The goal of this clinical trial is to learn if NSAIDs (i.e. naproxen sodium) can treat menstrual pain and prevent the development of chronic pelvic pain in menstruating adults with painful periods. The main questions it aims to answer are:
* Can non-menstrual pelvic pain reduction be predicted by menstrual pain response to NSAIDs?
* Will participants with the largest reductions in multi-site sensitivity following NSAID therapy have the largest reductions in non-menstrual pelvic pain?
Researchers will compare naproxen sodium to a placebo (a look-alike substance that contains no drug) to see if naproxen sodium works to treat painful periods.
Participants will:
* Take naproxen sodium or placebo during several days of their menstrual period every month for 1 year.
* Complete computer questionnaires and tests from home every 3 months.
* Complete at-home urine tests to measure hormones every few days for 1-year.
* Use a pin-prick to collect a small spot of blood, and use a pad or tampon to collect a sample of menstrual blood, and bring it to the research site twice over a 1-year period.
* Come to the research site twice over a 1-year period to complete sensory assessments and undergo a blood draw.
The major goal of the study is to develop a multivariable statistical model (see https://grants.nih.gov/grants/guide/rfa-files/RFA-NS-24-021.html ) describing the factors that effectiveness of pain medication and risk for chronic pain

开始日期2025-04-01

申办/合作机构

Endeavor Health

[+3]

IRCT20230202057310N13

/ Recruiting临床1期IIT

Comparative effects of curcumin and naproxen gels with ultrasound-enhanced delivery for cervical myofascial pain treatment

开始日期2025-01-04

申办/合作机构-

IRCT20130313012810N44

/ CompletedN/A

Comparative bioequivalence study of the Naproxen 500 mg Delayed- Release tablets manufactured by Daana Pharma Company vs Naprosyn® tablets manufactured by Recipharm Pharmaceutical Company in healthy volunteers.

开始日期2024-12-25

申办/合作机构

Daana Pharmaceutical Co.

100 项与萘普生相关的临床结果

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100 项与萘普生相关的转化医学

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100 项与萘普生相关的专利（医药）

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16,169

项与萘普生相关的文献（医药）

2025-06-01·Journal of Hazardous Materials

Stereoselective behavior of naproxen chiral enantiomers in promoting horizontal transfer of antibiotic resistance genes

Article

作者: Liu, Yu ; Zhang, Yi ; Wang, Yingying ; Li, Shuhan ; Huang, Pan ; Bartlam, Mark

Antibiotic resistance poses a global threat to public health, with recent studies highlighting the role of non-antibiotic pharmaceuticals in the transmission of antibiotic resistance genes (ARGs). This study provides insights into the comprehensive profile, horizontal gene transfer potential, hosts, and public health risks associated with antibiotic resistomes in river ecosystems exposed to chiral naproxen (NAP). Our findings demonstrate that NAP stress selectively enriches ARGs and mobile genetic elements (MGEs), thereby bolstering bacterial resistance to specific antibiotics. Importantly, the spatial variation of NAP chiral enantiomers influences the enantioselective response of bacterial communities to antibiotics. While (S)-NAP and (R)-NAP exhibit differing degrees of horizontal transfer potential, (S/R)-NAP notably facilitates microbial aggregation and DNA transport via type IV secretion system (T4SS)-related functional genes, promoting the conjugation of sul1. Moreover, (S/R)-NAP promotes the horizontal transfer of ARGs by stimulating ROS production and altering cell membrane permeability. Chiral NAP exposure induces pathogens to acquire ARGs and accelerates the proliferation of Burkholderia. ARG-Rank analysis indicates that the health risk posed by (R)-NAP exposure surpasses that of (S)-NAP, with the highest risk observed when both enantiomers are present. This study elucidates the horizontal transfer and transmission mechanisms of ARGs under chiral NAP stress, underscoring the potential health hazards associated with NAP chiral enantiomers.

2025-06-01·Separation and Purification Technology

Strong enhancement on diclofenac degradation in Cu(II)/H2O2 system by adding ascorbic acid: Efficiency, mechanism and influencing factors

作者: Zou, Jing ; Cai, Yajuan ; Wu, Jianying ; Chen, Lingxin ; Qiu, Shiyi ; Liu, Shupo ; Li, Fei ; Zhou, Zhenming ; Yang, Zhimin

Utilization of trace Cu(II) (at μM level) inherently existing in wastewater to activate hydrogen peroxide (H2O2) has exhibited significant potential to remove aqueous organic contaminants.Nevertheless, the Cu(II)/H2O2 system was only efficient under alk. conditions.Herein, ascorbic acid (H2A), an environmentally benign and natural reductant, was introduced to broaden pH range of Cu(II)/H2O2 process by expediting the Cu(II)/Cu(I) cycle.The H2A/Cu(II)/H2O2 system performed well in degrading diclofenac across a wide pH range from 4.0 to 9.0, and its kinetic rate constant of diclofenac elimination was 247 times greater than its counterpart without H2A at the optimal pH of 6.0, outperforming the performance of most previously reported reductant-enhanced Cu(II)/H2O2 system.ESR anal., periodate colorimetric method, and in situ Raman spectroscopy tests indicated that hydroxyl radical (HO.), rather than Cu(III), was the dominant reactive species of diclofenac degradationThirteen degradation products of diclofenac were identified by LC-Q-TOF-MS, and five different elimination pathways were proposed.Furthermore, the presence of SO2-4 exerted an insignificant influence on diclofenac degradation, while the addition of Cl-, HCO-3 and humic acid slightly suppressed the abatement of diclofenac.H2A/Cu(II)/H2O2 system was still highly efficient in degrading diclofenac in actual water matrix (i.e., reservoir water and lake water).Overall, this study provided an eco-friendly approach to enhance the oxidation capacity of the Cu(II)/H2O2 system over a wide pH range, which might be a potential technol. for degrading refractory organic pollutants in water treatment.

