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1.
J Environ Sci (China) ; 148: 399-408, 2025 Feb.
Article in English | MEDLINE | ID: mdl-39095175

ABSTRACT

A mixed oxidant of chlorine dioxide (ClO2) and NaClO was often used in water treatment. A novel UVA-LED (365 nm)-activated mixed ClO2/NaClO process was proposed for the degradation of micropollutants in this study. Carbamazepine (CBZ) was selected as the target pollutant. Compared with the UVA365/ClO2 process, the UVA365/ClO2/NaClO process can improve the degradation of CBZ, with the rate constant increasing from 2.11×10-4 sec-1 to 2.74×10-4 sec-1. In addition, the consumption of oxidants in the UVA365/ClO2/NaClO process (73.67%) can also be lower than that of UVA365/NaClO (86.42%). When the NaClO ratio increased, both the degradation efficiency of CBZ and the consumption of oxidants can increase in the UVA365/ClO2/NaClO process. The solution pH can affect the contribution of NaClO in the total oxidant ratio. When the pH range of 6.0-8.0, the combination process can generate more active species to promote the degradation of CBZ. The change of active species with oxidant molar ratio was investigated in the UVA365/ClO2/NaClO process. When ClO2 acted as the main oxidant, HO• and Cl• were the main active species, while when NaClO was the main oxidant, ClO• played a role in the system. Both chloride ion (Cl-), bicarbonate ion (HCO3-), and nitrate ion (NO3-) can promote the reaction system. As the concentration of NaClO in the reaction solution increased, the generation of chlorates will decrease. The UVA365/ClO2/NaClO process can effectively control the formation of volatile disinfection by-products (DBPs), and with the increase of ClO2 dosage, the formation of DBPs can also decrease.


Subject(s)
Carbamazepine , Chlorine Compounds , Oxides , Ultraviolet Rays , Water Pollutants, Chemical , Water Purification , Carbamazepine/chemistry , Water Pollutants, Chemical/chemistry , Chlorine Compounds/chemistry , Water Purification/methods , Oxides/chemistry , Kinetics , Sodium Hypochlorite/chemistry , Models, Chemical
2.
JAMA Netw Open ; 7(8): e2425593, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39115847

ABSTRACT

Importance: Precise estimation of a patient's drug metabolism capacity is important for antiseizure dose personalization. Objective: To quantify the differences in plasma concentrations for antiseizure drugs associated with variants of genes encoding drug metabolizing enzymes. Data Sources: PubMed, Clinicaltrialsregister.eu, ClinicalTrials.gov, International Clinical Trials Registry Platform, and CENTRAL databases were screened for studies from January 1, 1990, to September 30, 2023, without language restrictions. Study Selection: Two reviewers performed independent study screening and assessed the following inclusion criteria: appropriate genotyping was performed, genotype-based categorization into subgroups was possible, and each subgroup contained at least 3 participants. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed for data extraction and subsequent quality, validity, and risk-of-bias assessments. The results from the included studies were pooled with random-effect meta-analysis. Main Outcomes and Measures: Plasma concentrations of antiseizure drugs were quantified with the dose-normalized area under the concentration-time curve, the dose-normalized steady state concentration, or the concentrations after a single dose at standardized dose and sampling time. The ratio of the means was calculated by dividing the mean drug plasma concentrations of carriers and noncarriers of the pharmacogenetic variant. Results: Data from 98 studies involving 12 543 adult participants treated with phenytoin, valproate, lamotrigine, or carbamazepine were analyzed. Studies were mainly conducted within East Asian (69 studies) or White or European (15 studies) cohorts. Significant increases of plasma concentrations compared with the reference subgroup were observed for phenytoin, by 46% (95% CI, 33%-61%) in CYP2C9 intermediate metabolizers, 20% (95% CI, 17%-30%) in CYP2C19 intermediate metabolizers, and 39% (95% CI, 24%-56%) in CYP2C19 poor metabolizers; for valproate, by 12% (95% CI, 4%-20%) in CYP2C9 intermediate metabolizers, 12% (95% CI, 2%-24%) in CYP2C19 intermediate metabolizers, and 20% (95% CI, 2%-41%) in CYP2C19 poor metabolizers; and for carbamazepine, by 12% (95% CI, 3%-22%) in CYP3A5 poor metabolizers. Conclusions and Relevance: This systematic review and meta-analysis found that CYP2C9 and CYP2C19 genotypes encoding low enzymatic capacity were associated with a clinically relevant increase in phenytoin plasma concentrations, several pharmacogenetic variants were associated with statistically significant but only marginally clinically relevant changes in valproate and carbamazepine plasma concentrations, and numerous pharmacogenetic variants were not associated with statistically significant differences in plasma concentrations of antiseizure drugs.


