A Phase 1, Fixed Sequence, Open-Label Study to Evaluate the Effect of Multiple Doses of Rabeprazole on the Pharmacokinetics of a Single Dose of Radiprodil in Healthy Adult Participants

开始日期2024-08-26

申办/合作机构

GRIN Therapeutics, Inc.

[+1]

100 项与雷贝拉唑钠/甲硝唑/阿莫西林相关的临床结果

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100 项与雷贝拉唑钠/甲硝唑/阿莫西林相关的转化医学

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100 项与雷贝拉唑钠/甲硝唑/阿莫西林相关的专利（医药）

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1,352

项与雷贝拉唑钠/甲硝唑/阿莫西林相关的文献（医药）

2025-05-01·Current drug discovery technologies

Delineating CYP2C19-mediated Interactions: Network Pharmacology Investigation of Ilaprazole and Clopidogrel versus Conventional Proton Pump Inhibitors

Article

作者: Narayanasamy, Damodharan ; Ananthathandavan, Priyadharshini

Background::

Clopidogrel, an antiplatelet drug commonly used in cardiovascular disease, is metabolized by the liver mainly through CYP2C19. Concomitant use of Proton pump inhibitors along with clopidogrel may affect the potency of clopidogrel by CYP2C19 inhibition. However, a novel PPI, ilaprazole is known to differ in its pharmacokinetic features, given the potential differences between ilaprazole’s interactions and their metabolism with clopidogrel. Network pharmacology investigation could be a useful tool to evaluate the drug-drug interaction between them.

Methodology::

The molecular structures and targets were retrieved from PubChem and SwissTargetPrediction to establish the information related to the identified drugs. The possible shared targets between the clopidogrel and PPIs were explored by a Venn analysis. Subsequently, Protein-Protein Interaction networks were established using the STRING database. Hub genes were also determined using the Cytoscape cytoHubba plugin.

Results & Discussion::

Ilaprazole (13.6%) and pantoprazole (13.6%) were characterized by fewer targets being shared with clopidogrel compared to conventional PPIs (14.9%). Moreover, CYP2C19 was not a hub gene in ilaprazole and pantoprazole interactions, which indicated no significant CYP2C19 involvement. On the other hand, CYP2C19 functioned as a hub gene in the interactions with rabeprazole, lansoprazole, dexlansoprazole, omeprazole, and esomeprazole. As a result, patients receiving pantoprazole and ilaprazole would be at a lower risk for developing adverse cardiovascular events by maintaining the clopidogrel therapeutic effect.

Conclusion::

The application of the network pharmacology technique allows us to consider the potential for different effects of PPIs on clopidogrel and its metabolism via CYP2C19. There is a lower chance of experiencing adverse effects from an interaction between ilaprazole and clopidogrel as ilaprazole has not been linked to CYP2C19. More research is necessary to confirm these results and provide clinical guidance for patients undergoing clopidogrel and PPI combination therapy.

2025-04-02·JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY

Vonoprazan improves the efficacy of bismuth quadruple therapy containing doxycycline and metronidazole as first-line Helicobacter pylori treatment in penicillin-allergic patients: a randomized controlled trial

Article

作者: Chen, Ye ; Li, Lan ; Ma, Dan ; Sun, Kefang ; Zhu, Renke ; Wang, Jiewei ; Yan, Tianlian ; Gao, Jianguo ; Gu, Qing ; Wang, Jinghua

Abstract:

Background:

Helicobacter pylori eradication in penicillin-allergic patients presents challenges. Options of effective regimens are lacking in areas where tetracycline is unavailable.

Objectives:

To evaluate the efficacy of replacing the proton pump inhibitor (PPI) with a potassium-competitive acid blocker (P-CAB, vonoprazan) in standard bismuth quadruple therapy containing doxycycline and metronidazole as a first-line treatment for H. pylori.

Methods:

This prospective randomized clinical trial enrolled 332 naive patients with H. pylori infection and penicillin allergy. Participants were randomly assigned in a 1:1 ratio to either the 14 day P-CAB/BDM group (vonoprazan 20 mg twice daily, colloidal bismuth 200 mg twice daily, doxycycline 100 mg twice daily and metronidazole 400 mg three times daily) or the 14 day PPI/BDM group (rabeprazole 10 mg twice daily, and the same dose of the three other drugs as in the 14 day P-CAB/BDM group).

Results:

Eradication rates in the P-CAB/BDM and PPI/BDM groups were 90.4% and 71.1% (P value for superiority was 0.013), respectively, by ITT analysis. The efficacy of P-CAB/BDM remained non-inferior and even superior to PPI/BDM therapy in all ITT, modified ITT and PP analyses. The overall frequency of adverse events (39.8% and 40.4%; P = 0.911) and compliance (88.0% and 91.0%; P = 0.372) were similar between P-CAB and PPI regimens. Patients with higher body surface area were significantly associated with eradication failure in both groups (P < 0.05).

Conclusions:

The 14 day P-CAB/BDM therapy provided a satisfactory eradication rate of >90% (ITT analysis) and had a good safety profile as first-line H. pylori therapy, providing an alternative option for penicillin-allergic patients.

