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1.
Rev. esp. patol ; 57(2): 133-136, Abr-Jun, 2024. ilus
Artigo em Espanhol | IBECS | ID: ibc-232419

RESUMO

La esofagitis disecante superficial (EDS) es una entidad infrecuente que se caracteriza endoscópicamente por el desprendimiento de las capas superficiales del epitelio esofágico e, histológicamente, por el aspecto bitonal del epitelio escamoso esofágico secundario a la necrosis de los estratos más superficiales. La etiología es desconocida, aunque se ha asociado con la ingesta de determinados fármacos, enfermedades autoinmunes, estasis esofágica y procedimientos endoscópicos. Presentamos dos casos: uno de ellos acontece en una mujer tras un episodio de disfagia abrupta y el segundo en un varón con comorbilidades y clínica de dolor epigástrico. La EDS es una patología que hay que considerar en su adecuado contexto clínico y endoscópico, ya que su curso es autolimitado en comparación con otras entidades de evolución tórpida o que precisan un tratamiento específico. (AU)


Esophagitis dissecans superficialis (EDS) is a rare disease characterized by sloughing of the superficial esophageal mucosa and, histologically, by the bitonal appearance of the squamous epithelium secondary to necrosis of the most superficial layers. Etiology is uncertain, however, it has been associated with some medications, autoimmune diseases, esophageal stasis and endoscopic procedures. Here, two cases are presented, one of them which appeared in a woman after an episode of dysphagia and another one which occurred to a man with comorbidities and epigastric pain. This entity should be considered due to its self-limiting clinical course, compared to other entities with a more torpid evolution or that require more specific treatment. (AU)


Assuntos
Humanos , Esofagite , Preparações Farmacêuticas , Doenças Autoimunes , Endoscopia Gastrointestinal , Comorbidade
2.
J Mass Spectrom ; 59(5): e5029, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38656528

RESUMO

Over the past three decades, mass spectrometry imaging (MSI) has emerged as a valuable tool for the spatial localization of drugs and metabolites directly from tissue surfaces without the need for labels. MSI offers molecular specificity, making it increasingly popular in the pharmaceutical industry compared to conventional imaging techniques like quantitative whole-body autoradiography (QWBA) and immunohistochemistry, which are unable to distinguish parent drugs from metabolites. Across the industry, there has been a consistent uptake in the utilization of MSI to investigate drug and metabolite distribution patterns, and the integration of MSI with omics technologies in preclinical investigations. To continue the further adoption of MSI in drug discovery and development, we believe there are two key areas that need to be addressed. First, there is a need for accurate quantification of analytes from MSI distribution studies. Second, there is a need for increased interactions with regulatory agencies for guidance on the utility and incorporation of MSI techniques in regulatory filings. Ongoing efforts are being made to address these areas, and it is hoped that MSI will gain broader utilization within the industry, thereby becoming a critical ingredient in driving drug discovery and development.


Assuntos
Descoberta de Drogas , Espectrometria de Massas , Descoberta de Drogas/métodos , Espectrometria de Massas/métodos , Humanos , Animais , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/metabolismo , Preparações Farmacêuticas/química , Desenvolvimento de Medicamentos/métodos , Imagem Molecular/métodos
3.
J Med Chem ; 67(8): 6508-6518, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38568752

RESUMO

Computational models that predict pharmacokinetic properties are critical to deprioritize drug candidates that emerge as hits in high-throughput screening campaigns. We collected, curated, and integrated a database of compounds tested in 12 major end points comprising over 10,000 unique molecules. We then employed these data to build and validate binary quantitative structure-activity relationship (QSAR) models. All trained models achieved a correct classification rate above 0.60 and a positive predictive value above 0.50. To illustrate their utility in drug discovery, we used these models to predict the pharmacokinetic properties for drugs in the NCATS Inxight Drugs database. In addition, we employed the developed models to predict the pharmacokinetic properties of all compounds in the DrugBank. All models described in this paper have been integrated and made publicly available via the PhaKinPro Web-portal that can be accessed at https://phakinpro.mml.unc.edu/.