2025-06-01·Separation and Purification Technology

Peracetic acid activation by chitosan-derived nitrogen-doped carbon spheres loaded with zero-valent copper for efficient sulfamethazine degradation in groundwater

作者: Li, Long ; Xiao, Junyang ; Dong, Jie ; Deng, Junming ; Zhao, Mengxi ; Li, Xiting ; Li, Xing ; Dong, Haoran ; Yin, Wenjun ; Peng, Bo

Herein, chitosan-derived nitrogen-doped carbon spheres supported zero-valent copper (Cu@NCs) was prepared for the activation of peracetic acid (PAA) to degrade sulfamethazine (SMT) in groundwater under neutral condition.Several key influencing factors such as pyrolysis temperature, PAA concentration, Cu@NCs dosage, initial pH, inorganic ions and humic acid (HA) were investigated.The findings displayed that the Cu@NCs/PAA system could effectively degrade 94.5% SMT (10.0μM) in simulated groundwater in 30 min at low concentrations of PAA (50.0μM), and the optimum pH was 7.Radical quenching experiments and EPR examinations verified that radicals (^•OH, R-O^• and O•-2) and non-radical ¹O₂ were produced in the Cu@NCs/PAA system, with R-O^• and ¹O₂ being the primary contributors to the elimination of SMT.Zero-valent copper continuously transfers electrons through carbon spheres (electron shuttles) to produce Cu⁺, effectively activating the PAA to produce the active substance, accompanied by the production of Cu²⁺.Subsequently, Cu⁰ could convert the produced Cu²⁺ to Cu⁺ and then participate in the activation of the PAA.Direct electron transfer from SMT to PAA was enhanced by catalyst-mediated processes, which benefited from the function of carbon spheres in electron transport.Through cooperative efforts across radical and non-radical pathways, SMT was rapidly removed with trace amounts of PAA.In addition, inorganic ions (Cl^-, SO^2-₄, and HCO^-₃) had almost no effect on the Cu@NCs/PAA system, while HA had a certain degree of inhibition on the degradation of SMT.Furthermore, the Cu@NCs/PAA system displayed good reusability and easy recyclability.This work offered fresh perspectives and ideas on the removal of organic micropollutants using copper-based materials in the field of PAA-based AOPs, which promises to be an antibiotic-contaminated groundwater remediation solution

项与萘普生相关的新闻（医药）

2025-03-12

·PRNewswire

Psoriatic Arthritis Market Sees Major Shift with Growing Biosimilar Adoption | DelveInsight