Subject(s)
Anticonvulsants , Pharmacogenomic Variants , Humans , Anticonvulsants/pharmacokinetics , Anticonvulsants/blood , Anticonvulsants/therapeutic use , Valproic Acid/blood , Valproic Acid/therapeutic use , Valproic Acid/pharmacokinetics , Adult , Female , Carbamazepine/therapeutic use , Carbamazepine/blood , Male , Epilepsy/drug therapy , Epilepsy/genetics , Epilepsy/blood , Cytochrome P-450 CYP2C19/genetics , Phenytoin/blood , Phenytoin/therapeutic use , Phenytoin/pharmacokinetics , Genotype , Lamotrigine/blood , Lamotrigine/therapeutic use , Pharmacogenetics , Cytochrome P-450 CYP2C9/genetics
3.
J Pharmacol Toxicol Methods ; 128: 107536, 2024.
Article in English | MEDLINE | ID: mdl-38972615

ABSTRACT

Standardization and validation of in vitro drug metabolism is essential for pre-clinical drug development as well as for in vitro toxicity assays including the lymphocyte toxicity assay (LTA) and the in vitro platelet toxicity assay (iPTA). Use of isolated liver microsomes (MIC) in in vitro testing has been utilized for a long time; however, the effect of species of origin and induction agents on the metabolic capacities of MIC is not adequately evaluated. In this study we investigated the impact of species of origin and induction agent on the capacity of MICs to bioactivate carbamazepine (CBZ) using cytotoxicity as a gross endpoint to measure the levels of cytotoxic metabolites generated by each type of MICs. Jurkat E6.1 cell line was used and MICs from human, rat, mouse, minipig and rabbit origin as well as rat MICs that is either non-induced or induced by phenobarbitone (PHB), dexamethasone (DEXA), 3-methylcholanthrene (3MC), clofibrate (CLOF) and isoniazid (INH) were investigated. MICs from minipig and rat MICs induced with 3MC exhibited the highest capacity to produce cytotoxic metabolites of CBZ. These findings will help optimize and standardize in vitro toxicity assays and provide guidance to pre-clinical investigation of drugs.


Subject(s)
Carbamazepine , Microsomes, Liver , Species Specificity , Swine, Miniature , Carbamazepine/toxicity , Animals , Humans , Rats , Microsomes, Liver/drug effects , Microsomes, Liver/metabolism , Mice , Swine , Rabbits , Jurkat Cells , Toxicity Tests/methods , Anticonvulsants/toxicity , Male , Isoniazid/toxicity
4.
Clin Transl Sci ; 17(7): e13892, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39034448

ABSTRACT

JBPOS0101 is a new antiepileptic drug and is a substrate of UDP-glucuronosyltransferases (UGTs) in in vitro test. In vitro experiments showed different results regarding whether JBPOS0101 induces (EC50 136 µM) or inhibits (IC50 95.4-386.5 µM) cytochrome P450 (CYP) 3A4. As co-medication of JBPOS0101 and carbamazepine (CBZ) is expected in clinical settings, drug-drug interactions (DDIs) between them should be determined. This study aimed to investigate pharmacokinetic (PK) interactions of JBPOS0101 influenced by CYP3A4 and UGTs using midazolam (MDZ) and CBZ. A two-cohort, open-label, fixed-sequence study was conducted in healthy Koreans. In cohort A, subjects received MDZ IV alone, and then JBPOS0101 were co-administered with MDZ after oral doses of JBPOS0101 for 7 days. In cohort B, multiple doses of JBPOS0101 and CBZ were administered respectively, and subjects received both together for 7 days. Serial blood samples were collected for PK analysis. When MDZ and JBPOS0101 were co-administered, the systemic exposure of MDZ decreased by 30%. Meanwhile, JBPOS0101 did not significantly changed the PK of CBZ. CBZ decreased the systemic exposure of JBPOS0101 at steady state by 40%, respectively. With IV administration of MDZ, JBPOS0101 acted as a weak inducer of hepatic CYP3A4 and decreased systemic exposure of MDZ. The ability of JBPOS0101 to similarly modulate gut CYP3A4 activity will require further evaluation. Co-administration of multiple doses of JBPOS0101 and CBZ did not significantly alter CBZ pharmacokinetics, but the clinical impact of decreased systemic exposure of JBPOS0101 by CBZ should be further considered.


Subject(s)
Anticonvulsants , Carbamazepine , Cytochrome P-450 CYP3A , Drug Interactions , Glucuronosyltransferase , Midazolam , Humans , Cytochrome P-450 CYP3A/metabolism , Male , Adult , Carbamazepine/pharmacokinetics , Carbamazepine/administration & dosage , Glucuronosyltransferase/metabolism , Midazolam/pharmacokinetics , Midazolam/administration & dosage , Young Adult , Anticonvulsants/pharmacokinetics , Anticonvulsants/administration & dosage , Female , Healthy Volunteers , Administration, Oral
5.
Int J Mol Sci ; 25(13)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-39000059