Assuntos
Relação Quantitativa Estrutura-Atividade , Humanos , Internet , Descoberta de Drogas , Preparações Farmacêuticas/metabolismo , Preparações Farmacêuticas/química
4.
J Korean Med Sci ; 39(14): e134, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622939

RESUMO

The global research and pharmaceutical community rapidly mobilized to develop treatments for coronavirus disease 2019 (COVID-19). Existing treatments have been repurposed and new drugs have emerged. Here we summarize mechanisms and clinical trials of COVID-19 therapeutics approved or in development. Two reviewers, working independently, reviewed published data for approved COVID-19 vaccines and drugs, as well as developmental pipelines, using databases from the following organizations: United States Food and Drug Administration (US-FDA), European Medicines Agency (EMA), Japanese Pharmaceutical and Medical Devices Agency (PMDA), and ClinicalTrials.gov. In all, 387 drugs were found for initial review. After removing unrelated trials and drugs, 66 drugs were selected, including 17 approved drugs and 49 drugs under development. These drugs were classified into six categories: 1) drugs targeting the viral life cycle 2) Anti-severe acute respiratory syndrome coronavirus 2 Monoclonal Antibodies, 3) immunomodulators, 4) anti-coagulants, 5) COVID-19-induced neuropathy drugs, and 6) other therapeutics. Among the 49 drugs under development are the following: 6 drugs targeting the viral life cycle, 12 immunosuppression drugs, 2 immunostimulants, 2 HIF-PHD targeting drugs, 3 GM-CSF targeting drugs, 5 anti-coagulants, 2 COVID-19-induced neuropathy drugs, and 17 others. This review provides insight into mechanisms of action, properties, and indications for COVID-19 medications.


Assuntos
COVID-19 , Estados Unidos , Humanos , SARS-CoV-2 , Vacinas contra COVID-19/uso terapêutico , Antivirais/uso terapêutico , Antivirais/farmacologia , Anticorpos Antivirais , Preparações Farmacêuticas
5.
J Chromatogr A ; 1722: 464866, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38581976

RESUMO

The detection of aromatic aldehydes, considered potential genotoxic impurities, holds significant importance during drug development and production. Current analytical methods necessitate complex pre-treatment processes and exhibit insufficient specificity and sensitivity. This study presents the utilization of naphthalenediimide as a pre-column derivatisation reagent to detect aromatic aldehyde impurities in pharmaceuticals via high-performance liquid chromatography (HPLC). We screened a series of derivatisation reagents through density functional theory (DFT) and investigated the phenomenon of photoinduced electron transfer (PET) for both the derivatisation reagents and the resulting products. Optimal experimental conditions for derivatisation were achieved at 40 °C for 60 min. This approach has been successfully applied to detect residual aromatic aldehyde genotoxic impurities in various pharmaceutical preparations, including 4-Nitrobenzaldehyde, 2-Nitrobenzaldehyde, 1,4-Benzodioxane-6-aldehyde, and 5-Hydroxymethylfurfural. The pre-column derivatisation method significantly enhanced detection sensitivity and reduced the limit of detection (LOD), which ranged from 0.002 to 0.008 µg/ml for the analytes, with relative standard deviations < 3 %. The correlation coefficient (R2) >0.998 demonstrated high quality. In chloramphenicol eye drops, the concentration of 4-Nitrobenzaldehyde was measured to be 8.6 µg/mL below the specified concentration, with recoveries ranging from 90.0 % to 119.2 %. In comparison to existing methods, our work simplifies the pretreatment process, enhances the sensitivity and specificity of the analysis, and offers comprehensive insights into impurity detection in pharmaceutical preparations.