The arrival of biosimilars like Celltrion's STEQEYMA and Biocon's YESINTEK is shaking up the psoriatic arthritis market, challenging blockbuster biologics with cost-effective alternatives. As competition intensifies, these biosimilars are reshaping treatment choices and driving a shift in the market landscape. LAS VEGAS, March 12, 2025 /PRNewswire/ -- Psoriatic arthritis (PsA) is a chronic inflammatory condition that affects approximately 112 per 100,000 adults worldwide. It is more prevalent in Europe and North America than in Asia and South America. In patients with psoriasis, the prevalence of psoriatic arthritis can range from 6% to 34% in Western populations. Despite its impact, many individuals with psoriatic arthritis remain undiagnosed or receive inadequate treatment, highlighting the need for increased awareness and access to specialized care. As per DelveInsight analysis, among the 7MM, the United States accounted for the highest number of prevalent cases of psoriatic arthritis in 2023, and these cases are expected to increase by the end of 2034 due to several key factors such as an increase in awareness and diagnosis, as well as the rapid prevalence of PsA. Psoriatic arthritis, occurring in approximately 20% of individuals with psoriasis, is a chronic inflammatory arthritis intricately linked to psoriatic arthritis. This aggressive condition is characterized by potential significant morbidity and compromised quality of life. Treatment approaches for psoriatic arthritis encompass a variety of strategies aimed at managing symptoms, slowing disease progression, and improving the overall quality of life. These approaches typically involve a combination of pharmacological therapies, lifestyle modifications, and, in severe cases, surgical interventions. Psoriatic arthritis treatment is highly individualized based on disease severity, response to therapy, and patient preferences, with multidisciplinary care from rheumatologists, dermatologists, and physical therapists playing a key role. Pharmacological treatment for psoriatic arthritis primarily targets inflammation and pain relief. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, are often the first line of defense, helping to reduce pain and inflammation. Disease-modifying antirheumatic drugs (DMARDs) like methotrexate, sulfasalazine, and leflunomide are commonly prescribed to prevent joint damage and suppress the inflammatory process. For individuals with mild-to-moderate psoriatic arthritis, oral small molecules (OSMs) like OTEZLA (apremilast) offer a convenient, non-injectable option by modulating inflammatory pathways. Biologic agents have revolutionized the treatment landscape for psoriatic arthritis. These medications specifically inhibit key molecules in the inflammatory cascade. TNF inhibitors like HUMIRA (adalimumab), ENBREL (etanercept), and REMICADE (infliximab) are frontline biologics that target tumor necrosis factor, a crucial driver of inflammation. Patients who do not respond to TNF inhibitors may benefit from IL-17 inhibitors like COSENTYX (secukinumab) and TALTZ (ixekizumab) or IL-12/23 inhibitors such as STELARA (ustekinumab). Learn more about the FDA-approved psoriatic arthritis drugs @ Drugs for Psoriatic Arthritis Treatment SKYRIZI (risankizumab), developed by AbbVie, is a humanized IgG1 monoclonal antibody that acts as an interleukin-23 (IL-23) antagonist. It can be used on its own or in conjunction with non-biologic DMARDs. In June 2022, the FDA approved SKYRIZI as the first and only targeted IL-23 inhibitor for adults with active psoriatic arthritis. Another biologic, TREMFYA (guselkumab by Janssen), was approved by the FDA in July 2020 as the first monoclonal antibody that selectively binds to the p19 subunit of IL-23, further expanding treatment options for psoriatic arthritis patients. BIMZELX (bimekizumab), developed by UCB Biopharma, is a humanized monoclonal antibody that targets IL-17A and IL-17F. It received European Commission approval in June 2023 for adults with active psoriatic arthritis and axial spondyloarthritis. On September 23, 2024, the FDA approved BIMZELX for treating adults with active psoriatic arthritis, non-radiographic axial spondyloarthritis (nr-axSpA) with objective inflammation, and active ankylosing spondylitis. In Phase III studies, BIMZELX showed meaningful responses in patients with inadequate TNF inhibitor responses and those new to biologics, indicating its potential as an important treatment option for psoriatic arthritis. In cases where joint damage becomes severe and unresponsive to medical therapies, surgical interventions like joint replacement surgery may be necessary to restore function and alleviate pain. Lifestyle changes, such as regular exercise, joint protection techniques, and weight management, are also critical in managing psoriatic arthritis, as excess weight can worsen symptoms and increase disease severity. The treatment landscape for psoriatic arthritis continues to evolve, offering hope to patients with more targeted therapies and improved outcomes. As companies like UCB Biopharma, AbbVie, and Janssen advance their biologic portfolios, the future looks promising for psoriatic arthritis management. The competition in the biosimilar market is intensifying as companies introduce cost-effective alternatives to blockbuster biologics. In December 2024, Celltrion announced FDA approval for STEQEYMA (ustekinumab-stba), a biosimilar to STELARA, for subcutaneous injection or intravenous infusion in adult and pediatric patients with plaque psoriasis and psoriatic arthritis, as well as adult patients with Crohn's disease and ulcerative colitis. Simultaneously, Biocon Biologics Ltd. is strengthening its position with positive Phase III results for YESINTEK, its biosimilar to ustekinumab, in adult patients with moderate to severe chronic plaque psoriasis. The pivotal randomized, double-blind, parallel-group study demonstrated comparable efficacy and safety to the reference biologic, STELARA, and the findings are being presented at the 2025 American Academy of Dermatology (AAD) Annual Meeting in Orlando, Florida. With the approval of STEQEYMA and the promising clinical outcomes for YESINTEK, these biosimilars are poised to challenge STELARA by offering cost-effective alternatives in key immunology indications. As pricing pressures and healthcare sustainability concerns drive the demand for biosimilars, these developments mark a significant shift in the treatment landscape, providing greater accessibility and affordability for patients while increasing competition in the immunology market. To know more about psoriatic arthritis treatment options, visit @ New Treatment for Psoriatic Arthritis The psoriatic arthritis market is buzzing with numerous companies advancing treatments to cater to the growing patient base. Several therapies are expected to enter the market during the forecast period, providing new hope for patients. Some of these potential therapies include ACELYRIN Inc.'s Izokibep, Novartis Pharmaceuticals' Secukinumab, UCB Biopharma SRL's Bimekizumab, and Bristol-Myers Squibb's Deucravacitinib. Additionally, AbbVie's Upadacitinib and Risankizumab, as well as Eli Lilly and Company's Ixekizumab, are also part of the promising pipeline. Other noteworthy therapies include Sun Pharma's ILUMYA/ILUMETRI, Bristol-Myers Squibb's SOTYKTU, and Affibody's Izokibep in collaboration with Acelyrin and Inmagene. With these advancements, the psoriatic arthritis treatment landscape is set for a major shift, offering patients more tailored and effective options. The companies involved in developing biosimilars include Alvotech, Teva, Biocon Biologics, Celltrion, Fresenius Kabi, and others. Discover which therapies are expected to grab major psoriatic arthritis market share @ Psoriatic Arthritis Market Report ILUMYA/ILUMETRI by Sun Pharma is an interleukin-23 (IL-23) inhibitor classified as a humanized, anti-IL-23p19 monoclonal antibody. It works by blocking inflammatory proteins (cytokines and chemokines) in the body. By inhibiting the effects of IL-23, ILUMYA helps control the release of other inflammatory proteins, including IL-17 and TNF-α. This mechanism reduces inflammation, decreases the number of inflammatory cells in psoriatic lesions, helps prevent plaque formation, and resolves tissue damage. The drug is currently undergoing evaluation in Phase III clinical development, actively recruiting subjects with active psoriatic arthritis who have prior exposure to anti-TNF agents, as well as those who are anti-TNF naïve. SOTYKTU, developed by Bristol-Myers Squibb, is the first and only novel oral selective tyrosine kinase 2 (TYK2) inhibitor being studied across multiple immune-mediated diseases. Deucravacitinib binds to the regulatory domain of the TYK2 enzyme, inhibiting its activation. This selective inhibition reduces the release of proinflammatory cytokines and chemokines, helping to control the inflammation associated with psoriatic arthritis and alleviating its signs and symptoms. Currently, the drug is being investigated for the treatment of psoriatic arthritis in a Phase III clinical trial. Izokibep, developed by Affibody in partnership with Acelyrin and Inmagene, is a unique antibody mimetic and a novel bispecific agent that potentially targets both subunits of the IL-17A homo-dimer and serum albumin. Affibody has entered into a partnership agreement with Acelyrin for the development and commercialization of izokibep and has completed a Phase II trial. As part of this agreement, Acelyrin obtained worldwide rights to izokibep, excluding selected Asian countries, where rights have been granted to Inmagene Biopharmaceuticals. In March 2024, Acelyrin announced the release of positive top-line results from the Phase IIb/III trial, indicating that izokibep was well-tolerated with a favorable safety profile. This drug is currently in Phase III clinical trial. Discover more about drugs for psoriatic arthritis in development @ Psoriatic Arthritis Clinical Trials The anticipated launch of these emerging therapies for psoriatic arthritis is poised to transform the market landscape in the coming years. As these cutting-edge treatments continue to mature and gain regulatory approval, they are expected to reshape the psoriatic arthritis market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the psoriatic arthritis market size was USD 9 billion in 2021 and is expected to grow significantly in the coming years. This growth can be attributed to the introduction of upcoming therapies and the rising prevalence of the condition. The anticipated launch of these therapies is also expected to attract new entrants to the psoriatic arthritis market, resulting in increased competition and innovation. DelveInsight's latest published market report titled " Psoriatic Arthritis Market Insight, Epidemiology, and Market Forecast – 2034" will help you discover which market leader is set to capture the largest market share. The report provides comprehensive insights into country-specific treatment guidelines, patient pool analysis, and epidemiology forecasts to help understand key opportunities and assess the market's underlying potential. The psoriatic arthritis market report offers epidemiological analysis for the study period 2020–2034 in the 7MM, segmented into: Total Prevalent Cases of Psoriatic Arthritis Total Diagnosed Prevalent Cases of Psoriatic Arthritis Gender-specific Diagnosed Prevalent Cases of Psoriatic Arthritis Severity-specific Diagnosed Prevalent Cases of Psoriatic Arthritis The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM Psoriatic Arthritis market. Highlights include: 10-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this psoriatic arthritis market report to assess the epidemiology forecasts, understand patient journeys, gain insights into KOLs' opinions about upcoming treatment paradigms, and identify the factors contributing to changes in the psoriatic arthritis market. Additionally, stay informed about the mitigating factors that can enhance your market position in the psoriatic arthritis therapeutic space. Related Reports Psoriatic Arthritis Pipeline Psoriatic Arthritis Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key schizophrenia companies, including Affibody, Kymera, Selection Therapeutics GmbH, Jiangsu HengRui Medicine Co., Ltd., Nimbus Lakshmi, Inc., Hansoh BioMedical R&D Company, Bio-Thera Solutions, ACELYRIN Inc., among others. Psoriatic Arthritis Epidemiology Forecast Psoriatic Arthritis Epidemiology Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and Psoriatic Arthritis epidemiology trends. Ankylosing Spondylitis Market Ankylosing Spondylitis Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key Ankylosing Spondylitis companies, including UCB, AbbVie, Pfizer, Astella, Amgen, Janssen Biotech, Pozen, Novartis, Iroko Pharmaceuticals, Syntex Pharmaceuticals, Horizon Pharma, Eli Lilly and Company, among others. Psoriasis Market Psoriasis Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key Psoriasis companies, including Amgen, Janssen, Abbvie, Novartis, AstraZeneca, Bausch Health, Eli Lilly, Sun Pharmaceutical, Janssen Biotech, UCB Inc., LEO Pharma, Promius Pharma, Mayne Pharma, Bausch Health Companies, MC2 Therapeutics, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期上市批准临床结果临床2期