ABSTRACT

There is growing concern about the potential ecological risks posed by pharmaceutical residues in the aquatic environment. However, our understanding of the toxic effects of antiepileptic pharmaceuticals, such as carbamazepine (CBZ), on aquatic animal larvae is still limited. In this study, the tadpoles of the black-spotted pond frog (Pelophylax nigromaculatus) were exposed to environmentally relevant concentrations of CBZ (0.3 and 3.0 µg/L) for 30 days, and their growth, intestinal microbial composition, and metabolites were investigated to assess the potential toxic effects of CBZ in non-targeted aquatic organisms. Some tadpoles died during exposure, but there was no significant among-group difference in the survival and growth rates. CBZ exposure significantly altered the composition of tadpole intestinal microbiota. Relative abundances of some bacterial genera (e.g., Blautia, Prevotella, Bacillus, Microbacterium, etc.) decreased, while others (e.g., Paucibacter, etc.) increased in CBZ-exposed tadpoles. Interestingly, CBZ-induced alterations in some bacteria might not necessarily lead to adverse outcomes for animals. Meanwhile, small molecular intestinal metabolites related to energy metabolism, and antioxidant and anti-inflammatory activities were also altered after exposure. Taken together, environmentally relevant levels of CBZ might alter the metabolic and immune performances of amphibian larvae by modifying the abundance of some specific bacteria and the level of metabolites in their intestines, thereby potentially causing a long-term effect on their fitness.


Subject(s)
Anticonvulsants , Carbamazepine , Gastrointestinal Microbiome , Larva , Water Pollutants, Chemical , Animals , Larva/drug effects , Carbamazepine/pharmacology , Gastrointestinal Microbiome/drug effects , Anticonvulsants/pharmacology , Water Pollutants, Chemical/toxicity , Bacteria/drug effects
6.
J Neurogenet ; 38(2): 41-45, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39007626

ABSTRACT

Pyruvate Dehydrogenase (PDH) E2 deficiency due to Dihydrolipoamide acetyltransferase (DLAT) mutations is a very rare condition with only nine reported cases to date. We describe a 15-year-old girl with mild intellectual disability, paroxysmal dystonia and bilateral basal ganglia signal abnormalities on brain magnetic resonance imaging (MRI). Additionally, neurophysiological, imaging, metabolic and exome sequencing studies were performed. Routine metabolite testing, and GLUT1 and PRRT2 mutation analysis were negative. A repeat brain MRI revealed 'Eye-of-the-tiger-sign'. Exome sequencing identified homozygous valine to glycine alteration at amino acid position 157 in the DLAT gene. Bioinformatic and family analyses indicated that the alteration was likely pathogenic. Patient's dystonia was responsive to low-dose carbamazepine. On weaning carbamazepine, patient developed hallucinations which resolved after carbamazepine was restarted. PDH E2 deficiency due to DLAT mutation has a more benign course compared to common forms of PDH E1 deficiency due to X-linked PDHA1 mutations. All known cases of PDH E2 deficiency due to DLAT mutations share the features of episodic dystonia and intellectual disability. Our patient's dystonia and hallucinations responded well to low-dose carbamazepine.


Subject(s)
Carbamazepine , Dystonia , Hallucinations , Humans , Female , Adolescent , Dystonia/genetics , Dystonia/drug therapy , Carbamazepine/therapeutic use , Hallucinations/genetics , Hallucinations/drug therapy , Mutation , Dihydrolipoyllysine-Residue Acetyltransferase/genetics , Intellectual Disability/genetics , Intellectual Disability/drug therapy , Anticonvulsants/therapeutic use
7.
BMJ Case Rep ; 17(7)2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39074946

ABSTRACT

SummaryShapiro's syndrome is a rare neurological disease. The triad of Shapiro's syndrome includes episodes of hyperhidrosis, hypothermia and complete/partial agenesis of the corpus callosum. We report a case of a young male who had episodic chills, increased sweating and fatigue. During these episodes, he was found to have bradycardia, hypotension and hypothermia. Clinical and neurological examinations were unremarkable. The MRI of the brain revealed agenesis of the corpus callosum. There was a good response to carbamazepine therapy.


Subject(s)
Carbamazepine , Hyperhidrosis , Hypothermia , Magnetic Resonance Imaging , Humans , Hyperhidrosis/etiology , Male , Hypothermia/complications , Carbamazepine/therapeutic use , Agenesis of Corpus Callosum/complications , Agenesis of Corpus Callosum/diagnostic imaging , Anticonvulsants/therapeutic use , Adult
8.
Environ Sci Technol ; 58(31): 13986-13994, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-38992920

ABSTRACT

Previous studies have highlighted the toxicity of pharmaceuticals and personal care products (PPCPs) in plants, yet understanding their spatial distribution within plant tissues and specific toxic effects remains limited. This study investigates the spatial-specific toxic effects of carbamazepine (CBZ), a prevalent PPCP, in plants. Utilizing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), CBZ and its transformation products were observed predominantly at the leaf edges, with 2.3-fold higher concentrations than inner regions, which was confirmed by LC-MS. Transcriptomic and metabolic analyses revealed significant differences in gene expression and metabolite levels between the inner and outer leaf regions, emphasizing the spatial location's role in CBZ response. Notably, photosynthesis-related genes were markedly downregulated, and photosynthetic efficiency was reduced at leaf edges. Additionally, elevated oxidative stress at leaf edges was indicated by higher antioxidant enzyme activity, cell membrane impairment, and increased free fatty acids. Given the increased oxidative stress at the leaf margins, the study suggests using in situ Raman spectroscopy for early detection of CBZ-induced damage by monitoring reactive oxygen species levels. These findings provide crucial insights into the spatial toxicological mechanisms of CBZ in plants, forming a basis for future spatial toxicology research of PPCPs.