Assuntos
Aldeídos , Contaminação de Medicamentos , Imidas , Limite de Detecção , Naftalenos , Cromatografia Líquida de Alta Pressão/métodos , Naftalenos/química , Naftalenos/análise , Aldeídos/análise , Aldeídos/química , Imidas/química , Mutagênicos/análise , Mutagênicos/química , Preparações Farmacêuticas/química , Preparações Farmacêuticas/análise , Benzaldeídos/química , Benzaldeídos/análise
6.
Drug Ther Bull ; 62(5): 66, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38594061
7.
Nature ; 628(8007): 320-325, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38600268

RESUMO

Force-controlled release of small molecules offers great promise for the delivery of drugs and the release of healing or reporting agents in a medical or materials context1-3. In polymer mechanochemistry, polymers are used as actuators to stretch mechanosensitive molecules (mechanophores)4. This technique has enabled the release of molecular cargo by rearrangement, as a direct5,6 or indirect7-10 consequence of bond scission in a mechanophore, or by dissociation of cage11, supramolecular12 or metal complexes13,14, and even by 'flex activation'15,16. However, the systems described so far are limited in the diversity and/or quantity of the molecules released per stretching event1,2. This is due to the difficulty in iteratively activating scissile mechanophores, as the actuating polymers will dissociate after the first activation. Physical encapsulation strategies can be used to deliver a larger cargo load, but these are often subject to non-specific (that is, non-mechanical) release3. Here we show that a rotaxane (an interlocked molecule in which a macrocycle is trapped on a stoppered axle) acts as an efficient actuator to trigger the release of cargo molecules appended to its axle. The release of up to five cargo molecules per rotaxane actuator was demonstrated in solution, by ultrasonication, and in bulk, by compression, achieving a release efficiency of up to 71% and 30%, respectively, which places this rotaxane device among the most efficient release systems achieved so far1. We also demonstrate the release of three representative functional molecules (a drug, a fluorescent tag and an organocatalyst), and we anticipate that a large variety of cargo molecules could be released with this device. This rotaxane actuator provides a versatile platform for various force-controlled release applications.


Assuntos
Preparações de Ação Retardada , Rotaxanos , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/química , Polímeros/química , Rotaxanos/química , Preparações Farmacêuticas/química , Corantes Fluorescentes/química
8.
J Chromatogr A ; 1722: 464830, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38608366

RESUMO

Development of meaningful and reliable analytical assays in the (bio)pharmaceutical industry can often be challenging, involving tedious trial and error experimentation. In this work, an automated analytical workflow using an AI-based algorithm for streamlined method development and optimization is presented. Chromatographic methods are developed and optimized from start to finish by a feedback-controlled modeling approach using readily available LC instrumentation and software technologies, bypassing manual user intervention. With the use of such tools, the time requirement of the analyst is drastically minimized in the development of a method. Herein key insights on chromatography system control, automatic optimization of mobile phase conditions, and final separation landscape for challenging multicomponent mixtures are presented (e.g., small molecules drug, peptides, proteins, and vaccine products) showcased by a detailed comparison of a chiral method development process. The work presented here illustrates the power of modern chromatography instrumentation and AI-based software to accelerate the development and deployment of new separation assays across (bio)pharmaceutical modalities while yielding substantial cost-savings, method robustness, and fast analytical turnaround.


Assuntos
Software , Cromatografia Líquida/métodos , Algoritmos , Peptídeos/análise , Peptídeos/química , Proteínas/análise , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/química , Inteligência Artificial , Vacinas/química , Vacinas/análise , Retroalimentação
9.
Nat Commun ; 15(1): 3349, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637496

