pharmacodynamic

药效学
  • 文章类型: Journal Article
    背景:下腰痛是骨质疏松症最常见的症状之一。疼痛会严重影响患者的情绪和生活质量,还会进一步加重骨丢失,造成严重的社会负担。米诺膦酸盐是需要每日给药的口服双膦酸盐。它显着降低了骨转换标志物(BTM)的水平,并迅速改善了骨质疏松症患者的腰背痛症状。骨质疏松需要长期治疗,和每日剂量降低患者的依从性。米诺膦酸盐具有比其他双膦酸盐更好的安全性。该试验的目的是探讨米诺膦酸钠治疗绝经后骨质疏松症患者腰背痛的有效性和安全性。
    方法:这是一个单中心,随机化,为期24周的开放标签对照试验.将72名符合条件的患者随机分为4组。受试者将以1:1的比例随机分配,每天接受米诺膦酸盐(1mg/天)或阿仑膦酸盐(10mg/天);高级女性(≥75岁)和老年女性(<75岁)的比例为1:2。主要结果是视觉模拟量表(VAS)评分从基线下降≥10所需的时间。次要结果是VAS评分相对于基线的变化,抢救药物的频率和剂量,BTMs,骨矿物质密度(BMD),与基线相比,上消化道(GI)症状评分的变化(包括胃灼热,疼痛,和腹胀)。
    结论:本研究将为米诺膦酸钠的有效性和安全性提供客观证据。此外,这将有助于评估不同年龄骨质疏松患者BTM与BMD之间的定量关系。
    背景:本研究方案已于2022年12月8日在ClinicalTrials.govIDNCT05645289(https://clinicaltrials.gov/search?term=NCT05645289)注册。注册名称为北京大学第三医院。本研究方案经北京大学第三医院医学科学研究伦理委员会(M2022465,2022.08.09,V2.0)审查批准。结果将发表在科学同行评审的期刊上。
    方法:该方案已在ClinicalTrials.gov注册(注册号:NCT05645289)。招聘已于2023年1月开始,目前仍在进行中。
    BACKGROUND: Low back pain is one of the most common symptoms of osteoporosis. The pain can seriously affect patients\' mood and quality of life; it can also further aggravate bone loss, causing a serious social burden. Minodronate is an oral bisphosphonate that needs to be administered daily. It significantly reduces levels of bone turnover markers (BTMs) and rapidly improves symptoms of low back pain in patients with osteoporosis. Osteoporosis requires long-term treatment, and daily dosing reduces patient compliance. Minodronate has a better safety profile than other bisphosphonates. The objective of the trial is to explore the efficacy and safety of minodronate in the treatment of low back pain in postmenopausal osteoporosis patients.
    METHODS: This is a single-centre, randomized, open-label controlled trial with a 24-week duration. Seventy-two eligible patients will be randomly divided into 4 groups. Subjects will be randomized at a 1:1 ratio to receive either minodronate (1 mg/day) or alendronate (10 mg/day) every day; senior women (≥ 75 years old) and older women (< 75 years old) will be at a ratio of 1:2. The primary outcome is the time required for the visual analogue scale (VAS) score to decline by ≥ 10 from baseline. The secondary outcome is the changes in VAS scores from baseline, the frequency and dosage of rescue medication, BTMs, bone mineral density (BMD), and variations in upper gastrointestinal (GI) symptom scores from baseline (including heartburn, pain, and bloating).
    CONCLUSIONS: This study will provide objective evidence for the efficiency and safety of minodronate. Furthermore, it will be helpful to evaluate the quantitative relationship between BTMs and BMD in patients with osteoporosis under different ages.
    BACKGROUND: This study protocol has been registered with ClinicalTrials.gov ID NCT05645289 ( https://clinicaltrials.gov/search?term=NCT05645289 ) on December 8, 2022. The registry name is Peking University Third Hospital. This study protocol was reviewed and approved by the Peking University Third Hospital Medical Science Research Ethics Committee (M2022465, 2022.08.09, V2.0). The results will be published in scientific peer-reviewed journals.
    METHODS: The protocol was registered at ClinicalTrials.gov (registration number: NCT05645289). Recruitment has started in January 2023 and is still ongoing.
