Carbamazepine Research Articles (Page 1)

Organic matter-driven hydroxyl radical generation enhances emerging pollutant removal in plant rhizosphere of constructed wetlands: Coupled direct and indirect effects.

Accelerating iron redox cycling via acetate modification: a ligand engineering for sustainable fenton-like oxidation.

The neutral macrocyclic iron(III) complex Fe(H2O)(LPYA) (3) is a homogeneous catalyst for the oxidation of organic micropollutants with hydrogen peroxide. The macrocyclic ligand incorporates two hybrid pyridinium amidate/amidate (hybrid PYA/A) N-donors and two sulfonamidate N-donors with an -N(CH3)- group bridging the two sulfonamidate functions. Anionic analogues of 3 in which the pyridinium group is replaced by o-phenylene (K[Fe(H2O)(Lo-P)] (1)) or by nitro-substituted o-phenylene (K[Fe(H2O)(Lo-P*)] (2)) were also synthesized. Complexes 1-3 were investigated as potential catalysts for the oxidative destruction by hydrogen peroxide of persistent micropollutants that remain in wastewater after conventional treatment regimens. Complexes 1-3 catalyzed the oxidation of the surrogate micropollutants Orange II and Safranine O, and kinetic parameters for these reactions were obtained. 3 also catalyzed the oxidation of carbamazepine (CBZ), which is an actual persistent micropollutant under conditions that are relevant for practical applications ([3] 50 nM, [CBZ] 50 μM, [H2O2] 250 μM, i.e., 8.5 ppm, 25 °C, pH 7.0). Complex 3 catalyzed the oxidation of each of the above substrates at rates three to four times greater than those of the benchmark homogeneous catalyst for reactions of this type.

Abstract Twelve pharmaceuticals, including stimulant caffeine (CAFF), anti-inflammatories (naproxen (NPX), ibuprofen (IBU), and diclofenac (DCF)), antibiotics (anhydro-erythromycin (AETM), azithromycin (ATM), erythromycin (ETM), clindamycin (CMC), ciprofloxacin (CFC), sulfamethoxazole (SMX), and trimethoprim (TMP)), and the antiepileptic carbamazepine (CBZ), were analyzed in surface waters and sediments in the Ishmi River basin, Albania, across seasons during 2023 and 2024. This basin is characterized by limited wastewater treatment infrastructure, varying degrees of urban impact, and different environmental conditions. All targeted compounds were detected in water, with the highest concentrations observed near urban areas, particularly at the wastewater-impacted location LR1 for CAFF, IBU, NPX, and CFC with 22.5, 12.8, 2.7, and 1.8 µg L −1 , respectively. Sediment concentrations showed high levels of CFC and ATM, notably during spring with the highest concentrations of 1068 (LR1) and 396 ng g −1 (IR2), respectively, suggesting strong seasonal and spatial variability. Partitioning behavior ( K d and K oc ) was investigated in relation to compound-specific ( D ow ) and sediment-specific (pH, organic carbon, CaCO 3 and metal content) properties. Significant correlations were found, and multiple regression models successfully predicted in situ K d values for NPX, IBU, CFC, AETM, and CMC. These findings underline the influence of environmental and sediment characteristics on environmental pharmaceutical distribution.

Crohn's disease (CD) is an inflammatory gastrointestinal disorder marked by impaired autophagy due to inefficient bacterial uptake. We studied the effects of autophagy modulation using Tat-beclin-1 and carbamazepine (CBZ) on dendritic cells (DCs) and Paneth cell functionality in pediatric CD patients. Twenty CD children genotyped for the ATG16L1 rs2241880 polymorphism and 10 healthy controls were enrolled. DCs were incubated with fluorochrome-conjugated particles of Escherichia coli or DQ-ovalbumin after pretreatment with CBZ or Tat-beclin-1 to evaluate antigen processing. Treated DCs were stained for P62, LAMP1, and LC3, and analyzed by confocal microscopy. Paneth cells from biopsies were pretreated with both drugs, stained for lysozyme, and analyzed by transmission electron microscopy. Antigen processing increased after Tat-beclin-1 and CBZ treatment in all groups. DCs expressed higher activation markers HLA-DR and CD86+, notably in high-risk patients, who also showed increased DQ-OVA processing. The number of lysozymes in Paneth cells from controls did not change after Tat-beclin-1 treatment, while in the CD group, it decreased significantly, suggesting increased exocytosis. CBZ treatment increased secretory granules only in CD inflamed tissue. Our results indicate that CBZ and Tat-beclin-1 enhance autophagic flux, representing a novel approach to treating pediatric CD patients.

