Concentrations Of Fluoxetine Research Articles

Submicromolar electrochemical sensing platform for fast Fluoxetine quantification based on Nb2CTx MXene and nitrogen-doped graphene oxide nanocomposites

A facile and novel electrochemical determination of Fluoxetine (FLX) at submicromolar concentration Niobium carbide (Nb2CTx) and Nitrogen-doped Reduced Graphene Oxide (NRGO) hybridized electrodes as sensing platform is demonstrated. Herein, Niobium carbide (Nb2CTx) was successfully prepared by etching Nb2AlC and then ultrasonically compounded with Nitrogen-doped Reduced Graphene Oxide (NRGO), to form a well-dispersed Nb2CTx/NRGO composite, which was modified onto a glassy carbon electrode (GCE). The morphology, structure and electrochemical property of the Nb2CTx/NRGO/GCE was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The electrocatalytic activity of the Nb2CTx/NRGO/GCE for FLX oxidation was studied in detail. The peak currents showed two good linear relationships (R2 = 0.9962 and 0.9949) with FLX concentrations (1.0–10 µM and 10–100 µM) and a detection limit of 0.34 µM (S/N = 3). The sensor has good selectivity, repeatability, reproducibility and stability, and is capable of sensitively determining FLX in human serum and urine samples of clinical biological fluids. This work is believed to be of great significance and of broad interest for research on innovative MXene materials development and biomedical sensing applications.

Therapeutic Drug Monitoring in Children and Adolescents: Findings on Fluoxetine from the TDM-VIGIL Trial.

Fluoxetine is the recommended first-line antidepressant in many therapeutic guidelines for children and adolescents. However, little is known about the relationships between drug dose and serum level as well as the therapeutic serum reference range in this age group. Within a large naturalistic observational prospective multicenter clinical trial ("TDM-VIGIL"), a transdiagnostic sample of children and adolescents (n = 138; mean age, 15; range, 7-18 years; 24.6% males) was treated with fluoxetine (10-40 mg/day). Analyses of both the last timepoint and all timepoints (n = 292 observations), utilizing (multiple) linear regressions, linear mixed-effect models, and cumulative link (mixed) models, were used to test the associations between dose, serum concentration, outcome, and potential predictors. The receiver operating curve and first to third interquartile methods, respectively, were used to examine concentration cutoff and reference values for responders. A strong positive relationship was found between dose and serum concentration of fluoxetine and its metabolite. Higher body weight was associated with lower serum concentrations, and female sex was associated with lower therapeutic response. The preliminary reference ranges for the active moiety (fluoxetine+norfluoxetine) were 208-328 ng/mL (transdiagnostically) and 201.5-306 ng/mL (depression). Most patients showed marked (45.6%) or minimal (43.5%) improvements and reported no adverse effects (64.9%). This study demonstrated a clear linear dose-serum level relationship for fluoxetine in youth, with the identified reference range being within that established for adults.

Acute Effects of Fluoxetine on Stress Responses and Feeding Motivation in Nile Tilapia

The selective serotonin reuptake inhibitor fluoxetine is one of the most commonly administered psychotropic medications; however, it has been recognized as toxic to aquatic life. In this study, we showed that stress responses and feeding motivation in Nile tilapia were affected by acute exposure to fluoxetine. To reach that conclusion, we exposed Nile tilapia to 0, 1 or 10 µg/L (environmentally/biologically relevant doses) of fluoxetine over a 24 h period and then exposed them to a handling stressor. We found that the 10 µg/L dose enhanced cortisol response to stress but caused an earlier decrease in the ventilation boost induced by that stressor. An immediate ventilation boost after stressful stimuli indicates sympathetic activation. Thus, this suggests that fluoxetine decreased sympathetic nervous system activity but augmented hypothalamus–pituitary–interrenal axis activity in the fish. Both feeding latency and ingestion were similar among the tested conditions; however, a multiple logistic regression model revealed that in the presence of a stressor or fluoxetine, the Nile tilapia tended to ingest less food but there was a higher probability of this decrease to be associated with fluoxetine. We concluded that acute exposure to environmentally/biologically relevant fluoxetine concentrations over 24 h acted as a modifying factor for Nile tilapia stress physiology and tended to interfere with feeding motivation. An acute stress response is an emergency reaction that contributes to the recovery of homeostasis. In the presence of fluoxetine, modifications of acute stress responses and the tendency to reduce food intake, which restricts the ability to replace the energy spent on stress responses, could compromise the resumption of homeostasis and an animal’s adjustment to different environmental contexts, such as those associated with aquaculture, in which anthropogenic stressors inevitably occur.

