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1.
Nucleic Acids Res ; 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39180399

RESUMO

Drug interactions pose significant challenges in clinical practice, potentially leading to adverse drug reactions, reduced efficacy, and even life-threatening consequences. As polypharmacy becomes increasingly common, the risk of harmful drug interactions rises, underscoring the need for comprehensive and user-friendly drug interaction resources to ensure patient safety. To address these concerns and support healthcare professionals in optimizing drug therapy, we present DDInter 2.0, a significantly expanded and enhanced update to our drug interaction database. This new version incorporates additional interaction types, including drug-food interactions (DFIs), drug-disease interactions (DDSIs), and therapeutic duplications, providing a more complete resource for clinical decision-making. The updated database covers 2310 drugs, with 302 516 drug-drug interaction (DDI) records accompanied by 8398 distinct, high-quality mechanism descriptions and management recommendations. DDInter 2.0 also includes 857 DFIs, 8359 DDSIs and 6033 therapeutic duplication records, each supplemented with detailed information and guidance. Furthermore, the enhanced user interface and advanced filtering options in this second release facilitate easy access to and analysis of the comprehensive drug interaction data. By providing healthcare professionals and researchers with a more complete and user-friendly resource, DDInter 2.0 aims to support clinical decision-making and ultimately improve patient outcomes. DDInter 2.0 is freely accessible at https://ddinter2.scbdd.com.

2.
Brief Bioinform ; 24(4)2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37344167

RESUMO

Adverse drug events (ADEs) are common in clinical practice and can cause significant harm to patients and increase resource use. Natural language processing (NLP) has been applied to automate ADE detection, but NLP systems become less adaptable when drug entities are missing or multiple medications are specified in clinical narratives. Additionally, no Chinese-language NLP system has been developed for ADE detection due to the complexity of Chinese semantics, despite ˃10 million cases of drug-related adverse events occurring annually in China. To address these challenges, we propose DKADE, a deep learning and knowledge graph-based framework for identifying ADEs. DKADE infers missing drug entities and evaluates their correlations with ADEs by combining medication orders and existing drug knowledge. Moreover, DKADE can automatically screen for new adverse drug reactions. Experimental results show that DKADE achieves an overall F1-score value of 91.13%. Furthermore, the adaptability of DKADE is validated using real-world external clinical data. In summary, DKADE is a powerful tool for studying drug safety and automating adverse event monitoring.


Assuntos
Aprendizado Profundo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Reconhecimento Automatizado de Padrão , Semântica , Processamento de Linguagem Natural
3.
Int J Cancer ; 154(9): 1616-1625, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38216995

RESUMO

Anti-human epidermal growth factor receptor 2 (HER2) agents have exhibited pronounced tumor-inhibitory activity, yet the accompanying ocular toxicity has frequently been underestimated. We aim to conduct a comprehensive comparative analysis of ocular toxicity risk related to various anti-HER2 agents. We executed a retrospective pharmacovigilance investigation based on the FDA Adverse Event Reporting System (FAERS) database, covering the period from Q2 2018 to Q1 2023. The disproportionality analysis was performed to assess ocular toxicity risk. Multivariate logistic regression was implemented to mitigate potential biases. Moreover, the time to onset of ocular toxicity was also evaluated. A total of 3467 ocular adverse event (AE) reports concerning anti-HER2 agents were collected. At the preferred term (PT) level, there were 69 positive signals, among which excessive eye blinking, abnormal sensation in the eye, and asthenopia presented a significant risk. In comparison to tyrosine kinase inhibitors (TKIs), antibody drugs were associated with a broader range of ocular disorders at Standardized MedDRA Queries (SMQ)levels, including conjunctival disorders, corneal disorders, ocular infections, ocular motility disorders, optic nerve disorders, and retinal disorders. In terms of onset time, pertuzumab displayed an earlier onset at 21.5 days, while trastuzumab deruxtecan had the latest at 91.5 days. In summary, our study reveals varying degrees of ocular toxicity related to anti-HER2 agents, with a significantly higher risk observed in antibody drugs. Additionally, novel ocular toxicity signals, not documented in product labels, have been detected. In the future, further research will be necessary to validate our findings.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neuropatia Óptica Tóxica , Farmacovigilância , Estudos Retrospectivos , Bases de Dados Factuais , Sistemas de Notificação de Reações Adversas a Medicamentos
4.
Antimicrob Agents Chemother ; 68(7): e0052424, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38899917