Subject(s)
Carbamazepine , Carbamazepine/toxicity , Plant Leaves/drug effects , Oxidative Stress , Multiomics
9.
Sci Total Environ ; 948: 174739, 2024 Oct 20.
Article in English | MEDLINE | ID: mdl-39009142

ABSTRACT

The risk assessment of an expanding array of emerging contaminants in aquatic ecosystems and the establishment of water quality criteria rely on species sensitivity distribution (SSD), necessitating ample multi-trophic toxicity data. Computational methods, such as quantitative structure-activity relationship (QSAR), enable the prediction of specific toxicity data, thus mitigating the need for costly experimental testing and exposure risk assessment. In this study, robust QSAR models for four aquatic species (Rana pipiens, Crassostrea virginica, Asellus aquaticus, and Lepomis macrochirus) were developed using leave-one-out (LOO) screening variables and the partial least squares algorithm to predict toxicity data for paraquat, bisphenol A, and carbamazepine. These predicted data can be integrated with experimental data to construct SSD models and derive hazardous concentration for 5 % of species (HC5) for the criterion maximum concentration. The chronic water quality criterion for paraquat, bisphenol A, and carbamazepine were determined at 6.7, 11.1, and 3.5 µg/L, respectively. The QSAR-SSD approach presents a viable and cost-effective method for deriving water quality criteria for other emerging contaminants.


Subject(s)
Benzhydryl Compounds , Carbamazepine , Paraquat , Phenols , Quantitative Structure-Activity Relationship , Water Pollutants, Chemical , Water Quality , Phenols/toxicity , Benzhydryl Compounds/toxicity , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/analysis , Carbamazepine/toxicity , Paraquat/toxicity , Animals , Risk Assessment , Copepoda/drug effects
10.
Waste Manag ; 187: 128-133, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39029406

ABSTRACT

Pharmaceuticals have been detected at high concentrations in landfill leachate and refuse, which may pose potential long-term environmental impacts. The interaction of pharmaceuticals between leachate and refuse contributes to their retention through in situ sorption, thereby mitigating this impact. However, limited efforts have been made to describe the distribution characteristics of pharmaceuticals in the refuse-leachate phase. In this study, two refuse and three leachate samples were used to obtain partitioning coefficients (Kd) for two typical pharmaceuticals, carbamazepine (CBZ) and sulfadiazine (SD), with campus soil as a comparison. Landfill refuse exhibited higher Kd values (12.36 ± 0.90 and 19.76 ± 1.96 mL/g for CBZ and 1.90 ± 0.34 and 6.27 ± 0.58 mL/g for SD in two samples, respectively) than campus soil (3.73 ± 1.31 mL/g for CBZ and 0.81 ± 0.26 mL/g for SD), influenced by refuse properties such as higher organic matter (OM) content and specific surface area (SSA). The influence of leachate pH on Kd values depended on the electrostatic interaction between the species of target pollutants and negatively charged refuse. The effect of humic acid (HA) was related to its binding with target pollutants in solution and its competition with them for sorption sites. Electrostatic repulsion, hydrogen bonding and π-π interaction were the proposed mechanisms in SD sorption on refuse, while hydrogen bonding participated in the sorption of CBZ. The results will help aid the understanding of the distribution of pharmaceuticals in the refuse-leachate system and improve corresponding management strategies.


Subject(s)
Carbamazepine , Sulfadiazine , Waste Disposal Facilities , Water Pollutants, Chemical , Carbamazepine/chemistry , Sulfadiazine/chemistry , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/analysis , Refuse Disposal/methods , Adsorption , Soil/chemistry
11.
ACS Appl Mater Interfaces ; 16(27): 34973-34987, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38918892

