humans; Child; Methylphenidate; Attention Deficit Disorder with Hyperactivity; Bayes Theorem; Brain; Nerve Net; Central Nervous System Stimulants
PubMed: 37491674
DOI: 10.1038/s41386-023-01668-3 -
Environmental Technology Nov 2021In this study, peracetic acid (PAA) activated by Fe(II) was proposed to remove diclofenac (DCF) in polluted water. It was found that Fe(II)/PAA system could effectively...
In this study, peracetic acid (PAA) activated by Fe(II) was proposed to remove diclofenac (DCF) in polluted water. It was found that Fe(II)/PAA system could effectively remove DCF at neutral condition, which has a significant advantage over classical Fenton process. According to the result of scavenging experiment, both hydroxyl radical and peroxy radical were considered to be responsible for the degradation of DCF. The influence of several operational parameters including initial pH, Fe(II) dosage, PAA concentration and common water matrix on DCF removal were investigated. 80% DCF was removed at mild condition (pH 6-7) within 60 s, and its removal rate could be enhanced with the increase in Fe(II) dosage and PAA concentration. Presence of and natural organic matter (NOM) was proved to have a significantly negative impact on DCF degradation. Four probable degradation pathways of DCF were proposed based on the detected reaction products, including hydroxylation, C-N bond cleavage, decarboxylation and dehydrogenation.
Topics: Diclofenac; Ferrous Compounds; Oxidation-Reduction; Peracetic Acid; Water Pollutants, Chemical
PubMed: 32295490
DOI: 10.1080/09593330.2020.1756926 -
Journal of Separation Science Jun 2023White analytical chemistry is a novel concept for the assessment of analytical methods on basis of its validation efficiency, greenness power, and economical efficiency....
White analytical chemistry-driven stability-indicating concomitant chromatographic estimation of thiocolchicoside and aceclofenac using response surface analysis and red, green, and blue model.
White analytical chemistry is a novel concept for the assessment of analytical methods on basis of its validation efficiency, greenness power, and economical efficiency. White analytical chemistry-driven stability indicating chromatographic method has been developed for the concomitant analysis of thiocolchicoside and aceclofenac. The proposed chromatographic method has been developed using a safe and environmental-friendly organic solvents for the concomitant stability study of thiocolchicoside and aceclofenac. The analytical risk assessment was carried out for the identification of high-risk analytical risk factors and analytical method performance attributes. The mixture design was applied for the design of experiments-based response surface modeling of high-risk analytical risk factors and analytical method performance attributes. The degradation products were isolated and characterized using infrared, nuclear magnetic resonance, and mass spectral data. The proposed method was compared for its validation efficiency, greenness power, and cost-efficiency with published chromatographic methods using the red, green, and blue models. The white score of the proposed and reported method was calculated by averaging the red, green, and blue scores of the methods. The proposed method was found to be robust, green, and economical for the concomitant stability study of thiocolchicoside and aceclofenac.
Topics: Chromatography, High Pressure Liquid; Diclofenac; Colchicine
PubMed: 36946645
DOI: 10.1002/jssc.202300139 -
Bioorganic & Medicinal Chemistry Letters Feb 2022In this paper, we designed and synthesized a series of novel phenylpiperazine-phenylacetate derivatives as rapid recovery hypnotic agents. The best compound 10 had...
In this paper, we designed and synthesized a series of novel phenylpiperazine-phenylacetate derivatives as rapid recovery hypnotic agents. The best compound 10 had relatively high affinity for the GABA receptor and low affinity for thirteen other off-target receptors. In three animal models (mice, rats, and rabbits), compound 10 exerted potent hypnotic effects (HD = 5.2 mg/kg in rabbits), comparable duration of the loss of righting reflex (LORR), and significant shorter recovery time (time to walk) than propanidid. Furthermore, compound 10 (TI = 18.1) showed higher safety profile than propanidid (TI = 14.7) in rabbits. Above results suggested that compound 10 may have predictable and rapid recovery profile in anesthesia.
Topics: Animals; Drug Design; Guinea Pigs; Hypnotics and Sedatives; Male; Mice; Phenylacetates; Piperazines; Rabbits; Rats, Sprague-Dawley; Receptors, GABA-A; Rats
PubMed: 34896213
DOI: 10.1016/j.bmcl.2021.128497 -
Journal of Drug Targeting Sep 2022Effective and safe therapies to counteract persistent inflammation are necessary. We developed erythrocyte-derived liposomes (EDLs) with intrinsic anti-inflammatory...
Effective and safe therapies to counteract persistent inflammation are necessary. We developed erythrocyte-derived liposomes (EDLs) with intrinsic anti-inflammatory activity. The EDLs were prepared using lipids extracted from erythrocyte membranes, which are rich in omega-3 fatty acids with several health benefits. Diclofenac, a widely used anti-inflammatory drug, was incorporated into EDLs in relevant therapeutic concentrations. The EDLs were also functionalised with folic acid to allow their active targeting of M1 macrophages, which are key players in inflammatory processes. In the presence of lipopolysaccharide (LPS)-stimulated macrophages, empty EDLs and EDLs incorporating diclofenac were able to reduce the levels of important pro-inflammatory cytokines, namely interleukin-6 (IL-6; ≈85% and 77%, respectively) and tumour necrosis factor-alpha (TNF-α; ≈64% and 72%, respectively). Strikingly, cytocompatible concentrations of EDLs presented similar effects to dexamethasone, a potent anti-inflammatory drug, in reducing IL-6 and TNF-α concentrations, demonstrating the EDLs potential to be used as bioactive carriers in the treatment of inflammatory diseases.
Topics: Anti-Inflammatory Agents; Cytokines; Diclofenac; Erythrocytes; Humans; Inflammation; Interleukin-6; Liposomes; Tumor Necrosis Factor-alpha
PubMed: 35414285
DOI: 10.1080/1061186X.2022.2066107 -
Small (Weinheim An Der Bergstrasse,... Jun 2024Osteoarthritis (OA) is a typical joint degenerative disease that is prevalent worldwide and significantly affects the normal activities of patients. Traditional...
Osteoarthritis (OA) is a typical joint degenerative disease that is prevalent worldwide and significantly affects the normal activities of patients. Traditional treatments using diclofenac (DCF) as an anti-inflammatory drug by oral administration and transdermal delivery have many inherent deficiencies. In this study, a lubricating microneedles (MNs) system for the treatment of osteoarthritis with multistage sustained drug delivery and great reduction in skin damage during MNs penetration is developed. The bilayer dissolvable MNs system, namely HA-DCF@PDMPC, is prepared by designating the composite material of hyaluronic acid (HA) and covalently conjugated drug compound (HA-DCF) as the MNs tips and then modifying the surface of MNs tips with a self-adhesive lubricating copolymer (PDMPC). The MNs system is designed to achieve sustained drug release of DCF via ester bond hydrolysis, physical diffusion from MNs tips, and breakthrough of lubrication coating. Additionally, skin damage is reduced due to the presence of the lubrication coating on the superficial surface. Therefore, the lubricating MNs with multistage sustained drug delivery show good compliance as a transdermal patch for OA treatment, which is validated from anti-inflammatory cell tests and therapeutic animal experiments, down-regulating the expression levels of pro-inflammatory factors and alleviating articular cartilage destruction.
Topics: Osteoarthritis; Animals; Drug Delivery Systems; Needles; Diclofenac; Hyaluronic Acid; Lubrication; Humans; Delayed-Action Preparations
PubMed: 38225701
DOI: 10.1002/smll.202307281