RESUMO

HRS9432(A) is a long-acting echinocandin antifungal medication primarily used to treat invasive fungal infections, particularly invasive candidiasis. The safety, tolerability, and pharmacokinetic characteristics of HRS9432(A) injection were investigated in a randomized, double-blind, placebo-controlled, single- and multiple-ascending-dose Phase I study involving 56 healthy adult subjects. Doses ranging from 200 to 1200 mg were administered. Safety was continually monitored, including adverse events, clinical laboratory examinations, vital signs, 12-lead electrocardiograms, and physical examinations, while the pharmacokinetic profile within the body was evaluated. The results indicated that concentrations of HRS9432 peaked immediately after infusion, demonstrating essentially linear pharmacokinetic characteristics within the dosage range of 200-1,200 mg. It exhibited a low clearance rate and an extended half-life, with a clearance of approximately 0.2 L/h, a volume of distribution of around 40 L, and a half-life of approximately 140h following a single dose. The accumulation index for AUC0-τ after multiple doses ranged from 1.41 to 1.75. No severe adverse events occurred during the study, and the severity of all adverse events was mild or moderate. Therefore, the intravenous administration of HRS9432(A) in healthy Chinese adult subjects, either as multiple infusions of 200 to 600 mg (once a week, four doses) or as a single infusion of 900-1,200 mg, demonstrated overall good safety and tolerability. The pharmacokinetic exhibited essentially linear characteristics in the body, supporting a weekly dosing frequency for clinical applications and providing additional options for the treatment or prevention of invasive fungal infections. CLINICAL TRIALS: This study is registered with the International Clinical Trials Registry Platform as ChiCTR2300073525.


Assuntos
Antifúngicos , Voluntários Saudáveis , Humanos , Método Duplo-Cego , Adulto , Masculino , Antifúngicos/farmacocinética , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Feminino , Adulto Jovem , Meia-Vida , Área Sob a Curva , Micafungina/farmacocinética , Micafungina/administração & dosagem , Micafungina/efeitos adversos , Pessoa de Meia-Idade , Povo Asiático , População do Leste Asiático
5.
Brief Bioinform ; 23(2)2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35212357

RESUMO

Structural information for chemical compounds is often described by pictorial images in most scientific documents, which cannot be easily understood and manipulated by computers. This dilemma makes optical chemical structure recognition (OCSR) an essential tool for automatically mining knowledge from an enormous amount of literature. However, existing OCSR methods fall far short of our expectations for realistic requirements due to their poor recovery accuracy. In this paper, we developed a deep neural network model named ABC-Net (Atom and Bond Center Network) to predict graph structures directly. Based on the divide-and-conquer principle, we propose to model an atom or a bond as a single point in the center. In this way, we can leverage a fully convolutional neural network (CNN) to generate a series of heat-maps to identify these points and predict relevant properties, such as atom types, atom charges, bond types and other properties. Thus, the molecular structure can be recovered by assembling the detected atoms and bonds. Our approach integrates all the detection and property prediction tasks into a single fully CNN, which is scalable and capable of processing molecular images quite efficiently. Experimental results demonstrate that our method could achieve a significant improvement in recognition performance compared with publicly available tools. The proposed method could be considered as a promising solution to OCSR problems and a starting point for the acquisition of molecular information in the literature.