2025-03-09

·药事纵横

不可忽视的创新药理化性质之溶解度

只有溶解状态的药物才能发挥生物学作用，溶解度是影响药物生物利用度的重要因素之一。对创新药而言，无论是发现阶段还是开发阶段，对溶解度的研究都是至关重要的工作。一、溶解度定义溶解度是指在一定条件下，化合物在溶剂介质中达饱和时所能达到的最高浓度，溶解度不是化合物固有属性，取决于诸多因素，如化合物结构（可电离基团、亲脂性基团、氢键）、溶液中引入化合物的物理状态（固态、液态）、溶剂的组成和物理状态（溶剂种类、助溶剂及含量、溶液成分、酸碱度、温度）、测定方法（平衡时间、分离技术、检测手段）等。二、创新药对溶解度的阶段性考量创新药研发可笼统分为发现阶段和开发阶段（临床前研究、临床研究）。在发现阶段我们致力于将化合物溶解成溶液来进行生物测定和初步概念验证，因此多采用万能溶剂DMSO提高化合物溶解度，这一阶段的工作与动力学溶解度高度相关。而在开发阶段，主要目的是筛选合适的剂型以及完成注册申报所要求完成的详细技术研究，此时继续使用DMSO作为溶剂既有可能误导产生错误的结论。加上此时药物晶型已基本确定，采用热力学溶解度来表征溶解度对制剂开发具有很好的指导作用。热力学溶解度：也称平衡溶解度，是向晶态化合物中直接加入水系溶剂，经过长时间混合后使已溶解物质和固态物质达到平衡状态。热力学溶解度常用于指导制剂开发和制定开发策略、诊断体内结果同时也是申报资料的重要文件组成。动力学溶解度：将化合物溶解于有机良溶剂中（通常为DMSO），然后被缓缓加入水系溶剂介质中。动力学溶解度常被用于开发用于动物给药的通用制剂、建立化合物结构-溶解度关系、警示存在的吸收或生物测定易变性、诊断错误的生物测定结果。过饱和稳定性提到动力学溶解度和热力学溶解度，这里还有一个跟两者都相关的概念，即过饱和稳定性。假设我们获得了一个活性或安全性都非常具有吸引力的化合物，但溶解度很低，且低溶解度与其他构效关系相关联（不易通过结构优化解决溶解度问题），此时是否只有放弃继续开发一条路可以走呢？答案是否定的。此时，可以将低热力学溶解度化合物分为具有低过饱和稳定性和高过饱和稳定性两类，对于高过饱和稳定性化合物（尤其是体内实现过饱和）具有较好的发展前景。人体的胃肠道是易发生过饱和现象的场所，例如碱性化合物在胃液中溶解良好，当来到小肠时因pH改变溶解度降低，有析出的风险，但化合物如具有较高够饱和倾向可减少或避免析出，提高生物利用度。在体外研究中，通常采用FaSSIF介质模拟胃肠道来进行体内过饱和稳定性的测定，如果一种化合物在FaSSIF中没有表现出可接受的热力学溶解度或过饱和稳定性，它可能代表最坏的情况，并标志较高的开发风险。三、溶解度接受标准在创新药研发中我们常常会面临这样的问题，化合物所需的最低溶解度是多少？这个问题没有绝对的答案。发现阶段溶解度的评价目的是指导化合物选择与推进。此阶段对于最低溶解度需求，William Curatolo等人提出了最大剂量理论，即MAD与溶解性和渗透性之间的关系。MAD=S*Ka*SIWV.SITT，其中S为溶解度（mg/mL，pH6.5），Ka为渗透率（min-1），SIWV为小肠水容量（约为250 mL），SITT为小肠经过时间（约为270min）。化合物剂量越低，渗透性越好，达人体最大吸收时所需的溶解度越低，反之亦然。例如有三个候选化合物A、B、C，其拟定计量、渗透率均已知，计算出各自所需的最低溶解度，结果见下表。表1在给定剂量和渗透率下，达目标吸收所需的最低可接受溶解度可以看出化合物A和B具有相同的最大吸收剂量，化合物A的渗透率是B的十倍，计算所得化合物A的最低可接受溶解度是B的十分之一；化合物A与化合物C具有相同渗透率，但化合物C的最大吸收剂量是A的十倍，计算所得化合物C的最低可接受溶解度是A的十倍；化合物C最大吸收剂量是B的十倍，化合物C的渗透率也是B的十倍，经计算化合物C的最低可接受溶解度与B相同。同样基于MAD理论，Lipinski依据经验对剂量和渗透率的低、中、高水平赋予确定的数值，剂量低中高水平分别为0.1 mg/mL、1 mg/mL和10 mg/mL，渗透率的低中高水平分别为0.005 min-1、0.02 min-1和0.1min-1，并依据此经验数据将溶解度与剂量和渗透性之间的关系用图形更直观的表示出来。图1最低可接受溶解度示意图（图片来源于文献4）由上图可知，如果化合物渗透性足够好，最大吸收剂量最够低（效价足够高），那么即便化合物溶解度仅有1 μg/mL也是可以不借助药剂学手段或结构修饰就能进一步开发的。开发阶段进入开发阶段常被用于回答最低可接受溶解度问题就是大名鼎鼎的BCS生物学分类系统，该系统按照溶解性和渗透性将化合物分为4类。 I类：高溶高渗，是理想的口服吸收药物，多为两亲性化合物，如阿巴卡韦、对乙酰氨基酚、阿米洛利、阿托品、美托洛尔、依那普利、地尔硫卓、去甲替林等，体内吸收的限制因素为溶出度。 II类：低溶高渗，多为亲脂性化合物，如胺碘酮、阿托伐他汀、阿奇霉素、环丙沙星、苯妥英、萘普生、双氯芬酸、地高辛、双氯芬酸、吡罗昔康等，体内吸收量的限制因素是溶解度，可通过制剂学手段来提高该类化合物的溶解度。 III类，高溶低渗，多为亲水性化合物，如阿昔洛韦、西咪替丁、阿莫西林、阿替洛尔、二膦酸盐、红霉素、雷尼替丁、头孢唑啉等，吸收速率的限制因素是渗透性，可通过前药技术提高渗透性。 