This article reviews the evidence for drug-nutrient (DN) interactions associated with the chronic use of commonly prescribed psychiatric medications and suggests management strategies. Nutrient deficiencies due to DN interactions pose a risk for poorer patient outcomes. However, DN interaction studies and guidelines on preventing and managing DN abnormalities are lacking, with limited information for healthcare providers and patients to use as a resource. DN interactions can be caused by chronic use of psychiatric medications. Carbamazepine (CBZ), valproic acid (VPA), tricyclic antidepressants (TCAs), antipsychotics, and lithium can cause various vitamin B deficiencies. Calcium and/or vitamin D levels can be decreased by CBZ, VPA, antidepressants (ie, TCAs and selective serotonin reuptake inhibitors), and antipsychotics. VPA and clozapine can cause selenium deficiency. VPA may also lower carnitine and zinc levels, while VPA and CBZ can decrease vitamin E levels. Lastly, coenzyme Q10 levels can be reduced by TCA use. Strategies for the detection and treatment of these deficiencies are provided in the article. Although widespread supplementation is not recommended, identifying at-risk individuals taking psychiatric medications for evaluation and, if needed, treatment can improve their nutrient status. The summary evidence provided can assist pharmacists in guiding recommendations for patient care.

Despite the benefits of pharmaceuticals in medicine, concerns about their presence in wastewater sludge highlight the need for sustainable strategies that focus on reducing and managing their environmental release. Introducing pharmaceutical residues into the environment through the land application of biosolids poses substantial risks to the public and the ecosystem. As a way to reduce pharmaceutical contamination in biosolids, a study was conducted using biochemical methane potential (BMP) assays to evaluate the effectiveness of electromagnetic heating methods for advancedanaerobic digestion (AD). Thermal sludgepretreatment was evaluated using radio frequency (RF) heating at 13.56MHz and microwave (MW) heating at 2450MHz. Both methods are compared in terms of reducing ubiquitous pharmaceuticals, specifically ibuprofen (IBP), diclofenac (DCF), and carbamazepine (CBZ). Both pretreatments enhanced the removal of pharmaceuticals by facilitating their transformation into more accessible and biodegradable forms in both the aqueous and total phases of the sludge. In particular, RF heating yielded a DCF removal efficiency of 92% in the aqueous phase of sludge. Even IBP and DCF accumulated in control BMPs incubated under both thermophilic and mesophilic conditions, thermal pretreatment facilitated the co-metabolic degradation of target pharmaceuticals through an accelerated hydrolysis stage, resulting in their improved removal during advanced digestion. Compared to the control, RF pretreatment combined with AD improved DCF removal by 17% in the total phase and increased persistent CBZ removal by 5%. Thermal pretreatment also reduced the release of pharmaceuticals into the aqueous phase during advanced digestion compared to the control. Considering the feasibility of RF and MW heatings at full scale, the integration of energy-efficient RF heating technology into digestion is preferred to reduce pharmaceutical levels building up in the ultimate disposal route, including both the centrate side streams and agricultural land.

Balancing foetal disadvantage and seizure freedom in women capable of pregnancy - the Australian pregnancy register experience.

Effects of dibenzazepine compounds on Nav1.2 channels and neuronal network activity: A systematic comparison.

Combining electrocoagulation-flotation with anaerobic digestion for faecal sludge treatment: Micropollutant removal with simultaneous energy recovery.

Efficient degradation of carbamazepine by electro-Fenton coupled with persulfate activation by FeCo-PBA catalyst and its mechanism.

Linking contaminant levels in Tepetitlán reservoir to zebrafish (Danio rerio) embryotoxicity and gene expression responses.