ABSTRACT

A peroxymonosulfate oxidation system was developed via modification of ß-cyclodextrin (ß-CD) on the surface of Fe2+-doped ZIF-67 (CD/Fe@ZIF-67) as an activator. The 99.7% carbamazepine, 91.3% bisphenol A (BPA), and 95.4% diclofenac (DCF) degradation efficiency were achieved within 10 min, 60, and 1 min, respectively. The hydrophobicity of these three pollutants is positively correlated with their adsorption kinetic constants by CD/Fe@ZIF-67 due to the introduction of ß-CD. Scavenger experiments and electron spin resonance spectra confirmed that carbamazepine was preferentially oxidized by SO4•- [λ(SO4•-)(70.5%) > λ(•OH)(28.2%) > λ(O2•-)(1.3%)], where SO4•- and O2•- played dominant roles in the degradation of BPA [λ(SO4•-)(71.7%) > λ(O2•-)(22.8%) > λ(•OH)(5.5%)], and O2•- was responsible for DCF removal [λ(O2•-) = 93.2%]. Additionally, the particulate catalyst was immobilized in the shell side of a ceramic membrane in a membrane reactor for catalyst recovery. This reactor achieved nearly 100% removal efficiency under optimal conditions: 0.036 wt % catalyst loading, 0.5 mM peroxymonosulfate concentration, 1 L inflow, 10 mg/L initial carbamazepine concentration, and 0.012 L/min hydraulic retention time. In summary, this study elucidates the active role of ß-CD in a polymetallic/peroxymonosulfate system and provides valuable insights into the development of effective oxidation methods for pharmaceutical and personal care products in wastewater.


Subject(s)
Carbamazepine , Nanocomposites , Water Pollutants, Chemical , beta-Cyclodextrins , beta-Cyclodextrins/chemistry , Water Pollutants, Chemical/chemistry , Carbamazepine/chemistry , Nanocomposites/chemistry , Water Purification/methods , Metal-Organic Frameworks/chemistry , Benzhydryl Compounds/chemistry , Oxidation-Reduction , Phenols/chemistry , Pharmaceutical Preparations/chemistry , Diclofenac/chemistry , Adsorption , Cosmetics/chemistry , Zeolites/chemistry , Imidazoles
12.
Clin Transl Sci ; 17(6): e13867, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38894615

ABSTRACT

Genetic screening for HLA-B*15:02 before prescribing carbamazepine is standard practice to prevent severe cutaneous adverse reactions in Asian populations. These reactions are associated not only with this allele but also with closely related HLA-B75 serotype markers-HLA-B*15:11 and HLA-B*15:21-which are prevalent in several Asian countries. However, a reliable method for identifying HLA-B75 serotype markers is still not available. We developed an in-house quantitative PCR (qPCR) for HLA-B75 screening and validated it using 303 anonymized DNA samples. Due to inadequate quality control, the qPCR results for 11 samples were excluded. We analyzed the sensitivity and specificity of the test using 93 HLA-typed samples. The concordance between the qPCR method and an established screening method was assessed using 199 HLA-screened samples tested for HLA-B*15:02 at Songklanagarind Hospital, Songkhla, Thailand. All discordant results were confirmed by Sanger sequencing. The qPCR method demonstrated a sensitivity of 100% (95% confidence interval = 83.16%-100.00%) and a specificity of 100% (95% confidence interval = 95.07%-100.00%). Concordance analysis revealed a 96.5% agreement between methods (192/199; 44 positive and 148 negative results). All discordant results were due to HLA-B75 markers not being HLA-B*15:02 (two samples with HLA-B*15:11 and five samples with HLA-B*15:21). In conclusion, this qPCR method could be useful for identifying HLA-B75 carriers at risk of carbamazepine-induced reactions in Asian populations where carriers of HLA-B*15:02, HLA-B*15:11, or HLA-B*15:21 are common.


Subject(s)
Carbamazepine , HLA-B15 Antigen , Humans , Carbamazepine/adverse effects , HLA-B15 Antigen/genetics , HLA-B15 Antigen/immunology , Real-Time Polymerase Chain Reaction/methods , Thailand , Anticonvulsants/adverse effects , Asian People/genetics , Pharmacogenetics , Serogroup , Sensitivity and Specificity , Alleles
13.
Expert Rev Neurother ; 24(8): 773-786, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38870050

ABSTRACT

INTRODUCTION: Trigeminal neuralgia is a rare condition that can be effectively treated by carbamazepine or oxcarbazepine but these older drugs are associated with dose-dependent and potentially treatment-limiting adverse effects. Third-generation anticonvulsants, new calcitonin gene-related peptide blockers for migraine, and older drugs such as ketamine and cannabinoids may be promising adjuvants or monotherapeutic options. AREAS COVERED: The new drugs, their presumed mechanisms of action, safety and efficacy are discussed herein. There is a paucity of robust clinical evidence in support of these drugs for trigeminal neuralgia. New migraine agents are considered as well although migraines and trigeminal neuralgia are distinct, albeit similar, conditions. No new drugs have been released to market in recent years with the specific indication of trigeminal neuralgia. EXPERT OPINION: In real-world clinical practice, about half of trigeminal neuralgia patients take more than one agent for prevention and combination therapy may be the optimal approach. Combination therapy might allow for lower doses of carbamazepine or oxcarbazepine, thus reducing the number and severity of potential adverse events but the potential for pharmacokinetic drug-drug interactions must be considered. Drug therapy for trigeminal neuralgia involves acute or abortive treatments, often administered in hospital versus long-term preventive therapy, usually involving oral agents.