2025-04-01·JOURNAL OF CLINICAL PHARMACOLOGY

Relative Bioavailability of Dordaviprone (ONC201) is Not Affected by Co‐Administration of the Proton‐Pump Inhibitor Rabeprazole

Article

作者: Mullin, Mark J. ; Morrison, Marion ; Faison, Shamia L. ; Batonga, Joelle ; Naderer, Odin ; Bartkus, Angela ; Arumugham, Thangam ; Tippin, Tim

Abstract:

Dordaviprone (ONC201) is a novel, orally administered, anti‐cancer, small molecule imipridone with demonstrated antitumor effects in patients with glioma. Dordaviprone in vitro solubility is significantly reduced at pH >4.5. Concomitant use of acid reducing agents (ARAs) may therefore impact dordaviprone solubility and bioavailability. This open‐label, single‐sequence, three‐period crossover study evaluated the effect of proton‐pump inhibitor rabeprazole on dordaviprone pharmacokinetics (PK). Periods were consecutive and comprised of period 1 (days 1‐3), period 2 (days 4‐9), and period 3 (days 10‐13). In period 1, participants received a single oral 625 mg dose of dordaviprone on day 1. In period 2, participants received six consecutive days of QD 20 mg rabeprazole alone. In period 3, patients received one oral dose of 20 mg rabeprazole (the seventh consecutive daily dose), followed 2 h later by a single 625 mg dordaviprone oral dose. PK blood samples were collected and analyzed from pre‐dose 72 h following dordaviprone administration in periods 1 and 3. Dordaviprone exposure PK parameters were similar following administration of dordaviprone alone or with rabeprazole. Geometric mean ratios and 90% CIs for dordaviprone exposure parameters with and without rabeprazole following dordaviprone administration fell within bioequivalence limits of 80.00%‐125.00% for Cmax (97.19% [86.43‐109.28]), AUClast (102.21% [95.19‐109.75]), and AUCinf (102.27% [95.21‐109.86]), indicating no effect of multiple oral doses of rabeprazole on dordaviprone relative bioavailability. Six of the 16 participants reported treatment‐emergent adverse events (TEAEs); dordaviprone‐related TEAEs were reported by three participants and were limited to mild nausea and dizziness. No dordaviprone dose adjustment or ARA treatment modification is warranted.

项与雷贝拉唑钠/甲硝唑/阿莫西林相关的新闻（医药）

2023-12-19

·PRNewswire

Proton Pump Inhibitors (PPIs) Market to grow by USD 807.89 million from 2023-2028 | North America to account for 36% of market growth - Technavio