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  • 文章类型: Journal Article
    目的:为了表征奈多西兰在原发性高草酸尿症1型(PH1)患者中的药代动力学和药效学特征,确定有影响的协变量并确认治疗剂量。
    方法:建立了群体药代动力学(PK)/药效学(PD)(POP-PKPD)模型,以表征奈多西兰的浓度-时间过程以及对24小时尿草酸盐(Uox)的相应作用。模拟剂量以实现临床上有意义的减少儿童Uox,进行了青少年和成人PH1。
    结果:分析包括来自143名健康参与者和PH1/PH2患者的PK数据,和46例PH1患者的PD数据。NedosiranPK由具有双n传输吸收以及并行线性和非线性消除的两室模型描述。通过间接反应模型描述了奈多西兰暴露与Uox之间的关系。体重,估计的肾小球滤过率(eGFR)和疾病状态被确定为POP-PK模型的影响协变量.模拟结果支持在青少年和成人(≥12岁)中使用170mg(体重≥50kg)和136mg(体重<50kg)的奈多西兰钠的体重带给药方案,在PH1为3.5mg/kg的儿童(6-11岁)中,对于肾功能相对保留的PH1患者(eGFR≥30mL/min/1.73m2),未进行剂量调整。按照建议的给药方案,PKAUC0-τ的模拟中位数倍数变化,ss是可接受的(≤1.51倍变化),所有年龄组中~71%的PH1患者在第52周时达到接近正常的Uox(<0.6mmol).
    结论:最终的POP-PKPD模型表征了观察到的奈多西兰PK和Uox数据。模拟支持在年龄≥6岁且肾功能相对保留的PH1患者中使用奈多西兰给药方案。
    OBJECTIVE: To characterize pharmacokinetic and pharmacodynamic profiles of nedosiran in patients with primary hyperoxaluria type 1 (PH1), identify influential covariates and confirm therapeutic doses.
    METHODS: A population pharmacokinetic (PK)/pharmacodynamic (PD) (POP-PKPD) model was developed to characterize the concentration-time course of nedosiran and the corresponding effect on 24-h urinary oxalate (Uox). Simulations of dosing to achieve clinically meaningful reduction in Uox in children, adolescents and adults with PH1 were performed.
    RESULTS: Analyses included PK data from 143 healthy participants and PH1/PH2 patients, and PD data from 46 PH1 patients. Nedosiran PK was described by a two-compartment model with dual n-transit absorption and parallel linear and nonlinear elimination. The relationship between nedosiran exposure and Uox was described by an indirect response model. Body weight, estimated glomerular filtration rate (eGFR) and disease status were identified as influential covariates for the POP-PK model. The simulation results supported a weight-banded dosing regimen of nedosiran sodium in adolescents and adults (≥12 years) with PH1 of 170 mg (weight ≥50 kg) and 136 mg (weight <50 kg), in children (6-11 years) with PH1 of 3.5 mg/kg, and no dose adjustments for PH1 patients with relatively preserved kidney function (eGFR ≥ 30 mL/min/1.73m2). Following the proposed dosing regimens, the simulated median fold-changes in PK AUC0-τ,ss were acceptable (≤1.51 fold-change) and ~71% of PH1 patients across all age groups achieved near-normal Uox (<0.6 mmol) by week 52.
    CONCLUSIONS: The final POP-PKPD model characterizes observed nedosiran PK and Uox data. Simulations support nedosiran dosing regimens in PH1 patients aged ≥6 years with relatively preserved kidney function.
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  • 文章类型: Journal Article
    兴奋剂代表注意力缺陷/多动症(ADHD)的一线药物治疗,是处方最多的精神药理学治疗方法之一。它们在突触水平上的作用机制已被广泛研究。然而,尚不清楚它们的作用机制如何决定临床观察到的益处.为了帮助弥合这个差距,我们提供了对兴奋剂作用的全面审查,重点是核医学和磁共振成像(MRI)的发现。有证据表明,兴奋剂诱导的多巴胺和去甲肾上腺素神经传递的调节优化了与任务相关的大脑网络的参与,增加感知的显著性,并减少来自默认模式网络的干扰。在任务或休息期间,急性服用兴奋剂可能会减少未经治疗的个体在前纹状体-底小脑网络中观察到的大脑变化。长期治疗的潜在影响仍存在争议。总的来说,神经影像学促进了对兴奋剂作用机制的理解。然而,研究通常受到小样本的限制,短期或无后续行动,和方法论的异质性。未来的研究应该解决与年龄相关的长期影响,兴奋剂之间的潜在差异,和治疗反应的预测因子。
    Stimulants represent the first line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) and are among the most prescribed psychopharmacological treatments. Their mechanism of action at synaptic level has been extensively studied. However, it is less clear how their mechanism of action determines clinically observed benefits. To help bridge this gap, we provide a comprehensive review of stimulant effects, with an emphasis on nuclear medicine and magnetic resonance imaging (MRI) findings. There is evidence that stimulant-induced modulation of dopamine and norepinephrine neurotransmission optimizes engagement of task-related brain networks, increases perceived saliency, and reduces interference from the default mode network. An acute administration of stimulants may reduce brain alterations observed in untreated individuals in fronto-striato-parieto-cerebellar networks during tasks or at rest. Potential effects of prolonged treatment remain controversial. Overall, neuroimaging has fostered understanding on stimulant mechanism of action. However, studies are often limited by small samples, short or no follow-up, and methodological heterogeneity. Future studies should address age-related and longer-term effects, potential differences among stimulants, and predictors of treatment response.