Cost-effective pharmaceutical implants in fish: validating the performance of slow-release implants for the antidepressant fluoxetine.

Internal, slow-release implants can be an effective way to manipulate animal physiology or deliver a chemical exposure over long periods of time without the need for an exogenous exposure route. Slow-release implants involve dissolving a compound in a lipid-based carrier, which is inserted into the body of an organism. However, the release kinetics of the compound from the implant to body tissues also requires careful validation. Here, we tested and validated a slow-release implant methodology for exposing fish to a pharmaceutical pollutant, fluoxetine. We tested two lipid-based carriers (coconut oil or vegetable shortening) in the common roach (Rutilus rutilus). The implants contained either a high (50 μg/g), low (25 μg/g), or control (0 μg/g) concentration of fluoxetine, and we measured tissue uptake in the brain, muscle, and plasma of implanted fish over 25 days. The two carriers released fluoxetine differently over time: coconut oil released fluoxetine in an accelerating manner (tissue uptake displayed positive quadratic curvature), while vegetable shortening released fluoxetine in a decelerating manner (negative quadradic curvature). For both carrier types, fluoxetine was measured at the highest concentration in the brain, followed by muscle and plasma. We showed that the implants delivered an internal exposure that would be similar to if fish were exposed in surface waters containing effluents by comparing the implant exposures to waterborne exposures in the published literature. Overall, we show that slow-release internal implants are an effective method for delivering chronic exposures of fluoxetine over at least one-month timescales. Internal exposures can be an especially powerful experimental tool when coupled with field-based study designs to assess the impacts of pharmaceutical pollutants in complex, natural environments. This article is protected by copyright. All rights reserved. Environ Toxicol Chem 2023;00:0-0. © 2023 SETAC.

Strategy to Minimize Plant Accumulation of Contaminants of Emerging Concern: Alternation between Treated Wastewater and Freshwater Irrigation

Treated wastewater (TWW) is increasingly used for agricultural irrigation in arid and semiarid areas, but it can introduce contaminants of emerging concern (CECs) into the food chain, posing a potential risk to human health. While many studies have shown that plants can accumulate some CECs, so far little effort has been made to explore mitigation strategies. This study tested the concept of alternating between TWW with conventional freshwater for irrigation to minimize CEC accumulation in plants. Tomato and lettuce seedlings were first cultivated in CEC-containing hydroponic solutions for 3 weeks, and then in CEC-free media for another 3 weeks. The plant tissues contained elevated concentrations of perfluorobutanesulfonate, perfluorobutanoic acid, perfluorohexanoic acid, carbamazepine, and fluoxetine ranging from 42.1 to 2724.2 ng/g (dry weight). However, after being transferred to CEC-free media, most CEC levels decreased by over 75%, attributed to plant metabolism, growth dilution and back release to culture media. This proof-of-concept study suggested that using TWW during the early part of the growing season may effectively minimize CEC accumulation. Such hybrid irrigation schemes have a great prospect for expanding the safe reuse of TWW and other lower-quality water sources in agriculture and should be further evaluated under field conditions.

Removal of fluoxetine from water by nanofiltration and reverse osmosis

This paper explores the use of nanofiltration (NF) and Reverse Osmosis (RO) to remove the pharmaceutical Fluoxetine (FLX) from water. This substance can be found in rivers and lakes and requires studies involving the application of efficient technologies for its removal or mitigation. The study evaluated NF and RO membranes as an alternative to remove Fluoxetine from water. NF removed fluoxetine within the range between 50 and 60%, and RO demonstrated higher efficiency in removing the drug (98.8%). RO is a suitable method as a complementary treatment of water to ensure a lower concentration of FLX in water.
 Keywords: emerging pollutants, environment, membrane technology, water treatment.

