Clinical Pharmacokinetics of Cytochrome P450: Influence on the Pharmacokinetics of Naproxen (CYP2C8 and CYP2C9) and Associated Naproxen-esomeprazole (CYP2C19)

The family of cytochrome P450 (CYP) is the most important drug metabolizing enzymes which contributes to the metabolism of a large proportion of drugs in humans. Some CYP450 enzymes reduce or alter the pharmacodynamic activity of many drugs and are involved in oxidative metabolism and elimination of many drugs commonly used by the population. Polymorphisms in CYP2C8 and CYP2C9 are common in different populations around the world and genetic variations in these alleles can cause decreased enzyme activity to nonsteroidal anti-inflammatory drugs (NSAIDs) such as celecoxib, diclofenac, ibuprofen, indomethacin, lornoxicam, meloxicam, valdecoxib, piroxicam, tenoxicam and naproxen. This compromise the bioavailability of the drug can alter the pharmacokinetics of these drugs and patients with mutations in these genes can exhibit increased plasma concentrations of values and areas under the curve (AUC), in addition to decreased clearance of drugs. Associations between NSAIDs and gastric protectors or proton pump inhibitors (PPIs) have become common nowadays, especially in patients who make chronic use of these drugs. Naproxen associated to esomeprazole, a proton pump inhibitor (PPI), was launched in the market recently and its application in acute pain is not yet elucidated. Esomeprazole suffers strong influence of CYP2C19 (hepatic drug-metabolizing enzyme that degrades PPIs). In patients with high enzyme activity of the CYP2C19, the drug can suffer high enzymatic degradation, and its diminished effect. Moreover, in patients with low enzyme CYP2C19 activity, the effect of acid inhibition by PPIs can be very strong.

开始日期2017-03-01

申办/合作机构

University of Sao Paulo

[+1]

NCT02355236

/ Unknown status临床4期IIT

A Prospective, Randomized, Double-blinded, Double-dummy, Active-controlled, Multi-center, Interventional Study to Compare Gastro-protective Effect and Pain Relief Effect of Naxozol Compared to Celecoxib in Patients With Osteoarthritis

Naxozol is a combination product of naproxen, a non-steroidal anti-inflammatory drug (NSAID) and esomeprazole, a proton pump inhibitor which is designed to improve symptoms and reduce risk of gastric ulcers in patients at risk of developing NSAID-associated gastric ulcers in the treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. The purpose of this study is to investigate whether naxozol protects the gastrointestinal tract effectively compared to celecoxib, a COX-2 inhibitor.

开始日期2015-02-01

申办/合作机构

Severance Hospital

NCT02307305

/ Unknown status临床2期IIT

Does Duloxetine Reduce Chronic Pain After Total Knee Arthroplasty?

Range from 24% to 44%, with a prevalence of neuropathic-type pain from 6% to 20%-cause impairment in quality of life and functional capacity after total knee arthroplasty(TKA). Duloxetine (cymbalta) is a selective serotonin and nor-epinephrine reuptake inhibitor shown to be effective in treating chronic pain. Serotonin and norepinephrine in the brain and spinal cord are believed to both mediate core mood symptoms and help regulate the perception of pain. Its effects on depression and anxiety symptoms, as well as its effect on pain perception, may be due to increasing the activity of serotonin and norepinephrine in the central nervous system. Approved for the acute and maintenance treatment of major depressive disorder, the acute treatment of generalized anxiety disorder, the management of diabetic peripheral neuropathic pain and the management of fibromyalgia, all in adults (18+).
Investigators will compare the neuropathic pain following TKA in duloxetine group (n=84) with those in non-duloxetine group (n=84). Investigators will classify the participants in to 2 groups (duloxetine and non-duloxetine group) randomly, and primarily evaluate the degree of neuropathic pain using the S-LANSS pain scale (preoperatively and postoperatively 3 and 6 months). All participants will receive postoperative pain control after TKA using the same pain control regimen except duloxetine.