RESUMO

Catalysed C-H activation has emerged as a transformative platform for molecular synthesis and provides new opportunities in drug discovery by late-stage functionalisation (LSF) of complex molecules. Notably, small aliphatic motifs have gained significant interest in medicinal chemistry for their beneficial properties and applications as sp3-rich functional group bioisosteres. In this context, we disclose a versatile strategy with broad applicability for the ruthenium-catalysed late-stage meta-C(sp2)-H alkylation of pharmaceuticals. This general protocol leverages numerous directing groups inherently part of bioactive scaffolds to selectivity install a variety of medicinally relevant bifunctional alkyl units within drug compounds. Our strategy enables the direct modification of unprotected lead structures to quickly generate an array of pharmaceutically useful analogues without resorting to de novo syntheses. Moreover, productive late-stage modulation of key biological characteristics of drug candidates upon remote C-H alkylation proves viable, highlighting the major benefits of our approach to offer in drug development programmes.


Assuntos
Hidrogênio , Rutênio , Hidrogênio/química , Alquilação , Rutênio/química , Catálise , Preparações Farmacêuticas
10.
BMC Med ; 22(1): 166, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38637816

RESUMO

BACKGROUND: The co-administration of drugs known to interact greatly impacts morbidity, mortality, and health economics. This study aims to examine the drug-drug interaction (DDI) phenomenon with a large-scale longitudinal analysis of age and gender differences found in drug administration data from three distinct healthcare systems. METHODS: This study analyzes drug administrations from population-wide electronic health records in Blumenau (Brazil; 133 K individuals), Catalonia (Spain; 5.5 M individuals), and Indianapolis (USA; 264 K individuals). The stratified prevalences of DDI for multiple severity levels per patient gender and age at the time of administration are computed, and null models are used to estimate the expected impact of polypharmacy on DDI prevalence. Finally, to study actionable strategies to reduce DDI prevalence, alternative polypharmacy regimens using drugs with fewer known interactions are simulated. RESULTS: A large prevalence of co-administration of drugs known to interact is found in all populations, affecting 12.51%, 12.12%, and 10.06% of individuals in Blumenau, Indianapolis, and Catalonia, respectively. Despite very different healthcare systems and drug availability, the increasing prevalence of DDI as patients age is very similar across all three populations and is not explained solely by higher co-administration rates in the elderly. In general, the prevalence of DDI is significantly higher in women - with the exception of men over 50 years old in Indianapolis. Finally, we show that using proton pump inhibitor alternatives to omeprazole (the drug involved in more co-administrations in Catalonia and Blumenau), the proportion of patients that are administered known DDI can be reduced by up to 21% in both Blumenau and Catalonia and 2% in Indianapolis. CONCLUSIONS: DDI administration has a high incidence in society, regardless of geographic, population, and healthcare management differences. Although DDI prevalence increases with age, our analysis points to a complex phenomenon that is much more prevalent than expected, suggesting comorbidities as key drivers of the increase. Furthermore, the gender differences observed in most age groups across populations are concerning in regard to gender equity in healthcare. Finally, our study exemplifies how electronic health records' analysis can lead to actionable interventions that significantly reduce the administration of known DDI and its associated human and economic costs.


Assuntos
Polimedicação , Masculino , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Preparações Farmacêuticas , Prevalência , Interações Medicamentosas , Comorbidade
11.
PLoS One ; 19(4): e0302177, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38640114

RESUMO

BACKGROUND: Older adults with polypharmacy are more prone to medication errors. People with low educational attainment have more difficulties in taking their medications. OBJECTIVES: This study aimed to identify the extent of medication self-administration errors (MSEs) and the contributing factors among illiterate and low-literate community-dwelling older adults with polypharmacy. METHOD: The present cross-sectional study was conducted among people aged 60 and above. The data were collected using the sociodemographic, clinical, and Belief about Medicines Questionnaires (BMQ). To determine the extent of MSE, a medication error checklist was used. The negative binomial hierarchical regression model in the five blocks was performed. RESULTS: The final sample size was 276 people. The frequency of MSEs in the last 6 months was 69.2%. Sixteen percent of participants had made four or more mistakes. The most common MSEs were forgetting, improper taking of medications with food, improper timing, incorrect dosage (lower dose), and forgetting the doctor's instructions. Near 18% of participants reported adverse events following their mistakes. The significant predictors of MSEs were being completely illiterate (p = 0.021), the higher number of doctor visits per year (p = 0.014), irregularly seeing doctors (p < .001), the higher number of medications (p < .001), and having poor medication beliefs (p < .001). CONCLUSION: Despite the high prevalence of MSEs among older patients, practical strategies to deal with them at their homes have not been established among health systems. MSE as a multifactorial event can be caused by a collection of internal and external factors. Further studies to identify the role of patients, clinicians, procedures, and systems in developing MSEs as interconnected components are needed.