This study provides insights into the in vivo performance of amorphous solid dispersion (ASD) formulations of a poorly water-soluble drug through deconvolution analysis using a surrogate marker for drug release. Carbamazepine (CAR) and fenofibrate (FEN) were used as surrogate markers of drug release from formulations and as a model of a poorly water-soluble drug, respectively. Three ASDs containing CAR (3 wt %) and FEN (30 wt %) were prepared using hydroxypropyl methylcellulose (HPMC) with immediate-release characteristics (ASD-HPMC) and two HPMC derivatives (HPMC acetate succinate, HPMCAS) exhibiting different pH-dependent drug release profiles (ASD-HPMCAS-LF and ASD-HPMCAS-HF). The in vitro drug release profiles of FEN for each ASD were comparable to those of CAR, with both compounds demonstrating polymer-dependent release behavior (release rate: ASD-HPMC > ASD-HPMCAS-LF > ASD-HPMCAS-HF). Slower FEN release prolonged the time to reach the maximum concentration; however, the maximum concentration itself was not affected. The improved oral FEN absorption in rats ranked as follows: ASD-HPMC > ASD-HPMCAS-HF > ASD-HPMCAS-LF, while CAR was completely absorbed regardless of the polymer used. Plasma CAR profile deconvolution analysis revealed that the in vivo drug release profiles corresponded to the in vitro release results. In the FEN absorption rate time-profiles, a hybrid parameter combining the drug concentration and absorption clearance, derived from deconvolution analysis, showed that ASD-HPMC maintained a relatively high and stable absorption rate until complete absorption. Conversely, ASD-HPMCAS-LF exhibited a half absorption rate compared to ASD-HPMC over 1.5 h, which then declined rapidly, resulting in limited FEN absorption improvement. For ASD-HPMCAS-HF, the absorption rate gradually increased and remained at half the rate compared to ASD-HPMC over 6 h, leading to an intermediate improvement in FEN absorption in three ASDs. These differences in absorption rate profiles indicate that drug release profiles significantly affect the amount of dissolved FEN, its retention time in the gastrointestinal tract, and the effective surface area available for absorption. This study demonstrates that the proposed method enables reliable evaluation of the in vivo performance of ASD formulations.

While oxidative reactive species (RS) have been extensively studied for their critical role in trace organic contaminant (TrOC) degradation, the mechanistic contributions of reductive RS in aquatic environments remain poorly understood. In this study, we report a previously unrecognized photochemical pathway for generating a highly reductive carbon dioxide radical anion (CO2• -) through synergistic interactions between excited triplet-state dissolved organic matter (3DOM*) and ubiquitous low-molecular-weight carboxylic acids (LCAs) in surface waters. Using carbamazepine (CBZ) as a model compound, electron paramagnetic resonance confirmed photogenerated CO2• - in mixed oxalic acid and anthraquinone-2-sulfonate (AQ2S) systems, driving a 429% increase in the CBZ photodegradation rate with respect to AQ2S alone. The CO2• --driven enhancement was generalizable across diverse 3DOM* surrogates and LCAs as well as natural DOM samples. By combining advanced ab initio molecular dynamics simulations, quantum chemical calculations, and mass spectrometry analysis, we demonstrate that photogenerated CO2• - initiates ultrafast (within picoseconds) electron transfer reactions with CBZ, leading to the formation of degradation products. This study not only reveals a new source of reductive CO2• - in surface waters but also suggests the important role of reductive RS in the TrOC transformation in sunlit surface waters.

Facile synthesis of high loading and highly electron-delocalized Co single-atom catalyst for PMS activation: An in-depth study of molecular orbital and catalytic mechanisms.