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  • 文章类型: Journal Article
    肉毒杆菌神经毒素(BoNT)通常用于治疗和美容应用。一种这样的神经毒素,BoNTA型(BoNT/A),已广泛研究其对肌肉功能和收缩的影响。尽管BoNT/A产品的重要性,确定这些毒素的血液浓度可能具有挑战性。为了解决这个问题,研究人员专注于药效学(PD)标记,包括复合肌肉动作电位(CMAP)和手指外展评分(DAS)。在这项研究中,我们的目的是建立一个概率动力学-药效学(K-PD)模型,以解释BoNT/A产品开发过程中从小鼠和大鼠获得的CMAP和DAS数据.研究人员还希望更好地了解模型中的估计参数如何与动物模型与人类反应的桥接有关。我们使用雌性癌症研究所小鼠和Sprague-Dawley(SD)大鼠在施用BoNT/A后32周内测量CMAP和DAS水平。我们使用虚拟药代动力学(PK)室结合间接反应模型开发了肌肉收缩抑制模型,并使用拟合优度分析进行了模型诊断。视觉预测检查(VPC),和引导分析。CMAP和DAS曲线呈剂量依赖性,恢复时间取决于给药剂量。最终的K-PD模型有效地表征了数据,并提供了对PK和PD参数中物种特异性差异的见解。总的来说,这项研究证明了PK-PD模型在理解BoNT/A的作用方面的实用性,并为其他BoNT/A产品的未来研究提供了基础。
    Botulinum neurotoxins (BoNTs) are commonly used in therapeutic and cosmetic applications. One such neurotoxin, BoNT type A (BoNT/A), has been studied widely for its effects on muscle function and contraction. Despite the importance of BoNT/A products, determining the blood concentrations of these toxins can be challenging. To address this, researchers have focused on pharmacodynamic (PD) markers, including compound muscle action potential (CMAP) and digit abduction scoring (DAS). In this study, we aimed to develop a probabilistic kinetic-pharmacodynamic (K-PD) model to interpret CMAP and DAS data obtained from mice and rats during the development of BoNT/A products. The researchers also wanted to gain a better understanding of how the estimated parameters from the model relate to the bridging of animal models to human responses. We used female Institute of Cancer Research mice and Sprague-Dawley (SD) rats to measure CMAP and DAS levels over 32 weeks after administering BoNT/A. We developed a muscle-contraction inhibition model using a virtual pharmacokinetic (PK) compartment combined with an indirect response model and performed model diagnostics using goodness-of-fit analysis, visual predictive checks (VPC), and bootstrap analysis. The CMAP and DAS profiles were dose-dependent, with recovery times varying depending on the administered dose. The final K-PD model effectively characterized the data and provided insights into species-specific differences in the PK and PD parameters. Overall, this study demonstrated the utility of PK-PD modeling in understanding the effects of BoNT/A and provides a foundation for future research on other BoNT/A products.