Assuntos
Vida Independente , Polimedicação , Humanos , Idoso , Estudos Transversais , Erros de Medicação , Preparações Farmacêuticas
12.
Sci Rep ; 14(1): 9074, 2024 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643204

RESUMO

Serious hematological adverse drug reactions (HADRs) may lead to or prolong hospitalization and even cause death. The aim of this study was to determine the regulatory factors associated with HADRs caused by drugs that were authorized up to July 2023 by the European Medicines Agency (EMA) and to evaluate the frequency of HADRs. Using a cross-sectional approach, the type and frequency of HADRs were collected from the Summaries of Product Characteristics of Drugs Authorized by the EMA and analyzed within proprietary, nonproprietary, and biosimilar/biological frameworks. Multivariate statistical analysis was used to investigate the associations of generic status, biosimilar status, conditional approval, exceptional circumstances, accelerated assessment, orphan drug status, years on the market, administration route, and inclusion on the Essential Medicines List (EML) with HADRs. In total, 54.78% of proprietary drugs were associated with HADRs at any frequency, while anemia, leucopenia, and thrombocytopenia were observed in approximately 36% of the patients. The predictors of any HADR, anemia, and thrombocytopenia of any frequency are generic status, biosimilar status, and inclusion on the EML, while the only protective factor is the administration route. Biosimilars and their originator biologicals have similar frequencies of HADRs; the only exception is somatropin. Knowledge of the regulatory factors associated with HADRs could help clinicians address monitoring issues when new drugs are introduced for the treatment of patients.


Assuntos
Anemia , Medicamentos Biossimilares , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medicamentos Essenciais , Leucopenia , Trombocitopenia , Humanos , Preparações Farmacêuticas , Medicamentos Biossimilares/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Medicamentos Genéricos , Trombocitopenia/induzido quimicamente , Leucopenia/induzido quimicamente , Anemia/induzido quimicamente , Anemia/tratamento farmacológico , Aprovação de Drogas
13.
Bull Environ Contam Toxicol ; 112(5): 67, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38668895

RESUMO

To date, there is an increased risk to public health and the environment due to the presence of pharmaceutically active compounds within drinking water supply and distribution networks. Owing to this, a direct injection-HPLC/MS-MS method was developed for the simultaneous determination of 16 active pharmaceutical compounds in tap water samples: amoxicillin, ampicillin, cephalexin, cefotaxime, cefuroxime, ciprofloxacin, clarithromycin, clindamycin, chloramphenicol, cyproterone, erythromycin, flutamide, spironolactone, sulfamethoxazole, tamoxifen, and trimethoprim. Limits of detection (LOD) ranged from 0.2 to 6.0 µg/L while quantification limits (LOQ) from 0.3 to 20 µg/L. Recovery percentages were between 70 and 125%. Total analysis time was short, with all compounds being resolved in less than 2.1 min. Of the 22 tap water samples collected and analyzed, the highest concentrations corresponded to amoxicillin (147 µg/L) and ciprofloxacin (44 µg/L). The findings could set a precedent for establishing safe levels of these compounds and increasing standards for tap water quality in this region.