Trigeminal neuralgia is a relatively rare condition that usually affects one side of the face below the eye around the cheekbone. The cause of trigeminal neuralgia is sometimes a damaged nerve or a nerve that has lost part of its outer protective sheath (myelin). However, trigeminal neuralgia may have other neurological causes as well. Pain can be triggered by touch, pressure, or chewing and it tends to occur in very painful brief attacks followed by pauses with little or no pain. There are two types of drug treatment for trigeminal neuralgia: drugs to stop an ongoing attack (which are often administered in an emergency room or hospital intravenously) and drugs that are taken orally over the long term to reduce or prevent attacks.The two most effective drugs for trigeminal neuralgia are carbamazepine and oxcarbazepine, which are actually drugs to prevent seizures. They are effective in reducing the pain intensity and number of attacks of trigeminal neuralgia but they have side effects. In fact, these side effects can be so severe that people stop taking the drugs.Many new drugs have come to market recently that may work for trigeminal neuralgia, although none was specifically developed for this use. The newest generation of anti-seizure medications including eslicarbazepine, lacosamide, levetiracetam, and retigabine, may be just as effective as the older carbamazepine and oxcarbazepine drugs with fewer side effects. Clinical studies are needed to test them in trigeminal neuralgia patients but their mechanisms of action suggest that they might work well.There are some new drugs developed for migraine headache that inhibit a substance in the body called CGRP. Migraine headaches and trigeminal neuralgia have some of the same symptoms but they are different conditions but both involve too much CGRP.Other new drugs include lasmiditan, pimozide (used for Tourette syndrome), tizanidine (muscle relaxant), lamotrigine and vixotrigine (anti-seizure drugs) may also be beneficial. It may be that people with trigeminal neuralgia will have to take combination therapy, the use of two or more drugs with different mechanisms of action. Older drugs like ketamine and cannabinoids are also being considered as possible add-on agents for therapy for trigeminal neuralgia.


Subject(s)
Anticonvulsants , Carbamazepine , Trigeminal Neuralgia , Trigeminal Neuralgia/drug therapy , Humans , Anticonvulsants/therapeutic use , Carbamazepine/therapeutic use , Oxcarbazepine/therapeutic use , Migraine Disorders/drug therapy , Drug Therapy, Combination
14.
Environ Toxicol Chem ; 43(8): 1894-1902, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38888274

ABSTRACT

Though bioaccumulation of pharmaceuticals by aquatic organisms continues to receive scientific attention, the internal disposition of these contaminants among different tissue compartments of fish species has been infrequently investigated, particularly among fish at different trophic positions. We tested a human to fish biological read-across hypothesis for contaminant disposition by examining tissue-specific accumulation in three understudied species, longnose gar (Lepisosteus osseus; piscivore), gizzard shad (Dorosoma cepedianum; planktivore/detritivore), and smallmouth buffalo (Ictiobus bubalus; benthivore), from a river influenced by municipal effluent discharge. In addition to surface water, fish plasma, and brain, gill, gonad, liver, and lateral muscle fillet tissues were analyzed via isotope dilution liquid chromatography tandem mass spectrometry. Caffeine and sucralose, two common effluent tracers, were quantitated at low micrograms per liter levels in surface water, while an anticonvulsant, carbamazepine, was observed at levels up to 37 ng/L. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline and primary metabolites were detected in at least one tissue of all three species at low micrograms per kilogram concentrations. Within each species, brain and liver of select fish contained the highest levels of SSRIs compared to plasma and other tissues, which is generally consistent with human tissue disposition patterns. However, we observed differential accumulation among specific tissue types and species. For example, mean levels of sertraline in brain and liver tissues were 13.4 µg/kg and 1.5 µg/kg in gizzard shad and 1.3 µg/kg and 7.3 µg/kg in longnose gar, respectively. In contrast, smallmouth buffalo did not consistently accumulate SSRIs to detectable levels. Tissue-specific eco-exposome efforts are necessary to understand mechanisms associated with such marked bioaccumulation and internal dispositional differences among freshwater fish species occupying different trophic positions. Environ Toxicol Chem 2024;43:1894-1902. © 2024 The Author(s). Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Subject(s)
Fishes , Water Pollutants, Chemical , Animals , Water Pollutants, Chemical/metabolism , Water Pollutants, Chemical/pharmacokinetics , Fishes/metabolism , Bioaccumulation , Tissue Distribution , Carbamazepine/metabolism , Carbamazepine/pharmacokinetics , Sucrose/metabolism , Sucrose/analogs & derivatives , Caffeine/metabolism , Caffeine/pharmacokinetics , Liver/metabolism , Selective Serotonin Reuptake Inhibitors/metabolism , Selective Serotonin Reuptake Inhibitors/pharmacokinetics , Gills/metabolism , Environmental Monitoring , Rivers/chemistry , Food Chain , Fluoxetine/analogs & derivatives , Fluoxetine/metabolism , Fluoxetine/pharmacokinetics , Pharmaceutical Preparations/metabolism , Brain/metabolism
15.
Chemosphere ; 362: 142608, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38878981