NEW YORK, Dec. 19, 2023 /PRNewswire/ -- The proton pump inhibitors (PPIs) market size is expected to grow by USD 807.89 million from 2023 to 2028. In addition, the momentum of the market will progress at a CAGR of 4.86% during the forecast period, according to Technavio Research. The market is categorized by Product (OTC PPIs and Prescription PPIs), Route Of Administration (Oral and Injectable), and Geography (North America, Europe, Asia, and Rest of World (ROW)). North America will contribute 36% to the growth of the global market during the forecast period. Factors such as the presence of large pharmaceutical companies that offer both branded and generic PPIs and the presence of a proper regulatory framework for the approval of new drugs in the region drive regional market growth. This report offers an up-to-date analysis of the current market scenario, the latest trends and drivers, and the overall market environment. Read a FREE PDF Sample Report Continue Reading Technavio has announced its latest market research report titled Global Proton Pump Inhibitors (PPIs) Market 2024-2028 Company Profile: Amgen Inc., AstraZeneca Plc, Aurobindo Pharma Ltd., Bausch Health Companies Inc., Bayer AG, Cipla Ltd., Dr Reddys Laboratories Ltd., Eisai Co. Ltd., Eli Lilly and Co., Glenmark Pharmaceuticals Ltd., Johnson and Johnson, Perrigo Co. Plc, Pfizer Inc., RedHill Biopharma Ltd., Sanofi, Sun Pharmaceutical Industries Ltd., Takeda Pharmaceutical Co. Ltd., Teva Pharmaceutical Industries Ltd., The Procter and Gamble Co., Zydus Lifesciences Ltd. Amgen Inc. - The company offers proton pump inhibitors such as LUMAKRAS with gastric acid-reducing agents and decreased sotorasib concentrations. To gain access to more vendor profiles available with Technavio, buy the report! Proton Pump Inhibitors (PPIs) Market: Health Analysis Proton Pump Inhibitors (PPIs) play a significant role in managing various gastrointestinal conditions, including Gastroesophageal Reflux Disease (GERD), Peptic Ulcer Disease, and Gastritis, effectively suppressing acid production. Helicobacter pylori, a common bacterium, often contributes to Peptic Ulcer Disease, for which both prescription and non-prescription PPIs are used as part of the treatment regimen, ensuring comprehensive therapy against this bacterial infection. The Proton Pump Inhibitor Market showcases a diverse range of medications, including FDA-approved and generic PPIs, aiming to alleviate symptoms associated with acid-related disorders like Heartburn, Erosive Esophagitis, and NSAID-Induced Ulcers. Understanding the potential side effects of Proton Pump Inhibitors is crucial, as they are associated with complications such as Duodenal Ulcers, necessitating careful consideration of their usage and monitoring for optimal gastrointestinal health. Heartburn, often associated with Acid-related Disorders, manifests as a burning sensation in the chest due to stomach acid reflux into the esophagus. This common symptom occurs post-meals, triggered by specific foods or lying down, contributing significantly to Acid-related Disorders' discomfort. Managing heartburn involves dietary modifications, maintaining an upright posture after eating, and utilizing medications to mitigate stomach acid production. Chronic heartburn, if left unaddressed, may lead to erosive esophagitis or Barrett's esophagus, highlighting its role within Acid-related Disorders and emphasizing the need for prompt intervention to alleviate symptoms and prevent complications. Proton Pump Inhibitors (PPIs) Market: Segmentation Analysis The OTC PPIs segment will be significant during the forecast period. The products in this segment are defined as medicines that are sold directly to patients or consumers without a prescription from a healthcare professional. Furthermore, the availability of OTC PPIs provides patients with an option for self-medication and reduces the financial burden associated with medication treatment. Learn about the contribution of each segment summarized in concise infographics and thorough descriptions. View a PDF Sample Report These six medications—Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole, Rabeprazole, and Dexlansoprazole—belong to the class of proton pump inhibitors, commonly prescribed to treat various gastrointestinal conditions by reducing stomach acid production. Each drug within this group exhibits distinct pharmacokinetic properties and efficacy profiles, catering to individual patient needs for managing acid-related disorders. "Besides analyzing the current market scenario, our report examines historic data from 2017 to 2021"- Technavio Proton Pump Inhibitors (PPIs) Market: Driver & Trend: Driver Reformulation of drugs Growth in prescription rate Strong prevalence of gastroesophageal reflux disease Reformulation of drugs drives market growth. It provides an opportunity to grab patent term extensions, which can delay the entry of generic versions into the market. The availability of two dosage forms, NEXIUM 10 mg and 20 mg, will increase the consumption of the drug for various indications, particularly acid-related diseases, in both children aged one year and above the older patients with difficulty in swallowing. The rising prevalence of obesity is a leading market trend. Identify key trends, drivers, and challenges in the market. Download a sample report to gain access to this information. Unraveling Therapeutic Efficacy and Potential Complications in Gastrointestinal Health The Proton Pump Inhibitors (PPIs) Market comprises an extensive range of medications tailored to manage diverse acid-related disorders like Gastroesophageal Reflux Disease (GERD), Peptic Ulcer Disease, and Gastritis. FDA-approved prescription PPIs play a significant role in treating conditions such as Zollinger-Ellison Syndrome and NSAID-Induced Ulcers, contributing significantly to gastrointestinal health and acid suppression. It's essential to recognize that both non-prescription and generic PPIs exist within this market, each exhibiting distinct efficacy profiles and potential side effects, including complications associated with prolonged use such as erosive esophagitis. Understanding the complexities of these medications is crucial for addressing various conditions and ensuring patient well-being amid the dynamic landscape of Proton Pump Inhibitors (PPIs) Market. Related Reports: The tyrosine kinase inhibitors market is estimated to grow at a CAGR of 8.93% between 2022 and 2027. The market size is forecasted to increase by USD 24.12 billion. The global PARP (poly ADP-ribose polymerase) inhibitors market size is estimated to grow by USD 5,555.99 million at a CAGR of 13.25% between 2023 and 2028. What are the key data covered in this proton pump inhibitors (PPIs) market report? CAGR of the market during the forecast period Detailed information on factors that will drive the growth of the proton pump inhibitors (PPIs) market between 2023 and 2028. Precise estimation of the proton pump inhibitors (PPIs) market size and its contribution to the market in focus on the parent market Accurate predictions about upcoming trends and changes in consumer behavior Growth of the proton pump inhibitors (PPIs) market across North America, Europe, Asia, and ROW A thorough analysis of the market's competitive landscape and detailed information about vendors Comprehensive analysis of factors that will challenge the growth of proton pump inhibitors (PPIs) market vendors. ToC: Executive Summary Market Landscape Market Sizing Historic Market Sizes Five Forces Analysis Market Segmentation by Product Market Segmentation by Route of Administration Market Segmentation by Geography Customer Landscape Geographic Landscape Drivers, Challenges, & Trends Company Landscape Company Analysis Appendix About Technavio Technavio is a leading global technology research and advisory company. Their research and analysis focus on emerging market trends and provide actionable insights to help businesses identify market opportunities and develop effective strategies to optimize their market positions. With over 500 specialized analysts, Technavio's report library consists of more than 17,000 reports and counting, covering 800 technologies, spanning 50 countries. Their client base consists of enterprises of all sizes, including more than 100 Fortune 500 companies. This growing client base relies on Technavio's comprehensive coverage, extensive research, and actionable market insights to identify opportunities in existing and potential markets and assess their competitive positions within changing market scenarios. Contacts Technavio Research Jesse Maida Media & Marketing Executive US: +1 844 364 1100 UK: +44 203 893 3200 Email: [email protected] Website: SOURCE Technavio

2021-07-06

·BioSpace

Proton Pump Inhibitors Market: Omeprazole is estimated to gain higher share during the forecast period