Assuntos
Água Potável , Monitoramento Ambiental , Espectrometria de Massas em Tandem , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Cromatografia Líquida de Alta Pressão , Água Potável/química , Monitoramento Ambiental/métodos , Preparações Farmacêuticas/análise , Limite de Detecção , Ciprofloxacina/análise , Abastecimento de Água , Amoxicilina/análise
14.
Pol Merkur Lekarski ; 52(2): 216-225, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38642358

RESUMO

OBJECTIVE: Aim: To study changes of dental biofilm microbiota composition during experimental opioid exposure, after its withdrawal and when using of complex drug correction.. PATIENTS AND METHODS: Materials and Methods: Microbiological studies (48 rats) included microscopic and bacteriological methods, as well as determination of antibiotic susceptibility of microbial isolates. Ceftriaxone and pentoxifylline were used to correction the changes. RESULTS: Results: The action of opioid for 10 weeks caused considerable changes in the microbiocenosis, which was illustrated by a significant increasing of the opportunistic pathogens quantitative indicators and the emergence of pathogenic microbiota. Changes in the microbiocenosis at 6 weeks of opioid exposure and after its withdrawal for 4 weeks were expressed in the appearance of pathogenic microbiota and the absence of significant differences in quantitative indicators of saprophytic and opportunistic microflora compared to similar indicators in animals with 10 weeks opioid exposure. This indicated a slow progression of dysbiotic changes and the inflammatory process in the oral cavity of rats. CONCLUSION: Conclusions: After 10 weeks of experiment with opioid administration for 6 weeks and the use of ceftriaxone and pentoxifylline on the background of 4-week opioid withdrawal, a significant reduction of quantitative indicators of opportunistic bacteria and elimination of pathogenic species of microorganisms was determined. The use of complex drug correction on the background of 10 weeks of opioid exposure led to a significant reduction in the quantitative indicators of opportunistic pathogens and contributed to the elimination of most pathogenic species of microbiota under the action of ceftriaxone.


Assuntos
Microbiota , Pentoxifilina , Ratos , Animais , Analgésicos Opioides/efeitos adversos , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Preparações Farmacêuticas , Pentoxifilina/farmacologia , Pentoxifilina/uso terapêutico
15.
AAPS PharmSciTech ; 25(4): 74, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575778

RESUMO

Advancements in recombinant DNA technology have made proteins and peptides available for diagnostic and therapeutic applications, but their effectiveness when taken orally leads to poor patient compliance, requiring clinical administration. Among the alternative routes, transmucosal delivery has the advantage of being noninvasive and bypassing hepato-gastrointestinal clearance. Various mucosal routes-buccal, nasal, pulmonary, rectal, and vaginal-have been explored for delivering these macromolecules. Nanofibers, due to their unique properties like high surface-area-to-volume ratio, mechanical strength, and improved encapsulation efficiency, serve as promising carriers for proteins and peptides. These nanofibers can be tailored for quick dissolution, controlled release, enhanced encapsulation, targeted delivery, and improved bioavailability, offering superior pharmaceutical and pharmacokinetic performance compared to conventional methods. This leads to reduced dosages, fewer side effects, and enhanced patient compliance. Hence, nanofibers hold tremendous potential for protein/peptide delivery, especially through mucosal routes. This review focuses on the therapeutic application of proteins and peptides, challenges faced in their conventional delivery, techniques for fabricating different types of nanofibers and, various nanofiber-based dosage forms, and factors influencing nanofiber generation. Insights pertaining to the precise selection of materials used for fabricating nanofibers and regulatory aspects have been covered. Case studies wherein the use of specific protein/peptide-loaded nanofibers and delivered via oral/vaginal/nasal mucosa for diagnostic/therapeutic use and related preclinical and clinical studies conducted have been included in this review.