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  • 文章类型: Journal Article
    抑肽酶是人类蛋白酶的广谱抑制剂,由于其有效的抗纤维蛋白溶解作用,已被批准用于治疗单冠状动脉搭桥手术中的出血。在COVID-19大流行爆发后,迫切需要寻找新的抗病毒药物。抑肽酶是治疗性重新定位作为广谱抗病毒药物和治疗特征病毒性呼吸道疾病的症状过程的良好候选者。包括COVID-19。这是由于其强大的药理学能力,可以抑制呼吸道病毒在其感染机制中使用的过多宿主蛋白酶。蛋白酶允许组成其病毒衣壳的蛋白质的切割和构象变化,从而使它们能够通过识别上皮细胞中的靶标来锚定自己。此外,这些蛋白酶的激活会引发引发感染的炎症过程。药物的吸引力不仅在于其药效学特征,还在于通过吸入途径给药的可能性,避免不必要的系统性影响。这个,加上治疗费用低(约2欧元/剂),使其成为到达经济能力较低的国家的一个很好的候选人。在这篇文章中,我们将讨论药效学,药代动力学,和通过吸入途径给药的抑肽酶的毒理学特征;分析我们对这种药物的认识的主要进展;以及为了在治疗中重新定位这种药物在研究中应该采取的未来方向。
    Aprotinin is a broad-spectrum inhibitor of human proteases that has been approved for the treatment of bleeding in single coronary artery bypass surgery because of its potent antifibrinolytic actions. Following the outbreak of the COVID-19 pandemic, there was an urgent need to find new antiviral drugs. Aprotinin is a good candidate for therapeutic repositioning as a broad-spectrum antiviral drug and for treating the symptomatic processes that characterise viral respiratory diseases, including COVID-19. This is due to its strong pharmacological ability to inhibit a plethora of host proteases used by respiratory viruses in their infective mechanisms. The proteases allow the cleavage and conformational change of proteins that make up their viral capsid, and thus enable them to anchor themselves by recognition of their target in the epithelial cell. In addition, the activation of these proteases initiates the inflammatory process that triggers the infection. The attraction of the drug is not only its pharmacodynamic characteristics but also the possibility of administration by the inhalation route, avoiding unwanted systemic effects. This, together with the low cost of treatment (≈2 Euro/dose), makes it a good candidate to reach countries with lower economic means. In this article, we will discuss the pharmacodynamic, pharmacokinetic, and toxicological characteristics of aprotinin administered by the inhalation route; analyse the main advances in our knowledge of this medication; and the future directions that should be taken in research in order to reposition this medication in therapeutics.
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  • 文章类型: Journal Article
    我们试图评估β-内酰胺抗菌药物对临床相关革兰氏阳性和革兰氏阴性病原体的多微生物群落的药效学。
    两个粪肠球菌分离株,两个金黄色葡萄球菌分离株,在静态时间杀伤实验中评估了三种具有不同β-内酰胺酶产量的大肠杆菌分离株。将每个革兰氏阳性分离物暴露于氨苄青霉素的浓度阵列(E.粪肠)或头孢唑啉(S.金黄色葡萄球菌)单独和与β-内酰胺酶缺陷的大肠杆菌分离物共培养期间,产生TEM-1,或产生KPC-3/TEM-1B。使用整合的药代动力学/药效学分析以及数学建模来总结时间杀伤实验的结果,以充分表征抗菌药效学。
    在综合分析中,在单培养实验或与β-内酰胺酶缺陷型大肠杆菌共培养期间,氨苄西林对两个粪肠球菌分离株的最大杀灭率(Emax)≥4.11,而在与产β-内酰胺酶的大肠杆菌共培养期间,Emax降低至≤1.54。与单一文化实验相比,用产生KPC的大肠杆菌培养金黄色葡萄球菌导致头孢唑啉Emax分别从3.25和3.71降低至2.02和2.98。创建两个数学模型来描述大肠杆菌与粪肠球菌或金黄色葡萄球菌之间的相互作用。当与大肠杆菌共培养时,金黄色葡萄球菌的头孢唑啉Kmax降低了24.8%(23.1%RSE)。同样,产β-内酰胺酶的大肠杆菌优先保护耐氨苄青霉素的粪肠球菌亚群,降低Kmax,r下降90.1%(14%RSE)。
    产生β-内酰胺酶的大肠杆菌能够保护金黄色葡萄球菌和粪肠球菌免于暴露于β-内酰胺抗菌剂。
    UNASSIGNED: We sought to evaluate the pharmacodynamics of β-lactam antibacterials against polymicrobial communities of clinically relevant gram-positive and gram-negative pathogens.