Assuntos
Aprendizado Profundo , Estrutura Molecular , Redes Neurais de Computação
6.
Inorg Chem ; 63(41): 19130-19139, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39353084

RESUMO

Due to the slow kinetic nature of the oxygen evolution reaction (OER), the development of electrocatalysts with high efficiency, stability, and economy for oxygen production using metal-organic framework (MOF) materials is still a challenging research topic. In this work, we chose the different concentrations of FeS adsorption to encapsulate metal cobalt-based ZIF-67 MOF for preparing a series of electrocatalysts (ZIF1FeSx, x = 0.2, 0.5, 0.75, and 1), which were mainly explored for the electrocatalytic OER. Among them, ZIF1FeS0.5 has excellent electrocatalytic activity for OER, which can be driven by low overpotentials of 276 and 349 mV at 10 and 50 mA cm-2 current densities, and more than 92% of the initial overpotential can be maintained after 100 h of continuous OER at 10 mA cm-2 current density. This is mainly due to the electronic interactions between the cobalt-based MOF and the FeS, which shift the electronic state of the active metal center to a higher valence state for increasing the number of active sites and enhancing the efficiency of electron transfer to facilitate the OER course. This work may contribute to the design of effective catalysts for the OER during the electrolysis of alkaline solutions.

7.
Inorg Chem ; 63(12): 5664-5671, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38484386

RESUMO

Metal-organic frameworks (MOFs) are considered one of the most significant electrocatalysts for the sluggish oxygen evolution reaction (OER). Hence, a series of novel N,S-codoped Ni-based heterometallic organic framework (HMOF) (NiM-bptz-HMOF, M = Co, Zn, and Mn; bptz = 2,5-bis((3-pyridyl)methylthio)thiadiazole) precatalysts are constructed by the heteroatom and second metal doping strategies. The effective combination of the two strategies promotes electronic conductivity and optimizes the electronic structure of the metal. By regulation of the type and proportion of metal ions, the electrochemical performance of the OER can be improved. Among them, the optimized Ni6Zn1-bptz-HMOF precatalyst exhibits the best performance with an overpotential of 268 mV at 10 mA cm-2 and a small Tafel slope of 72.5 mV dec-1. This work presents a novel strategy for the design of modest heteroatom-doped OER catalysts.

8.
Inorg Chem ; 63(19): 8948-8957, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38687980

RESUMO

Excellent electrocatalytic CO2 reduction reaction activity has been demonstrated by transition metals and nitrogen-codoped carbon (M-N-C) catalysts, especially for transition-metal porphyrin (MTPP)-based catalysts. In this work, we propose to use one-step low-temperature pyrolysis of the isostructural MTPP-based metal-organic frameworks (MOFs) and electrochemical in situ reduction strategies to obtain a series of hybrid catalysts of Co nanoparticles (Co NPs) and MTPP, named Co NPs/MTPP (M = Fe, Co, and Ni). The in situ introduction of Co NPs can efficiently enhance the electrocatalytic ability of MTPP (M = Fe, Co, and Ni) to convert CO2 to CO, particularly for FeTPP. Co NPs/FeTPP endowed a high CO faradaic efficiency (FECOmax = 95.5%) in the H cell, and the FECO > 90.0% is in the broad potential range of -0.72 to -1.22 VRHE. In addition, the Co NPs/FeTPP achieved 145.4 mA cm-2 at a lower potential of -0.70 VRHE with an FECO of 94.7%, and the CO partial currents increased quickly to reach 202.2 mA cm-2 at -0.80 VRHE with an FECO of 91.6% in the flow cell. It is confirmed that Co NPs are necessary for hybrid catalysts to get superior electrocatalytic activity; Co NPs also can accelerate H2O dissociation and boost the proton supply capacity to hasten the proton-coupled electron-transfer process, effectively adjusting the adsorption strength of the reaction intermediates.