Long-term exposure to a pharmaceutical pollutant affects geotaxic behaviour in the adult but not juvenile life stage of killifish

Ecosystems around the world are increasingly polluted with pharmaceutical compounds that may perturb wildlife behaviour. Because many pharmaceuticals are continuously present in the aquatic environment, animals are often exposed to them across several life stages or even their entire life. Despite a large body of literature showing various impacts of exposure to pharmaceuticals on fish, hardly any long-term studies across different life stages have been conducted which makes it hard to accurately estimate the ecological outcomes of pharmaceutical pollution. Here, we performed a laboratory experiment in which we exposed hatchlings of the fish model Nothobranchius furzeri to an environmentally relevant concentration (0.5 μg/L) of the antidepressant fluoxetine until well into adulthood. We monitored total body length and geotaxic behaviour (i.e. gravity-mediated activity) of each fish as two traits that are ecologically relevant and naturally differ between juvenile and adult killifish. Fish exposed to fluoxetine were smaller compared to control fish, an effect that became more apparent as fish aged. Even though fluoxetine did not affect average swimming depth of either juveniles or adults, nor the time spent at the surface or bottom of the water column, exposed fish changed their position in the water column (depth) more frequently in the adult but not juvenile phase. These results suggest that important morphological and behavioural responses to pharmaceutical exposure–and their potential ecological consequences–may only emerge later in time and/or during specific life stages. Therefore, our results highlight the importance of considering ecologically relevant timescales across developmental stages when studying the ecotoxicology of pharmaceuticals.

Designing of ZnO nanoparticles oriented interface imprinted electrochemical sensor for fluoxetine detection

This study represents nanoparticle-based well-oriented recognition sites via interface imprinting, followed by selective and sensitive determination of fluoxetine (FLX). Herein, FLX was firstly immobilized onto ZnO NPs, and then polymerization was carried out with MAPA, HEMA, and EGDMA on the glassy carbon electrode via photopolymerization. After the etching of ZnO with and 10 mM HCI solution, a porous structure with recognition sites for FLX was constructed onto surface. The characterization of the electrochemical sensor was accomplished by utilizing CV, EIS, ATR-FTIR AFM, and SEM analysis. The DPV was used to determine FLX in standard solution, serum sample, and tap water. The effect of FLX concentration variation was studied using the DPV in the range of 1.0 × 10−11 M to 1.0 × 10−10 M with a detection limit of 2.67 × 10−12 M. This sensor showed specific recognition toward template, and more than 90% of its original response was retained after being stored in the desiccator at R.T. for 5 days. This technique has proven to be a powerful, highly selective, and sensitive tool for the rapid detection of FLX in tap water and spike serum samples.

Fluoxetine induces oxidative stress-dependent DNA damage in human hepatoma cells

<abstract> <p>Fluoxetine is a selective serotonin reuptake inhibitor that is a commonly used drug for the treatment of depression and obsessive-compulsive disorders. Despite the positive effects of this drug, it seems to be associated with various side effects. Genotoxicity or DNA damage is an important side effect of some kinds of drugs. To date, the genotoxicity and cytotoxicity of fluoxetine are partially unknown. In the present study, some oxidative stress methods were used, such as ROS, MDA and GSH evaluation methods in HepG2 cells treated with fluoxetine (1–10 µM). A comet assay was used to evaluate the genotoxic effects of fluoxetine, and flow cytometry was used for apoptosis detection in these hepatic cells. Our data have shown that fluoxetine increased MDA and intracellular concentration of ROS significantly (P < 0.001), while the amount of GSH was reduced significantly (P < 0.001). Our results also indicated that fluoxetine increased the DNA damage of HepG2 cells. The tail percentage of DNA for control cells was 4%, but this percentage was 19%, 28% and 32% for 1, 5 and 10 µM of fluoxetine concentration, respectively (P < 0.01 and P < 0.001). The flow cytometry results have also shown increases in early and late apoptosis for fluoxetine (13.31% and 9.54%, respectively). In conclusion, the present study has shown that fluoxetine is able to induce oxidative stress-dependent DNA damage. Anyway, more studies are needed to accurately explore the molecular and cellular aspects of fluoxetine.</p> </abstract>

Impact of Fluoxetine on Herbivorous Zooplankton and Planktivorous Fish.