Assuntos
Sistemas de Liberação de Medicamentos , Nanofibras , Feminino , Humanos , Sistemas de Liberação de Medicamentos/métodos , Nanofibras/química , Proteínas , Peptídeos , Preparações Farmacêuticas
16.
Sci Total Environ ; 926: 172146, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38569963

RESUMO

Anthropogenic activities have led to the emergence of pharmaceutical pollution in marine ecosystems, posing a significant threat to biodiversity in conjunction with global climate change. While the ecotoxicity of human drugs on aquatic organisms is increasingly recognized, their interactions with environmental factors, such as temperature, remain understudied. This research investigates the physiological effects of the selective serotonin reuptake inhibitor (SSRI), fluoxetine, on two diatom species, Phaeodactylum tricornutum and Thalassiosira weissflogii. Results demonstrate that fluoxetine significantly reduces growth rate and biomass production, concurrently affecting pigment contents and the thermal performance curve (TPC) of the diatoms. Fluoxetine reduces the synthesis of chlorophyll a (Chl a) and carotenoid (Car), indicating inhibition of photosynthesis and photoprotection. Furthermore, fluoxetine decreases the maximum growth rate (µmax) while increasing the optimum temperature (Topt) in both species, suggesting an altered thermal plasticity. This shift is attributed to the observed decrease in the inhibition rate of fluoxetine with rising temperatures. These findings emphasize the physiological impacts and ecological implications of fluoxetine on phytoplankton and underscore the significance of considering interactions between multiple environmental drivers when accessing the ecotoxicity of potential pollutants. The present study provides insights into crucial considerations for evaluating the impacts of pharmaceutical pollution on marine primary producers.


Assuntos
Diatomáceas , Humanos , Diatomáceas/fisiologia , Clorofila A , Fluoxetina/toxicidade , Temperatura , Ecossistema , Preparações Farmacêuticas
17.
J Am Heart Assoc ; 13(8): e034506, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38606773

RESUMO

BACKGROUND: Clinical practice guidelines (CPGs) offer disease management recommendations based on scientific evidence. However, financial conflicts of interest between CPG developers and the pharmaceutical industry could bias these recommendations, potentially affecting patient care. Proper management of these conflicts of interest is particularly crucial for maintaining the integrity of CPGs. The study aimed to evaluate the extent of financial relationships between the pharmaceutical industry and authors of CPGs for cardiovascular diseases in Japan. METHODS AND RESULTS: The study analyzed personal payments from the pharmaceutical industry to authors of cardiovascular disease CPGs published by the Japanese Circulation Society from January 2015 to December 2022. Payment data, including speaking, consultancy, and writing fees from 2016 to 2020, were extracted from a publicly available database containing personal payments disclosed by all major pharmaceutical companies. A total of 929 unique authors from 37 eligible Japanese Circulation Society CPGs were identified. Notably, 94.4% of these authors received personal payments from pharmaceutical companies, totaling >US $70.8 million. The mean±SD payment per author was US $76 314±138 663) and the median payment per author was US $20 792 (interquartile range: US $4262-US $76 998) over the 5-year period. Chairs of CPGs received significantly higher payments than other authors. More than 80% of authors in each CPG received personal payments. CONCLUSIONS: The study elucidated that there were considerable financial relationships between pharmaceutical companies and cardiology CPG authors in Japan. This finding deviates from international conflict of interest management policies, suggesting the need for more stringent conflict of interest management strategies by the Japanese Circulation Society to ensure the development of trustworthy and evidence-based CPGs.