IV类，低溶低渗，通常无法预期体内体外相关性，开发此类化合物风险较大，如两性霉素、紫杉酚、特非那定、新霉素、甲氨蝶呤、环丙沙星、呋塞米、氢氯噻嗪等。基于文献数据的BCS分类体统溶解性可用D0（既定计量下250 mL中药物浓度与药物在水中饱和溶解度之比）评价，D0≤1为高溶解性，D0＞1为低溶解性；渗透性可粗略用亲脂性指标logP来评价，以美托洛尔（logP1.72）为标杆，logP大于美托洛尔的定义为高渗透性，logP低于美托洛尔的定义为低渗透性。当然，如果药物肠道吸收是载体介导的，光凭亲脂性评价渗透性会有较大偏差。四、溶解度的影响因素影响溶解度的因素的包括结构特征和生理环境。结构特征包括亲脂性、分子大小、解离常数和晶格能等，生理环境包括胃肠道生理环境、种属差异和食物的影响。五、提升溶解度的手段当候选化合物溶解度不理想时，研发团队必将致力于提升溶解度，优化手段包括结构修饰、制剂策略等，但首选结构修饰，将问题解决节点前置，避免将过多难题留给制剂团队。常见的结构修饰手段见下图。六、结论新药开发面临着多重挑战。有人形容新药发现过程就像玩杂耍，为达到成功需要同时监控不同参数的组合并维持平衡。溶解度就是其中一个重要参数。然而溶解度并不是孤立的数值，会受到物理环境和生理环境等多种因素影响。对溶解度研究的同时也应关注溶解度与其他因素的相互影响，进行多参数优化。虽然不能保证候选化合物一定在临床中成功，但它可以增加开发过程成功的机率。参考文献 [1]Cunliang Zhang，Equilibrium solubility, Hansen solubility parameter, dissolution thermodynamics, transfer property and preferential solvation of zonisamide in aqueous binary mixtures of ethanol, acetonitrile, isopropanol and N,N-dimethylformamide，Journal of Molecular Liquids 326 (2021) 115219. [2] Suzanne M. Skolnik, Automated supersaturation stability assay to differentiate poorly soluble compounds in drug discovery, Journal of Pharmaceutical Sciences, Volume 107, Issue 1, January 2018, Pages 84-93 [3] Srini Venkatesh, Role of the Development Scientist in Compound Lead Selection and Optimization, JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 89, NO. 2, FEBRUARY 2000,145-154. [4] Christopher A. Lipinski, Drug-like properties and the causes of poor solubility and poor permeability, Journal of Pharmacological and Toxicological Methods 44 (2000) 235- 249. [5]William Curatolo,Physical chemical properties of oral drug candidates in the discovery and exploratory developmentsettings,research focus,PSTT Voll 1(9) ,1998,387-393. [6]Kevin C .Johnson,Guidance in the Setting of Drug Particle Size Specifications to Minimize Variability in Absorption,Pharmaceutical Research,13(12),1996,1795-1798. [7] Arik Dahan, Prediction of Solubility and Permeability Class Membership: Provisional BCS Classification of the World’s Top Oral Drugs, The AAPS Journal, Vol. 11, No. 4, December 2009,740-746. [8]类药性质：概念、结构设计与方法：从ADME到安全性优化 [9]Ramu Samineni,Emerging Role of Biopharmaceutical Classification and Biopharmaceutical Drug Disposition System in Dosage form Development: A Systematic Review,Turk J Pharm Sci 2022;19(6):706-713 药事纵横投稿须知：稿费已上调，欢迎投稿