Background: Cancer metastasis is facilitated by voltage-gated sodium channels (VGSCs) through the extracellular matrix (ECM) degradation. VGSCs play a pivotal role in cancer invasion during its epithelial-mesenchymal transition; hence, decreasing treatability. Tetrodotoxin (TTX) is a potent, selective neurotoxin that blocks VGSCs, particularly Nav1.7, which is overexpressed in carcinomas, especially type II endometrial and ductal carcinomas. TTX is found mainly in puffer fish (Fugu) and other marine and terrestrial animals used in traditional Japanese cuisine. TTX carries the potential for therapeutic applications; however, it’s limited by a high toxicity and narrow therapeutic index (NTI), requiring precise dosage control for medicinal use [38]. Thus, TTX appropriate adjustment could give novel anti-metastatic agent, while maintaining a non-toxic concentration for human, what is very important. Limited insights exist on TTX's toxicology and therapeutic potential. Objective: This study employed a multifaceted approach to evaluate the therapeutic potential of TTX in inhibiting carcinoma metastasis while ensuring concentrations remain within non-toxic levels for humans. Due to the hazardous nature of TTX, Carbamazepine (CBZ), an anticonvulsant known to block Nav1.7, was selected as a reference compound. CBZ's established pharmacokinetic profile and lower toxicity allowed for safer experimental handling and provided a comparative baseline for TTX's efficacy. Since collecting volumetric data on CBZ, according to Mohr’s method, was unfeasible due to its fully molecular composition, Verapamil was introduced as a similar channel-blocking drug in chloride salt form. Methods: Verapamil chloride was used for precipitation titration to estimate CBZ’s effective (ED50), toxic (TD50), and lethal (LD50) doses. This was done by using the ED50 of Verapamil and transcribing it to CBZ, as they have very similar TI. Similar tactics were carried out for the determination of the ED50 of TTX in concentration form, yielding its therapeutic dose. TI of TTX was calculated. Molecular Docking analysis of both CBZ and TTX’s interaction with Nav1.7, independently 5 times using 20 starting conformations for each compound, with the virtual box size not exceeding 27,000 Å. Results: In silico analysis showed that TTX binds to Nav1.7 within a pocket, demonstrating lower affinity but greater efficacy due to site-specific interactions, while CBZ binds on a more exposed level with less efficacy. Volumetric dosage-adjustment analysis indicated that, while TTX has NTI ≈ 1.6, careful administration could allow localized carcinoma treatment at 1.737×10⁻⁸ mol cm⁻³/kg. The findings support the hypothesis that TTX, in controlled dosage-adjustment and targeted delivery, could inhibit carcinoma metastasis. Conclusion: TTX has the potential to inhibit the invasion of carcinoma cells, especially those of ductal and type II endometrial carcinomas, by selectively blocking Nav1.7. Careful dosage control and targeted drug delivery systems (which would vary with the stage of the cancer’s development) are necessary to minimize systemic toxicity. Further research is required to practically develop safe administration methods to enhance TTX’s therapeutic viability, with in vivo methodologies. Keywords: Cancer, tetrodotoxin (TTX), voltage-gated sodium channels (VGSCs), carbamazepine (CBZ), novel anti-metastatic agent, verapamil, bioactive, functional food.

ABSTRACTPopulation pharmacokinetic (PK) models are commonly used to predict drug concentrations, but artificial intelligence (AI) models have gained interest due to their ability to identify complex patterns without requiring mathematical assumptions. This study compares the predictive performance of AI and population PK models using therapeutic drug monitoring (TDM) records of four antiepileptic drugs (AEDs): carbamazepine (CBZ), phenobarbital (PHB), phenytoin (PHE), and valproic acid (VPA). Additionally, we analyzed key covariates influencing drug concentration predicting using the most accurate model. We extracted concentration data for CBZ, PHB, PHE, and VPA from TDM reports at Seoul National University Hospital (2010–2021), along with patient diagnoses and lab results. The predictive performances of 10 AI models, including ensemble and deep learning models, were compared with published population PK models. The predictive performance of AI models generally exceeded that of population PK models. The best‐performing AI models, such as Adaboost, eXtreme Gradient Boosting, and Random Forest, had lower root mean squared error values for CBZ, PHB, PHE, and VPA (2.71, 27.45, 4.15, and 13.68 μg/mL, respectively) compared to population PK models (3.09, 26.04, 16.12, and 25.02 μg/mL). The most influential covariate was time after last drug administration. AI models, particularly ensemble methods, showed strong predictive performance and may support individualized AED dosing, improving therapeutic outcomes while minimizing adverse effects.