开始日期2014-08-01

申办/合作机构-

100 项与萘普生/埃索美拉唑镁相关的临床结果

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100 项与萘普生/埃索美拉唑镁相关的转化医学

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100 项与萘普生/埃索美拉唑镁相关的专利（医药）

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项与萘普生/埃索美拉唑镁相关的文献（医药）

2018-12-01·Pediatric rheumatology online journal3区 · 医学

A 6-month, multicenter, open-label study of fixed dose naproxen/esomeprazole in adolescent patients with juvenile idiopathic arthritis

3区 · 医学

ArticleOA

作者: Lovell, Daniel J ; Jerath, Rita ; Von Scheven, Emily ; Francis-Sedlak, Megan ; Naddaf, Henry ; Alpan, Oral ; Reinhardt, Adam ; Dare, Jason A ; Zeft, Andrew ; Jung, Lawrence ; LaMoreaux, Brian D ; Gottlieb, Beth ; Goldsmith, Donald ; Holt, Robert J ; Gupta, Ramesh ; Ball, Julie

BACKGROUND:

Juvenile idiopathic arthritis (JIA) is an inflammatory arthritis of unknown etiology, which lasts for greater than 6 weeks with onset before 16 years of age. JIA is the most common chronic rheumatic disease in children. NSAIDs have been the mainstay of initial management with naproxen (NAP) being commonly used, but they may cause serious side effects such as gastric ulcers which can be reduced by concomitant administration of proton pump inhibitors, such as esomeprazole (ESO).

METHODS:

Primary objective was to evaluate the safety and tolerability of 3 fixed doses of NAP/ESO in JIA patients aged 12 to 16 years. Forty-six children and adolescents with JIA by International League of Associations for Rheumatology criteria, mean age of 13.6 years, from 18 US sites were prospectively enrolled over 2 years and followed for up to 6 months. Doses of the NAP/ESO fixed combination were based on baseline weight. The exploratory efficacy outcome was assessed with the ACR Pediatric-30, - 50, - 70, - 90 Response and the Childhood Health Assessment Questionnaire (CHAQ) discomfort and functional scores at months 1, 3, and 6 as change from baseline. Occurrence and causality were assessed for treatment emergent AEs (TEAEs) and discontinuations were monitored monthly.

RESULTS:

Forty-six patients received at least 1 dose of naproxen/esomeprazole and 36 completed the trial. Thirty-seven (80.4%) had at least 1 treatment emergent adverse event (TEAE) and, with the exception of 2 events in one patient, all of the TEAEs were mild or moderate. Frequent TEAEs (≥5% of patients) were upper respiratory tract and gastrointestinal related. Eleven (23.9%) had at least 1 TEAE considered to be related to study drug. Four patients (8.7%) discontinued due to a TEAE with one of these being the only serious AE reported, acute hepatitis. Mean number of active joints at baseline was 3.1. Improvement in JIA signs and symptoms occurred at most assessments and by month 6, the percentage of patients with an ACR Pediatric-30, - 50, - 70, and - 90 Response was 47.1, 38.2, 32.4, and 17.6%, respectively. The percent of patients achieving ACR Pediatric response increased over time. CHAQ discomfort improved at each assessment and functional scores improved at all assessments for 'Arising, Walking, and Activities' with several improved for 'Dressing and Grooming, Eating, Hygiene, and Grip'. There was no indication of a dose-related efficacy effect.

CONCLUSION:

NAP/ESO was well tolerated in JIA patients aged 12 to 16 years with high levels of response to ACR criteria. No new safety signals were identified for the well-characterized components of this fixed dosed JIA treatment, which was developed to reduce the risk of gastric ulcers.

TRIAL REGISTRATION:

Clinicaltrials.gov, NCT01544114 . Registered February 21, 2012.