ABSTRACT

Screening for sensitive toxicological indicators and understanding algal tolerance to pharmaceutical contaminants (PhCs) are essential for assessing PhCs risk and their removal by microalgae. Carbamazepine (CBZ) showed adverse effects on microalgae, but the specific toxicity mechanisms on the most sensitive algal photosynthetic system (PS) remain limited. This study delved into the impact of CBZ exposure on the growth, cell viability, pigment content, and PS of Chlorella vulgaris. The findings revealed a notable inhibition of C. vulgaris growth by CBZ, with an IC50 value of 27.2 mg/L at 96 h. CBZ exposure induced algal membrane damage and cell viability. Intriguingly, CBZ drastically diminished intracellular pigment levels, notably showing "low promotion and high inhibition" of chlorophyll b (Chl b) by 72 h. Moreover, the study identified a decreased number of active reaction centers (RCs) within algal PSII alongside inhibited electron transport from QA to QB on the PSII receptor side, leading to PSII disruption. As an adaptive response to CBZ stress, C. vulgaris stimulated its Chl b synthesis, increased non-photochemical quenching (NPQ), and adapted its tolerance to bright light. Additionally, the alga attempted to compensate for the CBZ-induced reduction in electron transfer efficiency at the PSII receptor side and light energy utilization by increasing its electron transfer from downstream. Principal component analysis (PCA) further verified that the parameters on non-photochemical dissipation, electron transport, and integrative performance were the most sensitive algal toxicological indicators for CBZ exposure, and algal PS has energy protection capability through negative feedback regulation. However, prolonged exposure to high doses of CBZ will eventually result in permanent damage to the algal PS. Hence, attention should be paid to the concentration of CBZ in the effluent and the exposure time, while methods to mitigate algal photodamage should be appropriately sought for algal treatment of dense effluents.


Subject(s)
Carbamazepine , Chlorella vulgaris , Chlorophyll , Photosynthesis , Photosystem II Protein Complex , Water Pollutants, Chemical , Chlorella vulgaris/drug effects , Chlorella vulgaris/metabolism , Photosynthesis/drug effects , Carbamazepine/toxicity , Water Pollutants, Chemical/toxicity , Photosystem II Protein Complex/metabolism , Chlorophyll/metabolism , Microalgae/drug effects , Electron Transport/drug effects
16.
Water Res ; 260: 121943, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38909423

ABSTRACT

Krypton chloride (KrCl*) excimer lamps (222 nm) are used as a promising irradiation source to drive ultraviolet-based advanced oxidation processes (UV-AOPs) in water treatment. In this study, the UV222/peracetic acid (PAA) process is implemented as a novel UV-AOPs for the degradation of emerging contaminants (ECs) in water. The results demonstrate that UV222/PAA process exhibits excellent degradation performance for carbamazepine (CBZ), with a removal rate of 90.8 % within 45 min. Notably, the degradation of CBZ in the UV222/PAA process (90.8 %) was significantly higher than that in the UV254/PAA process (15.1 %) at the same UV dose. The UV222/PAA process exhibits superior electrical energy per order (EE/O) performance while reducing resource consumption associated with the high-energy UV254/PAA process. Quenching experiments and electron paramagnetic resonance (EPR) detection confirm that HO• play a dominant role in the reaction. The contributions of direct photolysis, HO•, and other active species (RO• and 1O2) are estimated to be 5 %, 88 %, and 7 %, respectively. In addition, the effects of Cl-, HCO3-, and humic acid (HA) on the degradation of CBZ are evaluated. The presence of relatively low concentrations of Cl-, HCO3-, and HA can inhibit CBZ degradation. The UV222/PAA oxidation process could also effectively degrade several other ECs (i.e., iohexol, sulfamethoxazole, acetochlor, ibuprofen), indicating the potential application of this process in pollutant removal. These findings will propel the development of the UV222/PAA process and provide valuable insights for its application in water treatment.


Subject(s)
Peracetic Acid , Photolysis , Ultraviolet Rays , Water Pollutants, Chemical , Water Purification , Water Pollutants, Chemical/chemistry , Peracetic Acid/chemistry , Water Purification/methods , Carbamazepine/chemistry , Oxidation-Reduction
17.
J Environ Manage ; 362: 121331, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38833931

ABSTRACT

This study introduces an innovative LED-IoT photoreactor, representing a significant advancement in response to the demand for sustainable water purification. The integration of LED-IoT installations addresses the challenge of intermittent sunlight availability, employing LEDs with a spectrum mimicking natural sunlight. Passive Infra-Red (PIR) sensors and Internet of things (IoT) technology ensure consistent radiation intensity, with the LED deactivating in ample sunlight and activating in its absence. Utilizing a visible light-absorbing photocatalyst developed through sol-gel synthesis and mild-temperature calcination, this research demonstrates a remarkable carbamazepine removal efficiency exceeding 95% under LED-IoT system illumination, compared to less than 90% efficiency with sunlight alone, within a 6-h exposure period. Moreover, the designed photocatalytic system achieves over 60% mineralization of carbamazepine after 12 h. Notably, the photocatalyst demonstrated excellent stability with no performance loss during five further cycles. Furthermore, integration with renewable energy sources facilitated continuous operation beyond daylight hours, enhancing the system's applicability in real-world water treatment scenarios. A notable application of the LED-IoT system at an operating sewage treatment plant showed nearly 80% efficiency in carbamazepine removal from sewage in the secondary settling tank after 6 h of irradiation, coupled with nearly 40% mineralization efficiency. Additionally, physicochemical analyses such as XPS and STA-FTIR confirm that the carbamazepine photooxidation process does not affect the surface of the photocatalyst, showing no adsorption for degradation products.