The contamination of freshwater environments by pharmaceuticals is a growing problem. Modern healthcare uses nearly 3000 substances, many of which are designed to work at low dosages and act on physiological systems that have been evolutionarily conserved across taxa. Because drugs affect the organisms from different trophic levels, pharmaceutical pollution is likely to disturb species interactions. However, such effects are still only poorly understood. We investigated the impacts of environmentally relevant concentrations of the common drug fluoxetine (Prozac), an increasingly common contaminant of European waters, on predation behavior of crucian carp (Carassius carassius), a common planktivorous European fish, and the somatic growth of its prey, the water flea (Daphnia magna), a widespread planktonic crustacean. We exposed these two organisms to environmentally relevant levels of fluoxetine (360 ng L-1 ): the fish for 4 weeks and the water fleas for two generations. We tested the growth of the daphnids and the hunting behavior (reaction distance at which fish attacked Daphnia and feeding rate) of the fish under drug contamination. We found that Daphnia exposed to fluoxetine grew larger than a nonexposed cohort. The hunting behavior of C. carassius was altered when they were exposed to the drug; the reaction distance was shorter, and the feeding rate was slower. These effects occurred regardless of Daphnia size and the treatment regime they were subjected to. Our results suggest that contamination of freshwater environments with fluoxetine can disrupt the top-down ecological control of herbivores by reducing the hunting efficiency of fish and, as a consequence, may lead to increases in cladoceran population numbers. Environ Toxicol Chem 2023;42:385-392. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Ecotoxicological assessment of the effects of fluoxetine on Daphnia magna based on acute toxicity, multigenerational reproduction effects, and attraction-repellence responses

Fluoxetine, a common pharmaceutical used as an antidepressant, is already considered potentially hazardous to biota due to its increasing use and detection in European, North American, and Asian rivers. We studied the effects of fluoxetine on Daphnia magna, as we hypothesized that fluoxetine might have harmful effects, short and long-term, at different levels: survival, behaviour, and reproduction (offspring production). We applied two different approaches: (i) a scenario at environmentally relevant concentrations (0.1–1.0 μg/L) and (ii) a scenario simulating a future worsening of contamination (1–800 μg/L) until the reach of lethal concentrations. In the former, we examined whether there are multigenerational effects on reproduction and on the avoidance/colonisation behaviour in previously exposed populations. In the latter, three responses were assessed: survival, avoidance behaviour and reproduction. We did not detect differences in the reproduction output of D. magna among the treatments over the three generations examined. Irrespective of the multigenerational treatment, D. magna colonised the environments with fluoxetine in a similar way. In the second scenario, we determined the lethal concentration for 50% of the population (96 h-LC50 = 365 μg/L), which, in spite of the toxic effect, was attractive to organisms during the avoidance tests (24 h); in fact, D. magna were attracted (no repellence) even to the highest concentrations of fluoxetine tested (800 μg/L). Lastly, in a 21-day chronic toxicity test the reproduction output of D. magna increased with higher concentrations of fluoxetine. This effect might be related to the fact that the organisms in the contaminated treatment began their first reproduction earlier, when compared to that in the control treatments. In conclusion, this study discusses an identified hazard for aquatic biota due to the fluoxetine attraction effect and a predictive assessment of the consequences expected if its indiscriminate use increases.

Fluoxetine induces photochemistry-derived oxidative stress on Ulva lactuca

Emerging pollutants impose a high degree of stress on marine ecosystems, compromising valuable resources, the planet and human health. Pharmaceutical residues often reach marine ecosystems, and their input is directly related to human activities. Fluoxetine is an antidepressant, and one of the most prescribed selective serotonin reuptake inhibitors globally and has been detected in aquatic ecosystems in concentrations up to 40 μg L−1. The present study aims to evaluate the impact of fluoxetine ecotoxicity on the photochemistry, energy metabolism and enzyme activity of Ulva lactuca exposed to environmentally relevant concentrations (0.3, 0.6, 20, 40, and 80 μg L−1). Exogenous fluoxetine exposure induced negative impacts on U. lactuca photochemistry, namely on photosystem II antennae grouping and energy fluxes. These impacts included increased oxidative stress and elevated enzymatic activity of ascorbate peroxidase and glutathione reductase. Lipid content increased and the altered levels of key fatty acids such as hexadecadienoic (C16:2) and linoleic (C18:2) acids revealed strong correlations with fluoxetine concentrations tested. Multivariate analyses reinforced the oxidative stress and chlorophyll a fluorescence-derived traits as efficient biomarkers for future toxicology studies.

Investigation of effects of fluoxetine on the bronchial smooth muscles by the isolated organ bath system.