9.
Inorg Chem ; 63(19): 8919-8924, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38698558

RESUMO

The introduction of transition metal (TM) ions into polyoxometalates (POMs) cannot only bring about interesting structural diversities but also enable changes in properties. However, TM-containing Silverton-type polyoxomolybdates are still lacking in terms of structural diversity and application development. Herein, two Zn(II)-containing Silverton-type {UMo12O42}-based polyoxomolybdates, H1.89Na4.11(H2O)9Zn[UMo12O42]·4.5H2O (Zn-1) and H1.8Na4.2(H2O)12Zn[UMo12O42] (Zn-2) were hydrothermally synthesized, demonstrating a practical strategy to assembly of TM-containing Silverton-type POMs. Zn-1 is proven to be an excellent and recyclable heterogeneous catalyst in cross-dehydrogenation coupling of 1,4-naphthoquinones with amines reactions, and a series of 2-amino-1,4-naphthoquinones with potential medicinal value have been constructed.

10.
Inorg Chem ; 63(26): 12240-12247, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946338

RESUMO

An unusual crystalline porous framework constructed from four types of cages, including all-inorganic Keggin-type polyoxometalate (POM) cages [H3W12O40]5-, organic hexamethylenetetramine (Hmt) cages, nanosized silver-Hmt coordination cages, and giant POM-silver-Hmt cages, was hydrothermally synthesized and structurally characterized. The framework features a highly symmetrical structure with one-dimensional nanoscale channels and holds good thermal/solvent stability, which endow it with proton conduction properties and heterogeneous catalytic activity for pyrazole. This paper not only contributes to broadening the structural diversity of cage-based crystalline porous framework materials but also sheds new light on the design of new functional framework materials.

11.
Inorg Chem ; 63(27): 12469-12474, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38912662

RESUMO

Two Mn(II)-bridged Silverton-type {UMo12O42}-based polyoxomolybdates with different three-dimensional structures, Na6(H2O)12[Mn(UMo12O42)] (NaMn) and (NH4)2[K2Na6(µ4-O)2(H2O)1.2Mn(UMo12O42)]·4.6H2O (KMn), were hydrothermally synthesized and further characterized, demonstrating a feasible strategy for the assembly of Silverton-type polyoxomolybdates. Additionally, NaMn is demonstrated to be a good heterogeneous catalyst in the condensation cyclization reaction of hydrazines and 1,3-diketones, and a range of valuable pyrazoles were produced in up to 99% yield.

12.
Inorg Chem ; 63(40): 19039-19045, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39324751

RESUMO

A unique meso Ce(III)-containing antimonotungstate, {Na(OAc)(H2O)2[Ce4(tar)(Htar)2(Sb2W21O72)2(H2O)7]}244- (Ce4tar3; H4tar = tartaric acid), consisting of two enantiomeric parts with a butterfly-like configuration, was successfully synthesized by a one-pot in situ method and characterized. The coordination of d- or l-tar ligands induced the formation of Dawson-like {Ce2Sb2W21} with right or left configurations, thereby determining the d/l configurations of {Na(OAc)(H2O)2[Ce4(tar)(Htar)2(Sb2W21O72)2(H2O)7]}22-. Carboxyl groups link these two enantiomeric parts with Ce(III) ions from each other around the symmetric center of the P1̅ space group. The three types of tar ligands exhibit distinct coordination modes, and all coordinate with at least one W(VI) atom using one carboxylate oxygen atom and one α-OH. Ce4tar3 represents the largest case among those meso-dl-tar-functionalized polyoxometalates. Furthermore, Ce4tar3 exhibits excellent catalytic activity for synthesizing isoindolinones via the three-component reaction of 2-acetylbenzoic acids, amines, and phosphine oxides.