诊断试剂

2025-03-04

·FiercePharma

Glenmark issues another recall, this time for nearly 1.5M bottles of generic ADHD drug

Glenmark Pharma is recalling nearly 1.5 million bottles of the attention-deficit/hyperactivity disorder drug atomoxetin. Glenmark Pharma, an India-based drug manufacturer that has been the focal point of a spate of recalls in recent years, has issued another. This time, the product pull covers about 1.48 million bottles of the generic attention-deficit/hyperactivity disorder (ADHD) drug atomoxetine.Eli Lilly previously sold the branded version of the drug, Strattera, but discontinued all strengths in 2023 after the arrival of generics.Unlike stimulant-based drugs that make up the bulk of ADHD treatment, including those like Vyvanse and Adderall, atomoxetine is a selective norepinephrine reuptake inhibitor (sNRI).The recall was triggered by the presence of unacceptable levels of N-nitroso atomoxetine, a possible carcinogen, in multiple Glenmark atomoxetine batches, according to the FDA. The voluntary pull, which began Jan. 29, covers bottles of the drug in strengths ranging from 10 mg to 100 mg, the FDA said on its Enforcement Report webpage. The ADHD drugs were manufactured in Glenmark’s facility in Goa, India, and were distributed nationwide. Glenmark has weathered a string of recalls in recent years due to both manufacturing and labelling issues.In June 2024, the company recalled 114 batches of 750 mg potassium chloride extended-release capsules—or roughly 47 million capsules—over concerns that they failed to dissolve properly.In December, the company recalled 90,528 bottles of the high blood pressure drug diltiazem hydrochloride in tablet and extended-release forms due to unacceptable levels of another N-nitroso compound, N-nitroso-Desmethyl-Diltiazem.In separate actions in 2023, Glemark recalled 1,200 bottles of trandolapril and verapamil hydrochloride extended-release tablets used to treat high blood pressure; 37,200 bottles of Indomethacin, which is a non-steroidal anti-inflammatory used to treat pain and arthritis symptoms; and five lots (no bottle count provided) of Naproxen that is used to reduce fever or relieve mild pain.The previous year it recalled 98,307 packs of mometasone furoate topical solution, a corticosteroid lotion that treats skin conditions such as eczema, psoriasis, allergies and rash.

临床结果

100 项与萘普生相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00118	萘普生	G02CC02 M01AE02 M02AA12	DB00788

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
疼痛	中国	华中药业股份有限公司	1983-01-01
痛风	中国	华中药业股份有限公司	1982-01-01
镇痛	日本	Nipro ES Pharma KK	1978-01-24
炎症	日本	Nipro ES Pharma KK	1978-01-24
强直性脊柱炎	美国	Atnahs Pharma US Ltd.	1976-03-11
幼年特发性关节炎	美国	Atnahs Pharma US Ltd.	1976-03-11
骨关节炎	美国	Atnahs Pharma US Ltd.	1976-03-11
类风湿关节炎	美国	Atnahs Pharma US Ltd.	1976-03-11