Airway smooth muscles (ASMs) play an essential role during breathing by contracting and relaxing as needed. Its dysfunction is related to some diseases such as asthma. The contractile mechanism of ASMs is complex. Therefore, research is necessary for this domain to identify issues and chemicals that can affect their contractions and impose health threats. This study aimed to investigate the effects of fluoxetine on the smooth muscles of the ASM using an isolated organ bath system. Fifteen male Sprague Dawley rats were divided into three groups: acetylcholine (ACh) group, fluoxetine group, and ACh + fluoxetine group. Following decapitation, 1-cm-long smooth muscle strips were prepared and placed in the isolated organ bath system Krebs' solution at 37°C (pH = 7.4), constantly bubbled with oxygen/carbon dioxide mixture (95%:5%), and isometric contractions were recorded. Contraction of the smooth muscle was achieved by 10-µM Ach, and contractile/relaxation effects of cumulative concentrations of fluoxetine (10-9-10-1M) were investigated. There was a numerical decrease in the contraction compared to ACh with no statistical significance in the ACh-fluoxetine group. There was a significant difference between the fluoxetine and the ACh groups (p < 0.05). In conclusion, fluoxetine had no contractile effect on ASM in isolated organ bath systems. Future studies are needed to evaluate the effects of oral usage of fluoxetine on the bronchial muscle in different experimental models to explain the adverse/beneficial effects of fluoxetine in the subjects, especially with respiratory conditions.

Antiviral treatment with fluoxetine for rituximab-associated chronic echovirus 13 meningoencephalitis and myofasciitis.

Enterovirus infections pose a serious threat for patients with humoral deficiencies and may be lethal, whilst the efficacy of proposed treatment options such as corticosteroids, intravenous immunoglobulins and fluoxetine remains debated. Viral clearance was investigated in a patient with rituximab-induced B-cell depletion and chronic echovirus 13 (E13) meningoencephalitis/myofasciitis in response to intravenous immunoglobulins and fluoxetine using sequential semi-quantitative E13 viral load measurements by real-time reverse transcription polymerase chain reaction. Fluoxetine concentrations in plasma and cerebrospinal fluid were determined by liquid chromatography mass spectrometry. Intravenous immunoglobulins appeared ineffective in this case of E13 infection, whereas virus clearance in cerebrospinal fluid was obtained after 167 days of oral fluoxetine. Since treatment with corticosteroids resulted in a flare of symptoms, rechallenge with viral load measurements was not attempted. In this report of a patient with rituximab-associated chronic echovirus 13 meningoencephalitis, viral clearance in response to single treatment options is assessed for the first time. Our observations further support the in vivo efficacy of fluoxetine against enteroviral infections. More research is needed to establish its efficacy in different enterovirus strains.

Investigation of the Removal of Several Micropollutants Presenting Different Ozone Reactivities from Natural Potable Water Matrix by the Application of Ozonation with the Use of SiO2 and Al2O3 as Catalysts

The aim of this study was to investigate the correlation between solid materials and micropollutants, aiming to enhance the removal of the latter during the application of the ozonation process. For that purpose, two solid materials (SiO2 and Al2O3) presenting catalytic activity were used for the removal of eight micropollutants from natural potable water, containing them either separately or in a mixture, by ozonation. The studied micropollutants, presenting different physicochemical properties, are atrazine, ibuprofen, p-CBA (ozone-resistant compounds), benzotriazole, caffeine (with moderate ozone reactivity), carbamazepine, fluoxetine, paracetamol (easily oxidized by ozone). The residual concentrations of carbamazepine, paracetamol, and fluoxetine were found to be lower than 5.9 μg/L, 1.2 μg/L, and 15.5 μg/L, respectively, after 1 min of oxidation time in all studied systems. In contrast, benzotriazole and caffeine removal was enhanced by the addition of catalysts; in both cases the best catalyst was SiO2. Regarding the ozone-resistant compounds, both examined materials enhanced the removal of ibuprofen and p-CBA; however, the best was found to be SiO2 and Al2O3, respectively. In contrast, Al2O3 cannot be considered as an effective catalyst for the removal of atrazine, which presents chemical affinity only with SiO2 and for this reason it can be removed to a higher extent by its presence. Similar results were observed in the study of the mixture, although in this system, the residual concentration of all micropollutants was found to be under the detection limit after the application of catalytic ozonation.

The selective serotonin reuptake inhibitor fluoxetine has direct effects on beta cells, promoting insulin secretion and increasing beta-cell mass.