13.
Inorg Chem ; 63(41): 19390-19395, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39350542

RESUMO

A cerium(III)-containing silicotungstate, [H2N(CH3)2]10NaK[KCe(SiW11O39)2(H2O)]·18.5H2O (CeSiW), was successfully synthesized and characterized. Structure analysis reveals that CeSiW is composed of two {SiW11O39} units connected by one cerium(III) cation to form a typical 1:2 sandwich structure, which is further expanding into a 1D chain linked by K+ ions. The oxygen-enriched surfaces of {SiW11O39} units and open cerium sites provide abundant Lewis base and acid sites in CeSiW. As a result, CeSiW efficiently catalyzed the C3-alkenylation of oxindoles with aldehydes through the simultaneous activation of both reaction substrates on its crystal framework. Various 3-benzylidene-oxindoles are synthesized with excellent yields and high E-selectivity under solvent-free conditions.

14.
Inorg Chem ; 63(32): 15134-15143, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39074382

RESUMO

Gossypol (Gsp) and antibiotics present in water bodies become organic pollutants that are harmful to human health and the ecological environment. Accurate and effective detection of these pollutants has far-reaching significance in many fields. A new three-dimensional metal-organic framework (MOF), {[Eu3(L)2(HCOO-)(H2O)3]·2H2O·2DMF}n (Eu-MOF), was synthesized from 3,5-bis(2,4-dicarboxylphenyl)nitrobenzene (H4L) ligand and Eu3+ via the solvothermal method in this paper. The Eu-MOF demonstrates strong red fluorescence and can remain stable in different pH solutions. The MOF fluorescence probe could detect organic pollutants through the "shut-off" effect, with a fast response speed and a low detection limit [Gsp, nitrofurantoin (NFT), and nitrofurazone (NFZ) for 0.43, 0.38, and 0.41 µM, respectively]. During the testing process, Eu-MOF exhibited good selectivity and recoverability. Furthermore, the mechanism of fluorescence quenching was investigated, and the recoveries were also good in real samples. This paper introduced a deep learning model to recognize the fluorescence images, a portable intelligent logic detector designed for real-time detection of Gsp by logic gate strategy, and an anticounterfeiting mark prepared based on inkjet printing. Importantly, this work provides a new way of thinking for the detection of organic pollutants in water with high sensitivity and practicality by combining the fluorescence probe with machine learning and logical judgment.


Assuntos
Antibacterianos , Európio , Corantes Fluorescentes , Gossipol , Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Európio/química , Antibacterianos/análise , Antibacterianos/química , Gossipol/análise , Gossipol/química , Poluentes Químicos da Água/análise , Nitrofuranos/análise , Espectrometria de Fluorescência , Estrutura Molecular , Limite de Detecção
15.
Inorg Chem ; 63(12): 5681-5688, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38484383

RESUMO

Three new POM-based compounds, with formulae [Na0.63Ag3(Htba)2.37(tba)0.63(H2O)2(PMo12O40)]·4H2O (Ag3PMo), [Ag4(Htba)4(H2O)2(PMo12O40)](NO3)·H2O (Ag4PMo), and [Ag3(Htba)2(tba)(PW12O40)0.5](NO3)0.5·13H2O (Ag3PW), were prepared with a 3-(4H-1,2,4-triazol-4-yl)benzoic acid (Htba) ligand, Keggin-type anions ([PMo12O40]3-/[PW12O40]3-), and a silver ion (Ag+). The structural features of these compounds are particularly different from the multinuclear subunits, which are [Ag3(tba)3] clusters in Ag3PMo, [Ag4(tba)3] chains in Ag4PMo, and [Ag3(tba)3]2 clusters in Ag3PW, connected by multidonor atom tba ligands and Ag+ ions. Meanwhile, in these compounds, polyanions act as polydentate ligands to link adjacent Ag-tba metal-organic units and expand their spatial dimensions. These compounds, as heterogeneous catalysts, exhibit high stability and excellent catalytic activity to construct benzimidazoles. Ag3PMo could efficiently catalyze the condensation of benzene-1,2-diamines and benzaldehydes and produce benzimidazoles in good yields. In addition, Ag3PMo could be reused up to 7 times and was suitable for gram-scale reactions.