Proton pump inhibitors are a group of medicines that reduces the gastric acid secretion in the linings of the stomach. They block the enzyme process in the gastric system that actively transports gastric acid from parietal cells to the gastrointestinal lumen in the form of hydrogen–potassium adenosine triphosphate (proton pump). Proton pump inhibitors are used to relieve the symptoms of gastro-esophageal reflux diseases (GERD), peptic ulcers, dyspepsia, gastritis, and other gastrointestinal disorders. The medicines are administered orally, and they are available in the form of capsules and tablets. Proton pump inhibitors are among the most widely used medications, due to fewer side effects. Request Brochure of Report – Increasing acceptance of novel drug delivery systems and rising prevalence of peptic ulcer and other gastro-intestinal disorders are driving the proton pump inhibitors market considerably. Consumers in isolated regions tend to prefer the common antacids to deal with ulcer & gastro-intestinal disorders, which restrains the proton pump inhibitors market. Also, the increasing use of generic drugs in the proton pump inhibitors market can hamper the growth of the market. Increasing consumer acceptance of novel drug delivery systems and launching of new products is always an opportunity for the proton pump inhibitors market. The proton pump inhibitors market can be segmented according to drug types. They are Omeprazole, Rabeprazole, Pantoprazole, Lansoprazole, Dexlansoprazole, Esomeprazole, and Others. Esomeprazole is the most widely prescribed drug for gastric ulcer in the proton pump inhibitors market. The segment dominated the proton pump inhibitors market in 2015 attributed to its potency, efficacy, and its wide distribution in the market. Dexlansoprazole & Rabeprazole were the second most widely prescribed medication types after Esomeprazole in 2015. Omeprazole is estimated to gain higher share during the forecast period, which is attributed to its availability in generic and over-the-counter form, and its cost-effectiveness. The patent license of drug Nexium (Esomeprazole) expired in the year 2015, which is the major reason for the likely domination of Omeprazole & Lansoprazole in the proton pump inhibitors market during the forecast period. Request for Analysis of COVID-19 Impact on Proton Pump Inhibitors Market – Overall, the market share of non-generic drugs has declined while the value of the generic drug market is expected to rise which can propel the proton pump inhibitor market. Continued usage of generic drugs of the Omeprazole segment is expected to raise the market share, which can surpass Nexium drug segment during the forecast period. Geographically, the proton pump inhibitors market has been segmented into North America, Europe, Asia Pacific, Latin America, and Middle East & Africa. North America had the dominant market share in 2015, which is attributed to increase in prevalence of gastrointestinal disorders in the region and consistent launch of new products. However, the Asia Pacific market is estimated to grow at a higher CAGR by 2016- 2024. The Asia Pacific market is flooded with many gastrointestinal drug products and there is a large patient pool with gastro intestinal problems. This can create a need for curative drugs and this is anticipated to drive the proton pump inhibitors market in the region remarkably. Pre Book Proton Pump Inhibitors Market Report at – The major players in the proton pump Inhibitors market are AstraZeneca, Takeda Pharmaceuticals, Wyeth Pharmaceuticals, Eisai Pharmaceuticals India Pvt. Ltd., Teva Pharmaceuticals, Cadila Pharmaceuticals, Pfizer, Eli Lilly and Company, and Janssen Global Services, LLC. Consistent launching of new products is the strategy followed by key players to deal with the competition in the proton pump inhibitors market. About Us Transparency Market Research is a next-generation market intelligence provider, offering fact-based solutions to business leaders, consultants, and strategy professionals. Our reports are single-point solutions for businesses to grow, evolve, and mature. Our real-time data collection methods along with ability to track more than one million high growth niche products are aligned with your aims. The detailed and proprietary statistical models used by our analysts offer insights for making right decision in the shortest span of time. For organizations that require specific but comprehensive information we offer customized solutions through ad hoc reports. These requests are delivered with the perfect combination of right sense of fact-oriented problem solving methodologies and leveraging existing data repositories. TMR believes that unison of solutions for clients-specific problems with right methodology of research is the key to help enterprises reach right decision. Contact Mr. Rohit Bhisey Transparency Market Research State Tower, 90 State Street, Suite 700, Albany NY - 12207 United States USA - Canada Toll Free: 866-552-3453 Email: sales@transparencymarketresearch.com Website:

仿制药

2021-04-17

·精准药物

【JMC】归纳近20年2000多个药物的INNs命名信息，揭示药物的化学结构趋势

JMC 杂志的最新一篇综述文章，归纳了近20年的2000个药物的命名背后的信息，揭示了药物的结构规律和趋势。世界卫生组织 (WHO) 根据药物开发人员的要求，为化合物指定国际非专利药名（international nonproprietary names ，INN），也称为药物的通用名。INNs的命名结构是公开的，分析其变化规律，可以帮助我们了解药物研究和开发的趋势。通用名，也称为药物的通用名。INNs的命名结构是公开的，分析其变化规律，可以帮助我们了解药物研究和开发的趋势。在许多国家，同一种药物销售时有多个品牌名称，这些品牌名称因国家而异。虽然化学家可能认为国际纯化学和应用化学联合会（IUPAC）的名称代表唯一的标识符，但这些名称很复杂，几乎不可能为普通公众记住，而且容易出错。因此，需要一个简短易读的通用名来识别世界各地的同一种药物。 1953年，世卫组织的理事机构世界卫生大会通过了WHA3.11号决议，由世卫组织的一个专家委员会“负责国际非专利药名（INN）的选择和批准”，并建议各国药典采用这样的名称。这一决议诞生了国际非专利药名（INN）系统，用于药物识别。它也是开发非专利药仿制药市场的一个关键支柱，在大多数国家，INNs替代了品牌名称，从而使制造商与治疗效果脱钩。其他机构也会发布行业内的命名规则，如个人护理产品委员会发布通用国际命名法化妆品成分（INCI）名称，美国国家标准协会（ANSI）发布化学品的通用名称，国际标准化组织（ISO）也有自己的命名系统。这样，一些分子会因不同的用途会被多个主体共同命名，虽然在大多数情况下这些名称是一致的，但情况并非总是如此。国际非专利药名（INNs）是如何定义的？ INN专家组由来自世界各地的专家组成，由秘书处领导和协调。专家可能包括医药化学家、药理学家、生物化学家、分子生物学家和临床医生。为了保持各领域的一致性，委员会也有一些其他学者参加，如国家命名机构和药典的代表、IUPAC专家，解剖治疗化学分类系统（ATC）代码专家等。请求INN的个人或公司可以提出一个遵守INN系统规则和惯例的名称，委员会可以接受或修改该名称。简而言之，INN的核心元素是词干，由一个或两个音节组成，通常位于药品名称的末尾。这种词干识别具有共同特征的药物，通常是作用机制，也可以是治疗用途或化学/结构特征。例如，质子泵抑制剂：奥美拉唑，埃索美拉唑，泮托拉唑，雷贝拉唑（omeprazole, esomeprazole, pantoprazole, rabeprazole）都有共同的词干拉唑（prazole），用以识别“抗溃疡，苯并咪唑衍生物”。如果INN专家组不承认药物是广泛类别的一部分，它们将被指定一个唯一的词干。如果其他具有这种新特性的分子将来会有一个INN请求，那么这些分子将得到相同的结果，委员会将把它作为一个官方的词干来推广。世卫组织出版“词干书”并定期更新，可以自由查阅。在INNs中使用词干、前缀、中缀和后缀不仅词干限定了一个药名，前缀（INNs开头的一个音节）、中缀（单词中间的一个音节），或后缀（INNs末尾的一个音节）都可以用来描述药名的特征，并给读者提供信息。例如，音节-gli-表示许多用于糖尿病的药物（例如格列本脲、卡格列嗪、西他列汀、沙罗格列他嗪、罗格列酮）；注意-glifozin、-gliptin、-glitazar和-glitazone都是识别不同药物类别的词干，前缀gli-表示抗高血糖药，这是磺胺衍生物。关于INN专家组自2000年以来最常用的词干，见下表1：编号 alkaloids and organic bases 生物碱和有机碱 tyrosine kinase inhibitors 酪氨酸激酶抑制剂 enzyme inhibitors 酶抑制剂 antivirals (undefined group 抗病毒 antihyperglycaemics 抗高血糖药 ketones 酮 immunomodulators, both stimulant/suppressive and stimulant 免疫调节剂 serine/threonine kinase inhibitors 丝苏氨酸激酶抑制 phosphorus derivatives; various pharmacological categories belonging to “fos”, other than insecticides, anthelminthics, pesticides, etc 磷衍生物 phosphatidylinositol 3-kinase inhibitors, antineoplastics PI3K抑制剂，抗肿瘤药 antiallergic or anti-inflammatory, not acting as antihistaminics 抗过敏或抗炎，不起抗组胺作用 neurokinin (tachykinin) receptor antagonists 神经激肽（速激肽）受体拮抗剂 angiogenesis inhibitors 血管生成抑制剂抗肿瘤药物；有丝分裂抑制剂，微管蛋白粘合剂 cyclin dependent kinase inhibitors cyclin依赖性激酶抑制剂阿拉伯呋喃酰基衍生物；核苷抗病毒或抗肿瘤药物，阿糖胞苷或氮胞苷衍生物内皮素受体阻滞剂抗菌药物，萘啶酸衍生物系统性抗真菌药物，咪康唑衍生物 prostaglandins 前列腺素囊性纤维化跨膜调节器（CFTR）蛋白调节剂、校正剂和放大器烟碱型乙酰胆碱受体部分激动剂抗肿瘤药物，拓扑异构酶I抑制剂 analgesics 止痛药鸟苷酸环化酶激活剂和刺激剂腺苷A受体激动剂 poly-ADP-Ribose polymerase inhibitors PARP抑制剂支气管扩张剂，苯乙胺衍生物加压素受体拮抗剂近20年来INNs药物化学分析本文收集2000-2021将SCE (small chemical entities ，小分子化学实体)， small chemical entities (small chemical entities ，小分子化学实体)，并细分为两个大小相似的子集进行数据分析，其中2000年至2011年的 A期由1038个SCE组成，2012年至2021年的 B期由980个SCE组成： SCEs药物类别的发展趋势酪氨酸激酶、细胞周期蛋白依赖性激酶、丝氨酸/苏氨酸激酶和磷脂酰肌醇3激酶抑制剂在过去10年中引起了开发人员的极大兴趣。