AimThis study investigated whether therapeutically relevant concentrations of fluoxetine, which have been shown to reduce plasma glucose and glycated haemoglobin independent of changes in food intake and body weight, regulate beta‐cell function and improve glucose homeostasis.MethodsCell viability, insulin secretion, beta‐cell proliferation and apoptosis were assessed after exposure of MIN6 beta cells or isolated mouse and human islets to 0.1, 1 or 10 μmol/L fluoxetine. The effect of fluoxetine (10 mg/kg body weight) administration on glucose homeostasis and islet function was also examined in ob/ob mice.ResultsExposure of MIN6 cells and mouse islets to 0.1 and 1 μmol/L fluoxetine for 72 hours did not compromise cell viability but 10 μmol/L fluoxetine significantly increased Trypan blue uptake. The dose of 1 μmol/L fluoxetine significantly increased beta‐cell proliferation and protected islet cells from cytokine‐induced apoptosis. In addition, 1 μmol/L fluoxetine induced rapid and reversible potentiation of glucose‐stimulated insulin secretion from islets isolated from mice, and from lean and obese human donors. Finally, intraperitoneal administration of fluoxetine to ob/ob mice over 14 days improved glucose tolerance and resulted in significant increases in beta‐cell proliferation and enhanced insulin secretory capacity.ConclusionsThese data are consistent with a role for fluoxetine in regulating glucose homeostasis through direct effects on beta cells. Fluoxetine thus demonstrates promise as a preferential antidepressant for patients with concomitant occurrence of depression and diabetes.

Highly Sensitive Detection of the Antidepressant Fluoxetine With an Extended Gate Field Effect Transistor

Fluoxetine (FL) is one of the selective serotonin reuptake inhibitors, which is used as an anti-depressant, as well as anti-panic drug. In this work, a sensor for label-free recognition of trace amounts of FL is introduced, which is based on an extended gate field-effect transistor (EGFET). This sensor enables the detection and accurate measurement of FL concentrations over wide dynamic range. The sensing part of the device is a Pt electrode covered by a sensitive polyvinyl chloride (PVC) membrane. The functionalized Pt electrode acting as an extended gate of the EGFET, is connected to the internal gate of a MOSFET transducer. The sensing element of the PVC membrane is the insoluble ion-pair of FL cation and tetraphenylborate anion. The sensor performance for detection of FL was characterized in different ionic strengths of the matrix solution. Then, the sensor capability to operate in physiological phosphate-buffered saline (PBS) was assessed, where the sensor indicated two linear dynamic ranges of its response, with different sensitivities in 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−11</sup> -10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−5</sup> M and 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−5</sup> -10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−3</sup> M ranges. Also the calculated detection limit for the sensor was <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$2.63\times 10^{-12}$ </tex-math></inline-formula> M. Moreover, the selectivity of the sensor was examined and validated in the presence of Citalopram, which is another anti-depressant drug with a similar structure to FL. We proposed a comprehensive analytical mapping of current sensitivity in all working regimes of the EGFET, providing a guide to the design of optimized sensors in any integrated systems of interest. Finally, the sensor was successfully exploited to assay citalopram in its pharmaceutical formulation.

Organic Cation Transporters are Involved in Fluoxetine Transport Across the Blood-Brain Barrier In Vivo and In Vitro.

The research and development of drugs for the treatment of central nervous system diseases faces many challenges at present. One of the most important questions to be answered is, how does the drug cross the blood-brain barrier to get to the target site for pharmacological action. Fluoxetine is widely used in clinical antidepressant therapy. However, the mechanism by which fluoxetine passes through the BBB also remains unclear. Under physiological pH conditions, fluoxetine is an organic cation with a relatively small molecular weight (<500), which is in line with the substrate characteristics of organic cation transporters (OCTs). Therefore, this study aimed to investigate the interaction of fluoxetine with OCTs at the BBB and BBB-associated efflux transporters. This is of great significance for fluoxetine to better treat depression. Moreover, it can provide a theoretical basis for clinical drug combination. In vitro BBB model was developed using human brain microvascular endothelial cells (hCMEC/D3), and the cellular accumulation was tested in the presence or absence of transporter inhibitors. In addition, an in vivo trial was performed in rats to investigate the effect of OCTs on the distribution of fluoxetine in the brain tissue. Fluoxetine concentration was determined by a validated UPLC-MS/MS method. The results showed that amantadine (an OCT1/2 inhibitor) and prazosin (an OCT1/3 inhibitor) significantly decreased the cellular accumulation of fluoxetine (P <.001). Moreover, we found that N-methylnicotinamide (an OCT2 inhibitor) significantly inhibited the cellular uptake of 100 and 500 ng/mL fluoxetine (P <.01 and P <.05 respectively). In contrast, corticosterone (an OCT3 inhibitor) only significantly inhibited the cellular uptake of 1000 ng/mL fluoxetine (P <.05). The P-glycoprotein (P-gp) inhibitor, verapamil, and the multidrug resistance associated proteins (MRPs) inhibitor, MK571, significantly decreased the cellular uptake of fluoxetine. However, intracellular accumulation of fluoxetine was not significantly changed when fluoxetine was incubated with the breast cancer resistance protein (BCRP) inhibitor Ko143. Furthermore, in vivo experiments proved that corticosterone and prazosin significantly inhibited the brain-plasma ratio of fluoxetine at 5.5 h and 12 h, respectively. OCTs might play a significant role in the transport of fluoxetine across the BBB. In addition, P-gp, BCRP, and MRPs seemed not to mediate the efflux transport of fluoxetine.