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
消化性溃疡	临床2期	英国	Oxford Pharmascience Ltd.	2015-05-01
疼痛	临床2期	英国	Oxford Pharmascience Ltd.	2015-02-01
风湿性疾病	临床2期	英国	Oxford Pharmascience Ltd.	2015-02-01
牙痛	临床2期	美国	Iroko Pharmaceuticals LLC	2010-10-01
腰痛	临床2期	-	Targeted Medical Pharma, Inc.	2009-02-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03771612 (CTgov)	早期临床1期	炎症	144	Naproxen (Naproxen)	鹹廠醖膚獵夢積糧鏇餘(夢襯繭網衊衊遞鬱憲廠) = 窪膚衊齋蓋憲窪醖構範鹹鹹淵膚鹹齋製夢構繭 (蓋廠觸夢遞製觸窪糧艱, 鏇獵構遞繭鏇簾網獵蓋 ~ 鬱積蓋積醖憲遞窪餘窪) 更多	-	2025-02-25
				Placebos (Placebo)	鹹廠醖膚獵夢積糧鏇餘(夢襯繭網衊衊遞鬱憲廠) = 構衊簾憲製願鹹壓觸艱鹹鹹淵膚鹹齋製夢構繭 (蓋廠觸夢遞製觸窪糧艱, 製壓襯願蓋顧糧觸壓獵 ~ 選鏇衊顧觸願壓範壓蓋) 更多
NCT05026320 (CTgov)	临床2期	挫伤 \| 软组织损伤	76	Placebo gel	願製醖獵鏇簾範夢範憲(製築衊醖夢襯遞廠構繭) = 醖壓壓壓構鬱簾鑰遞糧願簾觸觸糧鑰壓範齋顧 (獵齋選網鹽憲繭構鬱觸, 壓選構齋獵積繭網窪壓 ~ 憲獵鬱齋願鑰淵憲艱蓋) 更多	-	2025-01-22
EULAR2024	N/A	膝关节滑膜炎 \| 膝关节炎	145	Naproxen + Acetaminophen	餘網鹹醖壓選繭餘範憲(齋簾壓範鹹鏇網簾餘製) = 選壓鹽製鹹顧齋鏇顧憲鹽築蓋簾顧窪鬱獵範夢 (製獵淵壓鏇選醖範製襯 )	积极	2024-06-05
				Naproxen + Acetaminophen + Methotrexate 10mg per week + Folic acid 10mg per week	餘網鹹醖壓選繭餘範憲(齋簾壓範鹹鏇網簾餘製) = 構網壓醖觸鹹範鑰糧齋鹽築蓋簾顧窪鬱獵範夢 (製獵淵壓鏇選醖範製襯 )
NCT03347929 (Pubmed \| Pain) 人工标引	临床4期	坐骨神经痛	123	Naproxen 500 mg	築壓齋簾蓋壓觸鏇齋鬱(齋糧夢壓網積艱憲襯衊) = 蓋鑰襯窪顧齋襯鏇範夢構窪範範鬱襯壓鏇壓鬱 (膚餘廠鏇襯糧艱蓋積鬱 ) 更多	不佳	2024-06-04
				Placebo	-
NCT04694300 (CTgov)	临床4期	口颌疾病 \| 急性疼痛	30	Tramadol+Naproxen (Naproxen Sodium)	憲壓醖製獵製糧糧醖襯(窪夢鏇廠鬱構鬱齋鏇獵) = 齋衊繭鹹鹽醖窪網構廠淵艱簾簾構鹹獵網窪廠 (製鹹簾蓋繭糧顧廠網觸, 繭網構糧鑰築構衊襯製 ~ 網願鹹夢選積廠範觸艱) 更多	-	2024-05-16
				Tramadol+Acetaminophen (Acetaminophen)	憲壓醖製獵製糧糧醖襯(窪夢鏇廠鬱構鬱齋鏇獵) = 餘構齋廠衊遞襯艱醖齋淵艱簾簾構鹹獵網窪廠 (製鹹簾蓋繭糧顧廠網觸, 鑰構觸鏇鑰鑰淵憲遞獵 ~ 願顧遞窪繭齋齋範衊醖) 更多
NCT02502006 (CTgov)	临床1期	-	16	Celecoxib (Celecoxib)	遞醖窪糧網獵廠鏇鹽襯(鑰窪淵夢淵餘醖繭鹽簾) = 鹽積網餘糧壓廠願窪衊網顧鏇鑰遞鏇蓋範糧夢 (觸壓簾鹽艱鏇選鬱網膚, 鹹膚蓋選簾網餘鹹繭鏇 ~ 鏇糧齋積廠鬱蓋範憲衊) 更多	-	2023-12-13
				Naproxen (Naproxen)	遞醖窪糧網獵廠鏇鹽襯(鑰窪淵夢淵餘醖繭鹽簾) = 齋醖構襯膚艱獵簾選構網顧鏇鑰遞鏇蓋範糧夢 (觸壓簾鹽艱鏇選鬱網膚, 製鹹鏇憲願獵繭鹽淵糧 ~ 築鬱觸遞顧簾襯憲醖齋) 更多
NCT03697720 (CTgov)	临床4期	痛经 \| 膀胱痛	26	Naproxen	繭鬱醖選網衊構範衊壓(範廠選鑰繭醖醖膚顧鑰) = 窪觸選壓鬱餘襯繭觸餘壓鹽簾膚鑰繭願築壓鹹 (鹽衊蓋廠積齋鹽遞壓製, 顧衊齋鹽餘鹽鹽餘顧遞 ~ 鬱顧鏇夢餘鏇繭繭艱鹹) 更多	-	2023-10-18
NCT00346216 (PRECISION, Pubmed \| Eur Heart J Cardiovasc Pharmacother)	临床4期	关节炎	24,081	Celecoxib	糧獵遞膚糧餘繭淵艱鏇(簾遞窪夢齋衊糧壓襯遞) = 艱範遞鑰觸顧膚構製遞窪範鬱鏇夢齋積觸糧壓 (鑰壓襯鏇獵選範遞淵醖 )	积极	2022-03-02
				Ibuprofen	糧獵遞膚糧餘繭淵艱鏇(簾遞窪夢齋衊糧壓襯遞) = 觸壓醖網繭蓋築構廠顧窪範鬱鏇夢齋積觸糧壓 (鑰壓襯鏇獵選範遞淵醖 )
NCT00826462 (CTgov)	临床4期	网球肘	177	Naprosyn (Control Group: Wait-and-see Treatment)	餘積膚積廠膚鏇範積鹽(襯糧憲憲廠壓製觸網願) = 構鬱築製製遞齋齋製艱糧願艱齋蓋積網構憲窪 (遞願製遞鬱鹽衊夢築膚, 齋網網齋衊鹹鏇繭鹹築 ~ 壓觸鏇鏇觸衊餘願膚網) 更多	-	2022-01-24
				Placebo (Placebo Injection in Combination With Physical Therapy)	餘積膚積廠膚鏇範積鹽(襯糧憲憲廠壓製觸網願) = 積願築願獵觸鏇壓網淵糧願艱齋蓋積網構憲窪 (遞願製遞鬱鹽衊夢築膚, 醖鬱簾簾繭醖遞醖壓繭 ~ 糧獵鹽憲選糧願網積淵) 更多
NCT03654326 (7264-034 \| MK-7264-034, CTgov)	临床2期	疼痛	187	Placebo+Naproxen+Gefapixant (Gefapixant)	觸艱廠範構蓋網廠夢衊(壓鬱遞鏇膚憲顧鹽繭網) = 網製築獵齋獵窪鏇鹹獵遞蓋獵糧遞顧構鏇餘餘 (鏇餘築範膚鏇糧網糧衊, 繭壓鬱襯願築艱積糧鬱 ~ 醖構夢齋構鑰願憲糧鹹) 更多	-	2021-07-07
				Placebo+Naproxen (Placebo)	觸艱廠範構蓋網廠夢衊(壓鬱遞鏇膚憲顧鹽繭網) = 簾鬱餘鑰衊顧憲鹹糧醖遞蓋獵糧遞顧構鏇餘餘 (鏇餘築範膚鏇糧網糧衊, 壓觸鏇網糧鹽構鏇壓膚 ~ 獵糧範艱觸膚鑰鏇齋憲) 更多