2016-09-01·Drug development and industrial pharmacy4区 · 医学

Novel naproxen/esomeprazole magnesium compound pellets based on acid-independent mechanism:in vitroandin vivoevaluation

4区 · 医学

Article

作者: Kan, Shuling ; Lu, Jing ; Zhao, Yi ; Liu, Jianping ; Zhang, Wenli

The purpose of this study was to develop the novel naproxen/esomeprazole magnesium compound pellets (novel-NAP/EMZ) depending on EMZ acid-independent mechanism which has been proved to be predominate in the mechanism of co-therapy with nonsteroidal anti-inflammatory drug. The novel-NAP/EMZ compound pellets, composed of NAP colon-specific pellets (NAP-CSPs) and EMZ modified-release pellets (EMZ-MRPs), were prepared by fluid-bed coating technology with desired in vitro release profiles. The resulting pellets were filled into hard gelatin capsules for in vivo evaluation in rats and compared with the reference compound pellets, consisted of NAP enteric-coated pellets (NAP-ECPs) and EMZ immediate-release pellets (EMZ-IRPs). The reference compound pellets were prepared simulating the drug delivery system of VIMOVO(®). In vivo pharmacokinetics, EMZ-MRPs had significantly larger AUC0-t (p < 0.01), 1.67 times more than that of EMZ-IRPs, and prolonged mean residence time (7.55 ± 0.12 h) than that of IRPs (1.46 ± 0.39 h). NAP-CSPs and NAP-ECPs showed similar AUC0-t. Compared to the reference compound pellets, the novel-NAP/EMZ compound pellets did not show distinct differences in histological mucosal morphology. However, biochemical tests exhibited enhanced total antioxidant capacity, increased nitric oxide content and reduced malondialdehyde level for novel-NAP/EMZ compound pellets, indicating that the acid-independent action took effect. The gastric pH values of novel-NAP/EMZ compound pellets were at a low and stable level, which could ensure normal physiological range of human gastric pH. As a result, the novel-NAP/EMZ compound pellets may be a more suitable formulation with potential advantages by improving bioavailability of drug and further reducing undesirable gastrointestinal damages.

2014-04-01·Chirality4区 · 化学

Single Enantiomer Versus Racemate: Chiral Distinction in the Proton Pump Inhibitors Omeprazole and Esomeprazole

4区 · 化学

Article

作者: Pogodin, Sergey ; Agranat, Israel ; Marom, Hili

ABSTRACT:

Chiral distinction in the proton pump inhibitor drugs omeprazole and in its chiral‐switch esomeprazole magnesium was studied employing the Density Functional Theory (DFT) method. At B3LYP/6‐311G(d,p), the 6‐methoxy∙∙∙6‐methoxy and 5‐methoxy∙∙∙5‐methoxy homochiral and heterochiral dimers were calculated. The chiral distinction free energies (ΔΔG298,(RS‐SS)) between the cyclicC2‐(S,S)‐ andCi‐(R,S)‐dimers with two intermolecular hydrogen bonds are 3.8, 1.9 (with BSSE counterpoise correction), and –6.9 (with D3 dispersion and BSSE counterpoise corrections) kJ/mol. Adding water as an implicit solvent (polarized continuum model [PCM] model) resulted in a chiral distinction energy of –3.3 kJ/mol, indicating a reversal of the order of the relative stabilities ofC2‐(S,S)‐ andCi‐(R,S)‐dimers. The chiral distinction free energies between the corresponding (less stable)C1‐dimers with one intermolecular hydrogen bond are –9.3, –5.8 (with BSSE CC), 17.6 (D3 + BSSE CC), and –3.2 (H2O) kJ/mol. The results highlight the contention that omeprazole is not just a superposition of its enantiomer constituents. They are consistent with the pharmacological evidence of enantiomer–enantiomer interactions in omeprazole versus esomeprazole and the differences between the drugs omeprazole and esomeprazole magnesium and support the lodged application for regulatory supplementary protection certificate (SPC) exclusivity for the esomeprazole‐related combination drug Vimovo.Chirality 26:214–227, 2014.© 2014 Wiley Periodicals, Inc.