All-Solid-State Potentiometric Platforms Modified with a Multi-Walled Carbon Nanotubes for Fluoxetine Determination.

Novel cost-effective screen-printed potentiometric platforms for simple, fast, and accurate assessment of Fluoxetine (FLX) were designed and characterized. The potentiometric platforms integrate both the FLX sensor and the reference Ag/AgCl electrode. The sensors were based on the use of 4′-nitrobenzo-15-crown-5 (ionophore I), dibenzo-18-crown-6 (ionophore II), and 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) (ionophore III) as neutral carriers within a plasticized PVC matrix. Multiwalled carbon nanotubes (MWCNTs) were used as a lipophilic ion-to-electron transducing material and sodium tetrakis [3,5-bis(trifluoromethyl)phenyl] borate (NaTFPB) was used as an anionic excluder. The presented platforms revealed near-Nernstian potentiometric response with slopes of 56.2 ± 0.8, 56.3 ± 1.7 and 64.4 ± 0.2 mV/decade and detection limits of 5.2 × 10−6, 4.7 × 10−6 and 2.0 × 10−7 M in 10 mM Tris buffer solution, pH 7 for sensors based on ionophore I, II, and III, respectively. All measurements were carried out in 10 mM tris buffer solution at pH 7.0. The interfacial capacitance before and after insertion of the MWCNTs layer was evaluated for the presented sensors using the reverse-current chronopotentiometry. The sensors were introduced for successful determination of FLX drug in different pharmaceutical dosage forms. The results were compared with those obtained by the standard HPLC method. Recovery values were calculated after spiking fixed concentrations of FLX in different serum samples. The presented platforms can be potentially manufacturable at large scales and provide a portable, rapid, disposable, and cost-effective analytical tool for measuring FLX.

Sustainable regeneration of a honeycomb carbon aerogel used as a high-capacity adsorbent for Fluoxetine removal

Pharmaceuticals and personal care products (PPCPs) harm ecosystems and human health. The focus is now being put on regulating discharges at wastewater treatment plants (WWTPs). Stressful and lonely lifestyles, accentuated by the COVID-19 outbreak, have led to an increase in the consumption of antidepressants, particularly in the form of Fluoxetine (FLX). A highly effective process for the removal of PPCPs is of key importance for the economic feasibility of the process in the industry. Consequently, a high-capacity adsorption/regeneration system is crucial to solving this problem. In this study, the removal of FLX by an adsorption process and the subsequent in situ regeneration of the adsorbent was evaluated in successive cycles. NQ40 honeycomb 3D carbon aerogel was employed as a high-capacity adsorbent, obtaining uptakes of 125.24 mg/g. A detailed study of NQ40 and the mechanisms governing the adsorption process was conducted, with chemisorption and intra-particle diffusion playing the main role. A Fenton and a Fenton-like process with peroxymonosulfate (PMS) were evaluated for regeneration purposes, finding hydrogen peroxide to be more efficient in removing a high concentration of FLX. A regeneration capacity of 98.85% was achieved in the first NQ40 adsorption-regeneration cycle and 98.04% in the second one, without negatively affecting the structural characteristics of NQ40. Therefore, with a high porosity, low density, high biocompatibility, high chemical stability and 3D structural stability, this aerogel is at the forefront of novel high-capacity adsorbent materials for industrial-scale use in WWTPs.