自2011年以来，几乎20%的SCE属于这四类，其中酪氨酸激酶抑制剂占了大多数。而 37种丝氨酸/苏氨酸激酶抑制剂中，迄今没有一种得到批准。在肿瘤学领域，一些化疗类药物并没有完全过时（例如，-bulin，-abine），而另一些药物（-tecan）则完全不受欢迎。糖尿病领域和一些药物靶点（如神经激肽受体、血管加压素受体和内皮素受体）的INN分配显著下降。一个专门为一种罕见疾病（囊性纤维化）开发的药物类别在过去10年中引起了足够的兴趣，发行了12个名称（-caftor）。图6 最常见词干的频率 A期（蓝色；2000-2011年：N=1038）和B期（橙色；2012-2021年：N=980）元素组成绝大多数化合物中都含有碳、氢、氧和氮（CHON）； CHON之后，氟取代氯和硫成为CHON之后最常见的元素，30%以上化合物中含氟；碘只存在于19种化合物中，硼存在于14个分子中。含碘分子的批准率较低（11%），而含硼分子的批准率显著高基准（20%）。在14个含硼分子中，有9个在B期，表明这种元素的使用量在增加。虽然这些分子中大部分都存在硼酸（N=8），但四个分子含有五元硼杂环，两个含有六元硼杂环。其余元素为铂（N=5）、硅（N=3）、铁（N=3）、钯（N=2）、锰（N=2）、铋（N=1）、tin（N=1）、砷（N=1），含有这些不常见元素的分子如图所示。元素组成比较 A期（蓝色；2000-2011年：N=1038）和B期（橙色；2012-2021年：N=980）官能团最常见的基团是醚键（N=962），其次是酰胺、内酰胺（N=840，42%）、脂肪族胺（伯胺、仲胺和叔胺；N=797，39%）和芳香胺（N=633，31%）。药物设计中通常避免使用酯键，由于其水解不稳定性，但10%的INN分子含有该官能团。含硫官能团在这两个时期的SCE数量相同，但硫醚的使用减少，磺酰胺的使用略有增加，砜的使用急剧增加。 α，β-不饱和羰基在B期减少，α，β-不饱和酰胺在同一时期略有增加。官能团变化趋势 A期（蓝色；2000-2011年：N=1038）和B期（橙色；2012-2021年：N=980）羧酸和脂肪胺的用量都有小幅下降，我们研究酸性、碱性、中性、两性离子化合物的比例发现，中性47%；碱性27%；酸性19%；两性离子7%；随着时间的推移，中性SCE略有增加，从A期平均43%的中性药物上升到B期的51%。中性、酸性、碱性和两性离子SCE的分布 A期（蓝色；2000-2011年：N=1038）和B期（橙色；2012-2021年：N=980）环系统从方法学的观点来看，所有的环和稠环都被保留，还有内环键和外环羰基、磺酰基、亚胺、亚砜基和硫羰基。总体上，我们在A期和B期分别发现362和419个不同的环系统，其中A、B期分别有224和257个环系统仅用于单个SCE，表明化学新颖性正在增加。大多数含氮芳香环系统更多地出现在周期B中：吡啶、苯并咪唑和吡嗪增加了一倍，嘧啶几乎增加了三倍；吲唑尽管数量很少，但随着时间的推移正经历着显著的增加。这可能主要归因于酪氨酸激酶抑制剂（-tinib）的出现，它们的药效团中通常含有腺嘌呤模拟骨架。含氮的脂肪环，包括氮杂环丁烷、吡咯烷和吗啡以及哌啶和哌嗪也在增加，尽管程度较小；这些子结构都越来越频繁地被用作增强溶解度。尽管1,2,4-三唑呈稳定趋势，但由于点击化学方法的出现及其在药物开发中的应用（A期N=3；B期N=12），1,2,3-三唑尽管不在前30名之列，但仍在显著增加。环系统变化 A期（蓝色；2000-2011年：N=1038）和B期（橙色；2012-2021年：N=980）蓝色 A期（蓝色；2000-2011年：N=1038）和B期（橙色；2012-2021年：N=980）橙色 A期（蓝色；2000-2011年：N=1038）和B期（橙色；2012-2021年：N=980）对称化合物大量的对称化合物令人印象深刻（N=29），在过去的20年里，这些分子的数量翻了一番，从2000年到2011年的10个增加到了过去10年的19个。两种化合物实际上是前药，含有一个失活部分和两个相同的活性成分分子（碳酸洛地那非、癸二酸二丁啡）。大多数其他对称化合物是设计用于靶向二聚体结构的蛋白质的传统双药。化学诱导二聚体（CID）技术导致rimiducid的出现。代表性对称化合物的结构分子复杂性人们通常认为，由于药物靶标的挑战和合成可及性，药物分子正变得越来越复杂。分子量：更大、更复杂的分子能够进入更大的化学空间，能够更好地调控靶蛋白三维结合位点。B期药物的MW比A期药物的MW高出10%。尽管MW正在增加，MW低于300的类药分子仍然具有较多的成药机会，2011-2016年间17%的药物MW小于300。我们也发现大量化合物的MW低于150，其中五种是世界范围内批准的新药。虽然MW500被认为是类药物化合物的阈值，但29%的INN化合物高于此限值，其中11.5%的INN为大环化合物（N=69）。分子量低于150da的12个sce的结构手性：在批准的药物中，64%的药物至少有一个立体中心，A/B期化合物数量相当。在同一时期，每个SCE的平均立体中心数则略有下降。8个SCE的立体中心数等于或大于20个，其中伊维尼米星的立体中心数最多为35个，其次是匹沙莫德有29个立体中心。手性SCE的批准率为27%，略高于20%的平均值，在纯立体异构体（28%）和立体异构体混合物（26%）中没有差异。螺环：得益于合成策略的最新进展，螺环被引入了更多分子结构。虽然环丙烷在药物研发中已应用多年，但环丁烷、氮杂环丁烷和氧杂环丁烷直到最近才流行起来。Bauer等人总结，环丙烷是最常用的小环，其次是环丁烷、氮杂环丁烷和氧杂环丁烷。尽管数量很少，但除了氧杂环丁烷外，所有环的使用随时间而增加，环丙烷的增长最为显著。有趣的是，环丁烷在2000-2007年期间没有出现，2008年开始出现，此后出现了15次。含有螺环和小环的代表性药物本文分析了2000年至2021年间的药物命名规律，发现一些化学结构的变化，如氟和杂环化合物的使用显著增加，分子量的逐渐增加，螺旋环支架和小环的增加，非传统结构的出现等，这些有可能预示药物的未来趋势。虽然INNs数据库非常有助于审查正在开发的药物，并告知药物化学的趋势，但它不太可能永远赋予一个分子的成功特征，因为太多的变量及人的能动性会改变药物的未来样子。