16.
Org Biomol Chem ; 22(4): 784-789, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38168690

RESUMO

This paper reports a novel method for the visible-light-mediated synthesis of quinazolinones from the reaction of benzyl bromides with 2-aminobenzamides. The reaction proceeded efficiently at room temperature upon irradiation with an 18 W blue light-emitting diode in air without photocatalysts or additives. By varying the solvent type, substrate molar ratio, and reaction time, the optimal reaction conditions, including the use of methanol solvent, room temperature, and reaction time of 28 h, were identified. Under these conditions, various quinazolinones were obtained using 18 substrates, with the highest yield of 93%. To determine the industrial value of the proposed method, a scale-up reaction was performed and 80% product yield was achieved. Mechanistic studies revealed that the reaction likely proceeded via a radical pathway and that the hydrogen bromide by-product generated during the first step of the reaction of benzyl bromide with 2-aminobenzamide promoted the subsequent step.

17.
J Nanobiotechnology ; 22(1): 146, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38566213

RESUMO

Thrombotic diseases impose a significant global health burden, and conventional drug-based thrombolytic therapies are encumbered by the risk of bleeding complications. In this study, we introduce a novel drug-free nanomedicine founded on tea polyphenols nanoparticles (TPNs), which exhibits multifaceted capabilities for localized photothermal thrombolysis. TPNs were synthesized through a one-pot process under mild conditions, deriving from the monomeric epigallocatechin-3-gallate (EGCG). Within this process, indocyanine green (ICG) was effectively encapsulated, exploiting multiple intermolecular interactions between EGCG and ICG. While both TPNs and ICG inherently possessed photothermal potential, their synergy significantly enhanced photothermal conversion and stability. Furthermore, the nanomedicine was functionalized with cRGD for targeted delivery to activated platelets within thrombus sites, eliciting robust thrombolysis upon laser irradiation across diverse thrombus types. Importantly, the nanomedicine's potent free radical scavenging abilities concurrently mitigated vascular inflammation, thus diminishing the risk of disease recurrence. In summary, this highly biocompatible multifunctional nanomaterial holds promise as a comprehensive approach that combines thrombolysis with anti-inflammatory actions, offering precision in thrombosis treatment.


Assuntos
Nanomedicina , Trombose , Humanos , Polifenóis/farmacologia , Chá , Terapia Trombolítica , Verde de Indocianina/farmacologia , Verde de Indocianina/uso terapêutico , Inflamação/tratamento farmacológico , Trombose/tratamento farmacológico
18.
Clin Exp Pharmacol Physiol ; 51(1): 3-9, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37840030

RESUMO

Children, as a special group, have their own peculiarities in terms of individualized medication use compared to adults. Adverse drug reactions have been an important issue that needs to be addressed in the hope of safe medication use in children, and the occurrence of adverse drug reactions is partly due to genetic factors. Anti-infective drugs are widely used in children, and they have always been an important cause of the occurrence of adverse reactions in children. Pharmacogenomic technologies are becoming increasingly sophisticated, and there are now many guidelines describing the pharmacogenomics of anti-infective drugs. However, data from paediatric-based studies are scarce. This review provides a systematic review of the pharmacogenomics of anti-infective drugs recommended for gene-guided use in CPIC guidelines by exploring the relationship between pharmacogenetic frequencies and the incidence of adverse reactions, which will help inform future studies of individualized medication use in children.


Assuntos
Anti-Infecciosos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Adulto , Humanos , Criança , Farmacogenética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Anti-Infecciosos/efeitos adversos
19.
Lung ; 202(5): 673-681, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39191908