项与萘普生/埃索美拉唑镁相关的新闻（医药）

2024-07-23

·Pharmaceutical Technology

Grünenthal gains Valinor Pharma and constipation drug Movantik

The acquisition aligns with Grünenthal’s strategy to expand its product portfolio. Credit: fizkes / Shutterstock. Grünenthal has announced the acquisition of US-based Valinor Pharma, along with its opioid-induced constipation (OIC) therapy Movantik, in a $250m deal which includes complete royalty obligations. The transaction will be financed using Grünenthal’s available liquidity. Movantik, known as Moventig outside the US, is an oral treatment for OIC in adults with chronic non-cancer pain. The acquisition broadens Grünenthal’s portfolio of established treatments and strengthens its growing presence in the US market. In 2023 Movantik generated gross sales exceeding $200m in the US. See Also: Merck secures FDA authorisation for Ebola vaccine Ervebo US proposes rules for drug importation from Canada Grünenthal previously acquired the therapy in Europe as part of a joint venture (JV) with Kyowa-Kirin. With the purchase of Valinor, Grünenthal now owns the worldwide rights to the product, excluding Canada. Grünenthal US president Marv Kelly stated: “We are excited to welcome Valinor and expand our portfolio offering to pain specialists with Movantik.” Since 2017, the company has added several products to its lineup, including Nebido, the European rights to Crestor and Nexium, and the worldwide rights to Vimovo, Qutenza and Zomig, with Japan as an exception for the latter two. In 2023, Grünenthal also established a JV, Grünenthal Meds, with Kyowa Kirin International. This JV manages a pain-management-focused portfolio of 13 brands. Grünenthal has invested more than €2bn in successful mergers and acquisitions. Its CEO Gabriel Baertschi stated: “As a pain specialist, Movantik is a perfect fit for Grünenthal with our existing customer base and complementary product portfolio. “The acquisition of Valinor Pharma strengthens our footprint in the United States, the most important growth market for Grünenthal.”

并购上市批准

2024-07-22

·Pharmaindustrial

Grunenthal Announces Acquisition of Valinor Pharma

Grünenthal has acquired Valinor Pharma and its product Movantik (naloxegol), with a total deal value of approx. USD 250 million, inclusive of all royalty obligations. Grünenthal will finance the transaction using available liquidity. Movantik is indicated for the oral treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain. The transaction further expands Grünenthal's portfolio of established medicines and adds to the company's growing US business. Gross sales from Movantik in the United States reached over USD 200 million in 2023. "As a pain specialist, Movantik is a perfect fit for Grünenthal with our existing customer base and complementary product portfolio,” said Gabriel Baertschi, CEO, Grünenthal. "The acquisition of Valinor Pharma strengthens our footprint in the United States, the most important growth market for Grünenthal," Baertschi added. Marv Kelly, President of Grünenthal US, commented, "We are excited to welcome Valinor and expand our portfolio offering to pain specialists with Movantik.” Grünenthal acquired the product in Europe (branded Moventig outside of the US) in 2023 as part of a joint venture with Kyowa-Kirin. The acquisition of Valinor makes Grünenthal the worldwide owner of the brand (ex-Canada). With Movantik, Grünenthal continues to execute its strategy of acquiring established medicines to expand its portfolio and increase the company's profitability. Since 2017, Grünenthal has acquired several established medicines, including Nebido, the European rights to Crestor and Nexium, as well as the global rights to Vimovo (excluding the US and Japan), Qutenza and Zomig (excluding Japan). In 2023, Grünenthal established Grünenthal Meds, a joint venture with Kyowa Kirin International, which manages a portfolio of 13 brands primarily focused on pain management. Grünenthal has invested more than EUR 2 billion in successful M&A transactions.