小分子药物

100 项与雷贝拉唑钠/甲硝唑/阿莫西林相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	雷贝拉唑钠/甲硝唑/阿莫西林	J01CR02	DB01129

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
胃炎	日本	Eisai Co., Ltd.	2013-11-21
十二指肠溃疡	日本	Eisai Co., Ltd.	2013-08-15
幽门螺杆菌感染	日本	Eisai Co., Ltd.	2013-08-15
免疫性血小板减少症	日本	Eisai Co., Ltd.	2013-08-15
胃溃疡	日本	Eisai Co., Ltd.	2013-08-15

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
哮喘	临床3期	美国	Eisai, Inc.	2002-09-01
胃食管反流	临床3期	美国	Eisai, Inc.	2002-09-01
消化不良	临床2期	日本	Eisai Co., Ltd.	2010-04-01
鼻咽疾病	临床2期	美国	Eisai, Inc.	2002-06-01

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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


DDW2024	N/A	一线	720	14-day vonoprazan triple therapy	艱獵廠鹹膚鹹觸壓繭餘(積糧願餘構構網蓋積鹹) = 窪膚鹽簾餘繭網構蓋製醖願憲積顧窪築壓廠夢 (餘範獵製膚範觸窪網淵, 90.1 ~ 96.5)	积极	2024-05-18
				14-day vonoprazan high-dose dual therapy	艱獵廠鹹膚鹹觸壓繭餘(積糧願餘構構網蓋積鹹) = 製鏇餘觸願糧膚膚艱顧醖願憲積顧窪築壓廠夢 (餘範獵製膚範觸窪網淵, 82.0 ~ 90.6)
UEGW2019	N/A	幽门螺杆菌感染	-	Quadruple therapy 10 days (QT-10)	膚網鏇淵蓋選觸願觸鹹(襯憲構衊構範範積膚衊) = The overall incidence of AEs was also significantly lower in the OST-14 group, compared to QT-10 and QT-14 groups (21.2%, 37.2% and 41.6% respectively, p=0.02 ) 願積衊願艱餘蓋窪製簾 (鬱顧鏇網襯繭鹹齋艱顧 )	积极	2019-10-01
NCT02135107 (EXTEND, CTgov)	临床3期	胃食管反流	517	Rabeprazole (Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Once Daily)	願膚範遞蓋鹹網繭觸衊 = 餘襯廠憲鹽憲製繭網製鬱製簾鏇廠餘鹹遞鏇選 (顧憲網衊選憲餘鏇願鹽, 廠餘夢鑰餘蓋範窪願簾 ~ 製齋齋遞網積簾遞壓製) 更多	-	2018-11-19
				Rabeprazole (Rabeprazole: 10 or 20 mg Twice Daily, Then 10 mg Twice Daily)	願膚範遞蓋鹹網繭觸衊 = 膚觸鏇範艱網鹽築構觸鬱製簾鏇廠餘鹹遞鏇選 (顧憲網衊選憲餘鏇願鹽, 艱鏇壓遞觸網蓋觸壓觸 ~ 顧積獵鏇鬱網襯築鬱範) 更多