RESUMO

BACKGROUND: Inhaled corticosteroids (ICS) are effective in managing asthma and chronic obstructive pulmonary disease (COPD) but increase the risk of pneumonia. Benzodiazepines (BZD), commonly prescribed for comorbid psychiatric disorders in asthma or COPD patients, are also associated with pneumonia. This study investigates the risk of pneumonia associated with the concomitant use of ICS and BZD. METHODS: Data from the FDA Adverse Event Reporting System from Q4 2013 to Q3 2023 were extracted. Reports involving asthma or COPD patients were included. Disproportionality analysis and logistic regression analysis were performed to assess the risk of pneumonia associated with the combined use of ICS and BZD. Additive and multiplicative models were used to further confirm the results. Additionally, subgroup analyses were conducted based on gender, age, and disease type. RESULTS: A total of 238,411 reports were included. The combined use of ICS and BZD was associated with a higher reporting of pneumonia (ROR: 2.41, 95% CI 2.25-2.58). Using additive and multiplicative methods, the results remained significant. The strongest risk signals were observed in specific drug combinations, such as mometasone with clonazepam, budesonide with temazepam, and mometasone with zopiclone. Subgroup analyses showed higher pneumonia risks in females, patients over 60 years old, and those with asthma. CONCLUSION: Our findings identified a significantly elevated pneumonia risk with the combined use of ICS and BZD. These results highlighted the necessity for cautious co-prescription of ICS and BZD and suggested the need for more comprehensive clinical studies to assess this interaction.


Assuntos
Corticosteroides , Sistemas de Notificação de Reações Adversas a Medicamentos , Asma , Benzodiazepinas , Farmacovigilância , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Feminino , Administração por Inalação , Benzodiazepinas/efeitos adversos , Benzodiazepinas/administração & dosagem , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Pneumonia/induzido quimicamente , Asma/tratamento farmacológico , Asma/epidemiologia , Idoso , Adulto , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Estados Unidos/epidemiologia , Adulto Jovem , Adolescente , Fatores de Risco , Medição de Risco , Criança , Quimioterapia Combinada , Idoso de 80 Anos ou mais , Clonazepam/efeitos adversos , Clonazepam/administração & dosagem
20.
Skin Pharmacol Physiol ; : 1-10, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39159613

RESUMO

INTRODUCTION: Skin-blanching assay has been established as a surrogate method for assessing bioequivalence of topical corticosteroids. This study aimed to apply the skin-blanching assay to evaluate the bioequivalence of a test desonide cream (T) compared with the reference Desonide® (R) using Chinese skins. Additionally, the pharmacokinetics and safety profiles were also assessed. METHODS: By detecting the degree of skin blanching under different dose durations in a pilot dose-duration-response study, the area under the observed effect-time curve (AUEC) and half of the maximum effect (ED50) was calculated. Based on this, the skin color of different time points after a dose duration of ED50, D1 (0.5 × ED50), and D2 (2 × ED50) were detected as a pharmacodynamic indicator to compare between test and reference creams. Single-center, single-dose, randomized, open-label, two-cycle crossover pharmacokinetic studies were designed to make sure the exposure of tested formulationswas not higher than that of the reference formulations. Subjects experiencing adverse events (AEs) were monitored and utilized for safety analysis. RESULTS: These studies involved 12 subjects for the dose-duration-response study, 100 subjects for the bioequivalence study, and 12 subjects for the pharmacokinetic study. The results showed that the population ED50 was 0.88 ± 0.45 h; the mean ratio of area under effective curve from 0 to 24 h (AUEC0-24h) of test and reference preparations was 0.95, with a 90% confidence interval as 88.09-101.72%, indicating the bioequivalence of the test formulation and Desonide®. The maximum plasma concentration (Cmax) and area under the concentration time curve from time 0 to the last time point (AUC0-t) of T and R were 20.8 ± 11.5 pg/mL versus 19.7 ± 10.1 pg/mL, respectively, and 451.04 ± 363.65 pgh/mL versus 541.47 ± 581.41 pgh/mL, respectively. The systemic exposure of a single dose of the test cream was not higher than that of the reference preparation. All of the volunteers experienced grade 1 AEs, suggesting that single administration of the test desonide cream is well tolerated in the Chinese healthy population. CONCLUSIONS: This study demonstrated the applicability of skin-blanching assay in Chinese skins and established the bioequivalence of test and reference desonide creams.

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