Subject(s)
Carbamazepine , Solar Energy , Water Pollutants, Chemical , Water Purification , Carbamazepine/chemistry , Carbamazepine/isolation & purification , Water Purification/methods , Water Pollutants, Chemical/chemistry , Sunlight , Waste Disposal, Fluid/methods , Catalysis
18.
Actas Esp Psiquiatr ; 52(3): 375-377, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38863053

ABSTRACT

A case of Kloos syndrome is presented, a rare psychopathological manifestation in psychiatry characterized by the experience of "time paralysis" related to an epileptic focus in the left temporoparietal areas. This syndrome was identified through a detailed psychopathological analysis and detected by an electroencephalographic record. The patient's symptoms disappeared after receiving antiepileptic treatment with Carbamazepine. In this case report we highlight the detailed phenomenological and clinical analysis, as well as the importance of carrying out complementary tests when we are faced with unusual or sudden-onset symptoms without any trigger, as took place in the case exposed.


Subject(s)
Electroencephalography , Humans , Syndrome , Male , Carbamazepine/therapeutic use , Adult , Anticonvulsants/therapeutic use
19.
Math Biosci Eng ; 21(4): 5335-5359, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38872538

ABSTRACT

Trigeminal neuralgia is a debilitating condition characterized by severe facial pain. Carbamazepine has been widely used as a first-line treatment option for trigeminal neuralgia, but there is a need to evaluate its safety and efficacy based on existing evidence. This meta-analysis aims to systematically assess the available literature and provide a comprehensive evaluation of the safety and efficacy of carbamazepine in the treatment of trigeminal neuralgia. A thorough search of electronic databases yielded a total of 15 relevant studies that met the inclusion criteria. The pooled analysis of these studies revealed that carbamazepine demonstrated significant efficacy in reducing pain intensity and frequency in patients with trigeminal neuralgia. Moreover, the drug was generally well-tolerated, with the most common adverse events being mild and transient. Subgroup analyses based on different dosages and treatment durations further supported the overall findings. However, caution should be exercised in patients with certain comorbidities or specific populations, as some rare but severe adverse events were reported. In conclusion, this meta-analysis provides strong evidence supporting the safety and efficacy of carbamazepine as a valuable therapeutic option for the management of trigeminal neuralgia. These results can guide clinicians in making informed decisions regarding the use of carbamazepine and contribute to optimizing treatment strategies for patients with trigeminal neuralgia. Further research is warranted to explore long-term safety and efficacy outcomes, as well as to compare carbamazepine with alternative treatment modalities.


Subject(s)
Carbamazepine , Trigeminal Neuralgia , Humans , Analgesics, Non-Narcotic/therapeutic use , Analgesics, Non-Narcotic/adverse effects , Carbamazepine/therapeutic use , Carbamazepine/adverse effects , Treatment Outcome , Trigeminal Neuralgia/drug therapy
20.
Environ Sci Pollut Res Int ; 31(30): 42921-42930, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38880845

ABSTRACT

The viewpoints on whether high concentrations of chloride ion (Cl-) promote or inhibit the oxidation activity of activated persulfates are still inconclusive. Furthermore, the degradation of organic pollutants by the persulfates in the presence of high Cl- concentrations without any activation medium has not yet been studied. In this work, the efficiency and mechanism of degradation of organic pollutants such as carbamazepine (CBZ), sulfadiazine (SDZ), and phenol (PN) by Cl--activated PMS (denoted as Cl-/PMS) were investigated. Results showed that Cl- could effectively activate PMS for the complete removal of CBZ, SDZ, and PN with reaction kinetic constants of 0.4516 min-1, 0.01753 min-1, and 0.06805 min-1, respectively. Parameters such as PMS dose, Cl- concentration, solution pH, and initial concentrations of organic pollutants that affect the degradation efficiencies of the Cl-/PMS process were optimized. Unlike conventional activated persulfates, it was confirmed that the free chlorine was the main active species in the Cl-/PMS process. Finally, the degradation by-products of CBZ and SDZ as well as their toxicity were detected, and a possible degradation pathway for CBZ and SDZ was proposed. Though higher toxic chlorinated by-products were generated, the Cl-/PMS process was still an efficient oxidation method for the removal of organic pollutants in aqueous solutions which contain high concentrations of Cl-.


Subject(s)
Water Pollutants, Chemical , Water Pollutants, Chemical/chemistry , Oxidation-Reduction , Kinetics , Carbamazepine/chemistry
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