NCT02135107 (EXTEND, Pubmed \| J Gastroenterol)	临床3期	反流性食管炎维持	517	Rabeprazole 10 mg q.d.	淵廠齋壓網築選鬱廠壓(夢淵簾鏇網窪窪顧艱觸) = 獵壓窪窪簾構醖鬱繭構淵構願鹹鏇憲餘窪觸觸 (壓鑰襯鹽鑰選顧築鹹製 )	-	2018-07-01
				Rabeprazole 10 mg b.i.d.	淵廠齋壓網築選鬱廠壓(夢淵簾鏇網窪窪顧艱觸) = 範蓋鹽鹹蓋餘願襯鬱憲淵構願鹹鏇憲餘窪觸觸 (壓鑰襯鹽鑰選顧築鹹製 )
NCT01398410 (CTgov)	临床2/3期	胃溃疡	405	Rabeprazole (Rabeprazole 5 mg)	範鬱願網築願積蓋願襯 = 遞醖醖築觸觸鏇醖觸遞顧淵蓋簾製鏇繭繭獵襯 (遞壓鑰鏇獵構鬱觸製醖, 齋衊鹽鏇構淵餘獵襯齋 ~ 淵網觸鹹廠壓餘鹽簾醖) 更多	-	2015-11-16
				Rabeprazole (Rabeprazole 10 mg)	範鬱願網築願積蓋願襯 = 糧鹽蓋蓋艱淵獵鏇憲構顧淵蓋簾製鏇繭繭獵襯 (遞壓鑰鏇獵構鬱觸製醖, 壓簾鑰蓋夢鏇淵顧遞顧 ~ 鏇構繭餘繭廠憲鬱鏇窪) 更多
NCT00839306 (CTgov)	临床3期	胃食管反流	240	RAN (RAN 150mg BID)	廠鏇積糧窪鬱膚淵遞鬱 = 鏇鬱範膚鏇膚餘淵鬱鬱遞選鹽鬱餘構艱糧繭鑰 (選餘淵憲築觸顧範膚選, 廠鹹衊觸鑰衊範鬱鑰餘 ~ 觸鑰壓襯壓鹽範範獵壓) 更多	-	2015-11-16
				RAB (RAB ER 50mg QD)	廠鏇積糧窪鬱膚淵遞鬱 = 鏇遞蓋齋艱簾醖窪鹽鏇遞選鹽鬱餘構艱糧繭鑰 (選餘淵憲築觸顧範膚選, 顧遞繭製製淵鬱鏇鬱網 ~ 壓獵膚築窪獵壓繭醖窪) 更多
NCT00838526 (CTgov)	临床3期	胃食管反流	240	RAN (RAN 150mg BID)	糧簾獵顧夢衊蓋衊廠製 = 醖繭鏇鏇襯蓋鬱繭鏇範襯壓窪淵顧淵蓋簾積築 (餘顧簾獵醖糧積範艱繭, 衊齋築壓願積觸築窪壓 ~ 醖衊簾製鏇餘廠獵築衊) 更多	-	2015-06-23
				RAB (RAB ER 50mg QD)	糧簾獵顧夢衊蓋衊廠製 = 鏇糧鬱窪鬱構遞網範獵襯壓窪淵顧淵蓋簾積築 (餘顧簾獵醖糧積範艱繭, 窪齋網範餘範餘繭鏇淵 ~ 壓鬱鹽憲遞憲醖齋鹽壓) 更多
NCT00539240 (CTgov)	临床2/3期	疼痛 \| 胃食管反流	236	placebo+Rabeprazole+AciPhex (Arm 1)	獵願衊願積壓夢範製糧(鬱醖鬱製鏇願築鏇構窪) = 鏇顧獵艱窪築積選醖獵衊糧範積顧鹽艱醖膚觸 (淵蓋膚積艱艱齋鹽觸窪, 0.9) 更多	-	2014-08-18
				placebo+Rabeprazole+AcipHex (Arm 2)	獵願衊願積壓夢範製糧(鬱醖鬱製鏇願築鏇構窪) = 獵齋蓋顧鏇觸遞製簾蓋衊糧範積顧鹽艱醖膚觸 (淵蓋膚積艱艱齋鹽觸窪, 2.2) 更多
NCT00787891 (Pubmed \| J Pediatr Gastroenterol Nutr)	临床3期	胃食管反流	127	Rabeprazole 0.5-mg/kg	遞積衊鹽鬱網觸齋窪壓(醖範糧簾糧簾蓋壓鏇衊) = 12% 積願網窪窪構淵選鏇觸 (鏇簾鑰築網顧鏇齋夢窪 ) 更多	积极	2013-12-01
NCT01089543 (SAMURAI \| E3810-J081-204, CTgov)	临床2期	消化不良	338	Rabeprazole (Rabeprazole 10 mg)	鹽鏇繭網網衊夢壓壓鹽 = 觸積顧選醖繭構築觸艱繭夢艱壓壓餘製艱窪窪 (廠鑰鬱顧遞鏇製選鏇膚, 艱憲遞範選艱壓憲醖艱 ~ 鹽夢憲餘壓壓衊網糧艱) 更多	-	2013-11-19
				Rabeprazole (Rabeprazole 20 mg)	鹽鏇繭網網衊夢壓壓鹽 = 選築遞憲衊顧鏇鹹鹹製繭夢艱壓壓餘製艱窪窪 (廠鑰鬱顧遞鏇製選鏇膚, 憲壓鑰襯選構獵選壓糧 ~ 構製選壓顧鏇顧顧餘蓋) 更多