    UNASSIGNED: Two Enterococcus faecalis isolates, two Staphylococcus aureus isolates, and three Escherichia coli isolates with varying β-lactamase production were evaluated in static time-killing experiments. Each gram-positive isolate was exposed to a concentration array of ampicillin (E. faecalis) or cefazolin (S. aureus) alone and during co-culture with an E. coli isolate that was β-lactamase-deficient, produced TEM-1, or produced KPC-3/TEM-1B. The results of the time-killing experiments were summarized using an integrated pharmacokinetic/pharmacodynamics analysis as well as mathematical modelling to fully characterize the antibacterial pharmacodynamics.
    UNASSIGNED: In the integrated analysis, the maximum killing of ampicillin (Emax) against both E. faecalis isolates was ≥ 4.11 during monoculture experiments or co-culture with β-lactamase-deficient E. coli, whereas the Emax was reduced to ≤ 1.54 during co-culture with β-lactamase-producing E. coli. In comparison to monoculture experiments, culturing S. aureus with KPC-producing E. coli resulted in reductions of the cefazolin Emax from 3.25 and 3.71 down to 2.02 and 2.98, respectively. Two mathematical models were created to describe the interactions between E. coli and either E. faecalis or S. aureus. When in co-culture with E. coli, S. aureus experienced a reduction in its cefazolin Kmax by 24.8% (23.1%RSE). Similarly, β-lactamase-producing E. coli preferentially protected the ampicillin-resistant E. faecalis subpopulation, reducing Kmax,r by 90.1% (14%RSE).
    UNASSIGNED: β-lactamase-producing E. coli were capable of protecting S. aureus and E. faecalis from exposure to β-lactam antibacterials.
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  • 文章类型: Journal Article
    目的:本研究旨在确定充氧器对包括Quadrox-i充氧器在内的当代新生儿/儿科(1/4英寸)和青少年/成人(3/8英寸)体外膜-氧合(ECMO)回路中瑞德西韦(RDV)改变的影响。
    方法:四分之一英寸和3/8英寸,用Quadrox-i儿科和Quadrox-i成人充氧器和血液灌注准备模拟闭环ECMO回路。此外,还制备了1/4英寸和3/8英寸的电路,没有串联的充氧器。将1次剂量的RDV施用到回路中,并在0至5分钟时获得连续的预充氧剂和充氧剂浓度,1-,2-,3-,4-,5-,6-,8-,12-,和24小时的时间点。还将RDV保持在玻璃小瓶中,并且在相同的时间段从小瓶中取样用于对照目的以评估自发的药物降解。
    结果:对于带充氧器的1/4英寸电路,在研究期间有35%至60%的RDV损失。对于没有充氧器的1/4英寸电路,在研究期间有5%至20%的RDV损失。对于带和不带充氧器的3/8英寸电路,在研究期间有60%至70%的RDV损失。
    结论:在研究期间,电路内存在RDV损失,与1/4英寸电路相比,较大的3/8英寸电路RDV损失更明显。-氧合器对RDV损失的影响似乎是可变的,并且可能取决于电路和-氧合器的大小。这些初步数据表明,可能需要调整RDV剂量,以考虑通过ECMO回路的药物损失。需要额外的单剂量和多剂量研究来验证这些发现。
    OBJECTIVE: This study aimed to determine the oxygenator impact on alterations of remdesivir (RDV) in a contemporary neonatal/pediatric (1/4-inch) and adolescent/adult (3/8-inch) extracorporeal membrane -oxygenation (ECMO) circuit including the Quadrox-i oxygenator.
    METHODS: One-quarter-inch and a 3/8-inch, simulated closed-loop ECMO circuits were prepared with a Quadrox-i pediatric and Quadrox-i adult oxygenator and blood primed. Additionally, 1/4-inch and 3/8-inch circuits were also prepared without an oxygenator in series. A 1-time dose of RDV was administered into the circuits and serial preoxygenator and postoxygenator concentrations were obtained at 0 to 5 minutes, and 1-, 2-, 3-, 4-, 5-, 6-, 8-, 12-, and 24-hour time points. The RDV was also maintained in a glass vial and samples were taken from the vial at the same time periods for control purposes to assess for spontaneous drug degradation.
    RESULTS: For the 1/4-inch circuits with an oxygenator, there was a 35% to 60% RDV loss during the study period. For the 1/4-inch circuits without an oxygenator, there was a 5% to 20% RDV loss during the study period. For the 3/8-inch circuit with and without an oxygenator, there was a 60% to 70% RDV loss during the study period.