并购

2024-05-23

·药通社

绝地翻盘：阿斯利康的转型与管线建设

对话决策层！如何打剂型差和产品差？产品立项和开发如何塑造壁垒？创新药企业都是产品为王，产品决定一个企业的胜败。小企业的成功靠产品，中型企业的成功靠一条产品管线，而大企业的成功靠管线管理——不同管线的推陈出新、各管线内产品的生命周期维持与延续。管线强则企业强，管线差则企业弱，制药巨头亦是如此。本文以阿斯利康为例，介绍管线管理的重要性、以及管线搭建与维护的方法。因为创新乏力，管线青黄不接，阿斯特拉与捷利康在1998年进行了合并，组建了阿斯利康。通过合并与整合，两个公司的资源与能力产生了很大的协同性，并推出了洛赛克（奥美拉唑）的迭代品耐信（埃索美拉唑，奥美拉唑的一种手性单体），形成以了以消化、中枢神经、抗肿瘤、心血管，呼吸和抗感染为特色的六大管线，具体产品如下表所示：虽然合并之后，阿斯利康的管线得到了明显的强化，业绩在强化销售力量和耐信等核心产品的带动下，实现了持续、稳步增长，但是创新乏力的问题并未得到解决，专利悬崖始终是挥之不去的阴影。2010年之后，阿斯利康陷入了爆品后时代的危机——销售额下滑，产品管线青黄不接，研发管线储备不足，股价一蹶不振。在阿斯利康最黑暗的时候，辉瑞曾两次报价欲收购该公司。然而令阿斯利康更为气愤的是，辉瑞对这家百年巨头的两次报价均远远不及新生的“牛犊”艾尔建。这样的阿斯利康，要么接受被收购的命运，要么背水一战——逐步完成管线的升级与延伸。幸运的是，阿斯利康在至暗的时刻迎来了救世主——总裁Pascal Soriot和研发副总裁Mene Pangalos。Pascal Soriot霸气回绝了辉瑞的收购邀约，并放出豪言，要让阿斯利康的销售额在未来的十年里翻两倍，随后便对阿斯利康进行了大刀阔斧地改革。Mene Pangalos则提出5R决策框架，在该框架的影响下，阿斯利康的研发效率在短短几年间发生了显著的变化，研发成功率几乎翻了5倍。The 5R framework2012年10月，原罗氏首席运营官Pascal Soriot加入了阿斯利康，出任阿斯利康的CEO。2013年3月，阿斯利康制定了实现销售额恢复增长和建立科学领导者地位的战略目标，其核心内容包括以下六点：1）扭转因专利悬崖和收入下滑所致的不利局面，驱动业绩恢复增长；2）加速二期临床管线的开发，以扩充三期临床管线的规模和提升生物制品管线的潜力；3）坚定不移地推出专科药，以抹平阿斯利康在普药领域的历史优势；4）通过各地团队的共同努力和获取全球认可的科学集群，以创新和差异化定位的科研重塑阿斯利康的研发平台；5）显著性简化业务，提高生产力，建立支持长期成功的文化；6）利用商务拓展和收购机遇，强化产品管线。为了达成该战略目标，阿斯利康停掉了大量夕阳性领域的产品研发，聚焦于朝阳性的领域。在开发新分子实体的同时，也不断投资产品的生命周期管理（如，开发埃索美拉唑新剂型、新规格、新用法、新适应症、新复方、OTC等）。为了支持研发，阿斯利康大幅增加了研发投入，平均研发投入强度从2008-2012年间的16.4%，迅速提升至2013-2017年间的25.5%；为了在专利悬崖之下提振业绩，阿斯利康也大幅增加了销售投入，通过在专利悬崖效应不显著的区域市场提升销售力量来最大化产品价值。为此，该公司的平均市场&一般管理费投入强度从2008-2012年间的34.2%，迅速提高至2013-2017年间的50.2%（在跨国巨头中，几乎已是最高水平）。除此以外，阿斯利康还以“不惜血本”的态度引进、投资或收购产品或管线资产。在2013-2017年间，阿斯利康收购了Ardea Biosciences、百时美施贵宝的糖尿病业务部门、Amplimmune、Spirogen、Pearl Therap、Omthera Pharma、Definiens、ZS pharma、阿特维斯在北美的呼吸系统品牌药管线，控股了Acerta Pharma，总合同金额高达140亿美元。