ObjectiveThis study aimed to investigate the effects of different antiseizure medications (ASMs) and clinical treatment response on interictal electrocardiographic (ECG) repolarization indices and echocardiographic structural and functional cardiac parameters in patients with epilepsy.MethodsThis single-center, prospective, cross-sectional study was conducted between August 2024 and February 2025 at the Neurology and Cardiology Departments of Siirt Training and Research Hospital. The study included 97 patients with epilepsy and 57 age- and sex-matched healthy controls. Patients were classified as drug-sensitive or drug-resistant based on the International League Against Epilepsy (ILAE) criteria. While both monotherapy and polytherapy users were included in clinical comparisons, subgroup analyses by ASM type involved only monotherapy patients. ECG and echocardiographic parameters were assessed. Group comparisons and correlation analyses were performed using analysis of variance (ANOVA), chi-square test, and Pearson correlation.ResultsNo significant differences in demographic or interictal ECG repolarization indices were found between the drug-sensitive, drug-resistant, and control groups (P > 0.05). Both epilepsy groups had significantly higher left atrial volum index (LAVi) compared to controls (P < 0.001), while A velocity and lateral E′ were significantly lower. Carbamazepine (CBZ) group showed the highest LAVi, though without correlation to treatment duration. In contrast, valproic acid (VPA) and levetiracetam (LEV) groups exhibited significant positive correlations between treatment duration and LAVi (r = 0.776, P = 0.002; r = 0.571, P = 0.002, respectively).ConclusionTreatment with ASMs in epilepsy is associated with left atrial enlargement, particularly with CBZ. The absence of interictal ECG repolarization differences suggests that isolated assessments may be insufficient, supporting long-term cardiac monitoring in epilepsy management.

BackgroundSodium valproate (VPA) is widely recognized as the first-line treatment for patients with epilepsy (PWE). However, current studies lack evidence to determine the best add-on medication following VPA monotherapy failure. Lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), topiramate (TPM), and carbamazepine (CBZ) also exhibit broad-spectrum activity for seizures. This study aims to compare the therapeutic efficacy of different anti-seizure medication combinations in PWE following valproate monotherapy failure.MethodsIndividuals were categorized into five groups: VPA + LTG, VPA + LEV, VPA + TPM, VPA + OXC and VPA + CBZ. Each group was further subdivided based on seizure type: generalized onset, focal onset, or unknown onset. The effectiveness of these five groups was compared using variance, χ2 test and Kaplan–Meier survival analysis.ResultsA total of 2656 PWEs were included in this study. The ≥ 50% response rates for subjects with generalized epilepsy when combining VPA with LTG, OXC, LEV, TPM, and CBZ were 89.6%, 81.0%, 77.9%, 77.7%, and 75.9%, respectively. The LTG group demonstrated significantly higher efficacy than the LEV, TPM, and CBZ groups (P < 0.05). The ≥ 50% response rate of LTG, OXC, LEV, TPM and CBZ for subjects with focal epilepsy were 86.3%, 88.9%, 79.3%, 75.9% and 74.8%, respectively; with the OXC group being significantly more effective than the LEV, TPM, and CBZ groups (P < 0.05).ConclusionsIn this real-world study, we assessed the effectiveness of five anti-seizure medications as add-on therapy for PWE who failed sodium valproate monotherapy. Our findings suggest that combining LTG may be more effective for subjects with generalized epilepsy, while combining OXC may be more effective for subjects with focal epilepsy.

The inefficient degradation of emerging organic contaminants (EOCs) in complex soil environments is mainly due to the improper consumption of reactive oxidative species (ROS) by non-target background substances and limited mass transfer. Herein, we developed iron sulfide (FeS) as a structurally stable heterogeneous catalyst to selectively and continuously generate ROS via peroxydisulfate (PDS) activation. Synthesized FeS demonstrated exceptional PDS activation, achieving 95.44% carbamazepine (CBZ) removal, with high resistance to coexisting soil substances and strong pH tolerance. Mechanistic studies confirmed that CBZ degradation was driven by surface-bound SO4•- radicals and singlet oxygen (1O2). The presence of sulfide species in FexSy significantly enhanced the electrochemical performance of the catalyst, accelerating the Fe(III)/Fe(II) cycle. The results suggested that oxidation of target pollutants occurs near the soil surface rather than in bulk solution, reducing the mass transfer distance and improving ROS utilization. Two degradation pathways for CBZ were proposed, resulting in a considerable reduction in CBZ toxicity, and the oxidation system has little effect on the soil matrix. Heterogeneous surface oxidation demonstrates stronger oxidative capacity, electron transfer, and mass-transfer efficiency in comparison to homogeneous systems, suggesting its significant potential for remediating EOCs in soil throughout a broad pH range.