    CONCLUSIONS: There was RDV loss within the circuit during the study period and the RDV loss was more pronounced with the larger 3/8-inch circuit when compared with the 1/4-inch circuit. The impact of the -oxygenator on RDV loss appears to be variable and possibly dependent on the size of the circuit and -oxygenator. These preliminary data suggest RDV dosing may need to be adjusted for concern of drug loss via the ECMO circuit. Additional single- and multiple-dose studies are needed to validate these findings.
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  • 文章类型: Journal Article
    可拆卸的溶解微针(DDMN)的特征在于能够在施用期间与基片分离的针阵列。在这里,它们被制造以解决胰岛素的递送效率和储存稳定性。构建的胰岛素-DDMN是多层的,1)硬尖端覆盖层;2)与透明质酸(HA)和山梨糖醇(Sor)混合的常规短效胰岛素(RI)层,其占据针的锥形尖端区域;3)位于RI层上方的屏障层;和4)将屏障层连接至基片的快速溶解层。包埋在DDMN中的RI表现出增强的热稳定性;它可以在40°C下储存35天,而不会失去明显的生物活性。差示扫描量热分析表明,HA-Sor基质可以将RI的变性温度从低于室温提高到186°C。离体猪皮肤中的测试表明RI递送效率为91±1.59%。对糖尿病大鼠的实验显示RI的持续释放,即,与相同RI剂量的皮下注射相比,RI-DDMNs使胰岛素吸收到血液循环中较慢,降血糖作用的延迟发作,更长的血清胰岛素半衰期,和更长的低血糖持续时间。
    The detachable dissolving microneedles (DDMNs) feature an array of needles capable of being separated from the base sheet during administration. Here they were fabricated to address delivery efficiency and storage stability of insulin. The constructed insulin-DDMN is multi-layered, with 1) a hard tip cover layer; 2) a layer of regular short-acting insulin (RI) mixed with hyaluronic acid (HA) and sorbitol (Sor) which occupies the taper tip region of the needles; 3) a barrier layer situated above the RI layer; and 4) a fast-dissolving layer connecting the barrier layer to the base sheet. RI entrapped in DDMNs exhibited enhanced thermal stability; it could be stored at 40 °C for 35 days without losing significant biological activity. Differential scanning calorimetric analysis revealed that the HA-Sor matrix could improve the denaturation temperature of the RI from lower than room temperature to 186 °C. Tests in ex vivo porcine skin demonstrated RI delivery efficiency of 91±1.59 %. Experiments with diabetic rats revealed sustained release of RI, i.e., when compared to subcutaneous injection with the same RI dose, RI-DDMNs produced slower absorption of insulin into blood circulation, delayed onset of hypoglycemic effect, longer serum insulin half-life, and longer hypoglycemic duration.
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  • 文章类型: Journal Article
    背景:根据世界卫生组织,世界上80%以上的人口依赖传统医学。传统医学通常基于使用单一草药或多草药制剂(PHF)来管理疾病。然而,这些制剂可能的作用方式没有得到很好的研究或记录。在过去的几十年里,计算方法已被用于研究单一草药中植物化学物质的分子机制。然而,用于研究PHFs的计算机模拟方法尚不清楚。
    目的:本方案的目的是为范围审查制定一种搜索策略,以绘制用于了解全球用作传统药物的PHFs活性的计算机模拟方法。
    方法:范围审查将根据Arksey和O\'Malley开发的方法以及JoannaBriggs研究所(JBI)的建议进行。一组预定关键字将用于从五个数据库中识别相关研究:PubMed,Embase,科学直接,WebofScience,谷歌学者。两名独立审稿人将根据纳入和排除标准进行搜索,以得出相关研究的列表。Mendeley版本1.19.8将用于删除重复引用,标题和摘要筛选将与Rayyan软件进行。统一管理的JBI系统,评估,和信息审查工具将用于数据提取。范围审查将根据PRISMA-ScR(系统审查的首选报告项目和范围审查的荟萃分析扩展)指南进行报告。
    结果:根据范围审查的核心领域,开发了三步搜索策略。最初的搜索产生了3865项研究。应用过滤器后,875项研究入围进一步审查。进一步完善了关键词,以产生关于该主题的更多相关研究。
    结论:这些发现有望确定在PHF中计算方法应用于世界各地任何传统医学的知识差距的程度。该研究可以为与PHFs的植物化学鉴定相关的开放研究问题提供答案,目标识别标准,应用于计算机模拟研究的策略,使用的软件,以及采用计算机方法了解PHF作用机制的挑战。因此,这项研究可以更好地了解用于研究PHF的计算机模拟方法的应用和类型。
    PRR1-10.2196/56646。
    BACKGROUND: According to the World Health Organization, more than 80% of the world\'s population relies on traditional medicine. Traditional medicine is typically based on the use of single herbal drugs or polyherbal formulations (PHFs) to manage diseases. However, the probable mode of action of these formulations is not well studied or documented. Over the past few decades, computational methods have been used to study the molecular mechanism of phytochemicals in single herbal drugs. However, the in silico methods applied to study PHFs remain unclear.