Assuntos
Cardiologia , Doenças Cardiovasculares , Humanos , Japão , Conflito de Interesses , Apoio Financeiro , Autoria , Indústria Farmacêutica , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/terapia , Preparações Farmacêuticas
18.
J Mass Spectrom ; 59(5): e5023, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38624283

RESUMO

Microsampling has revolutionized pharmaceutical drug development and clinical research by reducing sample volume requirements, allowing sample collection at home or nontraditional sites, minimizing animal and patient burden, and enabling more flexible study designs. This perspective paper discusses the transformative impact of microsampling and patient-centric sampling (PCS) techniques, emphasizing their advantages in drug development and clinical trials. We highlight the integration of liquid chromatography-mass spectrometry (LC-MS) strategies for analyzing PCS samples, focusing on our research experience and a review of current literatures. The paper reviews commercially available PCS devices, their regulatory status, and their application in clinical trials, underscoring the benefits of PCS in expanding patient enrollment diversity and improving study designs. We also address the operational challenges of implementing PCS, including the need for bridging studies to ensure data comparability between traditional and microsampling methods, and the analytical challenges posed by PCS samples. The paper proposes future directions for PCS, including the development of global regulatory standards, technological advancements to enhance user experience, the increased concern of sustainability and patient data privacy, and the integration of PCS with other technologies for improved performance in drug development and clinical studies. By advancing microsampling and PCS techniques, we aim to foster patient-centric approaches in pharmaceutical sciences, ultimately enhancing patient care and treatment efficacy.


Assuntos
Desenvolvimento de Medicamentos , 60705 , Animais , Humanos , Projetos de Pesquisa , Assistência Centrada no Paciente , Preparações Farmacêuticas
19.
Eur J Pharm Biopharm ; 198: 114276, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38582179

RESUMO

The eye is one of the most complex organs in the human body, with a unique anatomy and physiology, being divided into anterior and posterior segments. Ocular diseases can occur in both segments, but different diseases affect different segments. Glaucoma and cataracts affect the anterior segment, while macular degeneration and diabetic retinopathy occur in the posterior segment. The easiest approach to treat ocular diseases, especially in the anterior segment, is through the administration of topical eye drops, but this route presents many constraints, namely precorneal dynamic and static ocular barriers. On the other hand, the delivery of drugs to the posterior segment of the eye is far more challenging and is mainly performed by the intravitreal route. However, it can lead to severe complications such as retinal detachment, endophthalmitis, increased intraocular pressure and haemorrhage. The design of new drug delivery systems for the anterior segment is very challenging, but targeting the posterior one is even more difficult and little progress has been made. In this review we will discuss various strategies including the incorporation of additives in the formulations, such as viscosity, permeability, and solubility enhancers, namely based on Deep eutectic systems (DES). Natural deep eutectic systems (NADES) have emerged to solve several problems encountered in pharmaceutical industry, regarding the pharmacokinetic and pharmacodynamic properties of drugs. NADES can contribute to the design of advanced technologies for ocular therapeutics, including hydrogels and nanomaterials. Here in, we revise some applications of (NA)DES in the development of new drug delivery systems that can be translated into the ophthalmology field.


Assuntos
Oftalmopatias , Degeneração Macular , Humanos , Olho/metabolismo , Oftalmopatias/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Degeneração Macular/tratamento farmacológico
20.
Ophthalmologie ; 121(4): 333-348, 2024 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-38587538

RESUMO

The use of ophthalmic agents during pregnancy and breastfeeding always represents an off-label use. Therefore, the use of drugs must be particularly carefully assessed with respect to the risk-benefit assessment. In this overview the literature databank of the PubMed library, pharmaceutical lists (Red List, Swiss pharmaceutical compendium), guidelines of the specialist societies the German Society of Ophthalmology (DOG), the Swiss Society of Ophthalmology (SOG), the European Glaucoma Society (EGS), the American Academy of Ophthalmology (AAO) and internet portals (embryotox, reprotox) were inspected and recommendations for the use of ophthalmic agents during pregnancy and breastfeeding were derived. More attention should be dedicated to this topic in the specialist societies.


Assuntos
Glaucoma , Oftalmologia , Feminino , Humanos , Gravidez , Academias e Institutos , Glaucoma/tratamento farmacológico , Preparações Farmacêuticas , Sociedades Médicas , Estados Unidos
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