    OBJECTIVE: The aim of this protocol is to develop a search strategy for a scoping review to map the in silico approaches applied in understanding the activity of PHFs used as traditional medicines worldwide.
    METHODS: The scoping review will be conducted based on the methodology developed by Arksey and O\'Malley and the recommendations of the Joanna Briggs Institute (JBI). A set of predetermined keywords will be used to identify the relevant studies from five databases: PubMed, Embase, Science Direct, Web of Science, and Google Scholar. Two independent reviewers will conduct the search to yield a list of relevant studies based on the inclusion and exclusion criteria. Mendeley version 1.19.8 will be used to remove duplicate citations, and title and abstract screening will be performed with Rayyan software. The JBI System for the Unified Management, Assessment, and Review of Information tool will be used for data extraction. The scoping review will be reported based on the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines.
    RESULTS: Based on the core areas of the scoping review, a 3-step search strategy was developed. The initial search produced 3865 studies. After applying filters, 875 studies were short-listed for further review. Keywords were further refined to yield more relevant studies on the topic.
    CONCLUSIONS: The findings are expected to determine the extent of the knowledge gap in the applications of computational methods in PHFs for any traditional medicine across the world. The study can provide answers to open research questions related to the phytochemical identification of PHFs, criteria for target identification, strategies applied for in silico studies, software used, and challenges in adopting in silico methods for understanding the mechanisms of action of PHFs. This study can thus provide a better understanding of the application and types of in silico methods for investigating PHFs.
    UNASSIGNED: PRR1-10.2196/56646.
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  • 文章类型: Journal Article
    精神病学中的多药是对药物-药物相互作用和治疗挑战的深入检查,探索了精神病学多药的复杂景观,一种涉及为精神健康障碍患者开具多种药物的做法。这篇综述基于药物-药物相互作用的关键方面和相关的治疗挑战。精神病学的多重用药是由心理健康状况的复杂性引起的,单一疗法可能不足。虽然它提供了潜在的好处,这种做法引起了与可能损害安全性和有效性的药物相互作用相关的担忧.该综述深入研究了精神病多重用药的患病率和临床适应症,彻底分析药物相互作用,治疗挑战,和缓解策略。实际案例研究说明了管理复杂药物治疗方案的复杂性和结果,虽然个性化医疗的新兴趋势,精神药理学的进步,多学科方法,和数字健康解决方案提供了对精神科多重用药的未来一瞥。这项检查强调了以病人为中心的重要性,基于证据的方法来优化精神病多重用药,以实现治疗益处,同时将风险降至最低。
    Polypharmacy in psychiatry is an in-depth examination of drug-drug interactions and treatment challenges that explores the intricate landscape of psychiatric polypharmacy, a practice involving the prescription of multiple medications to individuals with mental health disorders. This review is based on the critical aspects of drug-drug interactions and the associated treatment challenges. Psychiatric polypharmacy is motivated by the complexity of mental health conditions, where monotherapy may be insufficient. While it offers potential benefits, the practice raises concerns related to drug interactions that can compromise safety and efficacy. The review delves into the prevalence and clinical indications for psychiatric polypharmacy, thoroughly analyzing drug interactions, treatment challenges, and strategies for mitigation. Real-world case studies illustrate the complexities and outcomes of managing complex medication regimens, while emerging trends in personalized medicine, advancements in psychopharmacology, multidisciplinary approaches, and digital health solutions offer a glimpse into the future of psychiatric polypharmacy. This examination underscores the importance of a patient-centered, evidence-based approach in optimizing psychiatric polypharmacy to achieve therapeutic benefits while minimizing risks.
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