除了企业兼并，阿斯利康还花掉了41亿美元，用以授权引进了纳洛西醇、罗沙司他、monalizumab（phase 3）等20多个产品或研发项目。高强度的研发投入、高强度的销售费用和高频率的收购，必然导致阿斯利康的利润下跌。平均净利润水平从2008-2012年间的15.3%下降至2013-2017年间的10.7%，加之销售额的逐渐下滑，年平均净利润也从2008-2012年间的48.71亿美元下降至25.81亿美元。为此，阿斯利来不得不在2016年进行资产重组，剥离大量的非核心资产套现，以推动战略的继续执行。2016年阿斯利康集中甩出的资产：2016年2月，将高血压药非洛地平和单硝酸异山梨酯缓释片的中国权益以5亿美元卖给康哲；2016年3月，将便秘药Naloxegol的欧洲权益卖给ProStrakan，交易金额未知；2016年4月，将痛风药lesinurad的美国权益以2.65亿美元卖给Ironwood；2016年6月，将麻醉部门的区域权益以7.7亿美元转让给Aspen；2016年6月，将痛风药lesinurad的欧洲和拉美权益以2.3亿美元卖给Gruenenthal；2016年8月，将小分子感染部门以15.75亿美元卖给辉瑞；2016年7月，将tralokinumab和brodalumab以10亿美元卖给Leo pharma；2016年10月，将在研的IL-23单抗MEDI2070以15.2亿美元卖给艾尔建；2016年10月，将在研的COPD药物AZD7986以1.5亿美元卖给强生子公司；2016年10月，将Rhinocourt Aqua的美国以外权益以3.3亿美元卖给强生子公司；2016年10月，将艾塞那肽的中国权益以1亿美元卖给三生制药。通过资产重组，阿斯利康完成了二次战略聚焦，不仅大幅压缩了人员规模，而且显著提升了资产利用率和运营效率。经过资产的重组，阿斯利康仅剩下抗肿瘤、心血管&代谢、呼吸三条特色管线，2017年总销售额分别为40.42亿美元，72.66亿美元和47.06亿美元，其它无法归类、低收益或专利失效的产品，进行了集中化管理，总销售额为41.56亿美元。因为资产的大量剥离和长期的产品管线青黄不接，阿斯利康的销售收入在2017年达到2004年以来的历史低谷，仅为201.52亿美元。但相比2012年，阿斯利康不仅基本完成了产品管线的推陈出新，而且研发管线中储备了多个高潜力值的产品。经过2016年的资产重组，阿斯利康放弃了夕阳性的抗感染、消化管线，整合了心血管和糖尿病等普药管线，强化了朝阳性的抗肿瘤管线。随着管线的不断强化，阿斯利康在随后的几年里，大量甩出了老旧的产品权益或管线资产，用以套现并换取新的管线资源。除此以外，阿斯利康为了最大化资产的价值，除了生命周期管理（如奥拉帕利开发新适应症、新疗法），还将部分产品的权益授权给了其它公司。例如，将奥拉帕利的部分适应症权益授权给默沙东，让其与Keytruda形成捆绑销售，从而提升经济效益。2017年的形势虽然有了明显的好转，但仍需坚持才能达到战略意义上的成功。为此，阿斯利康在研发投入强度保持不变的前提下，大幅增加了产品引进的强度。2018-2022年间，阿斯利康的项目交易总金额达329亿美元，引进了Evusheld（Cilgavimab/tixagevimab）、Vimovo（奥美拉唑/碳酸氢钠）、Wainua（eplontersen）、Andexxa（andexanet alfa）、Enhertu（trastuzumab deruxtecan）、新冠疫苗等产品，以及Sipavibart（phase 3）、camizestrant（phase 3）、ceralasertib（phase 3）、IPH5201（phase 2）、monalizumab（phase 3）等重要研发项目。除此以外，阿斯利康在此期间还兼并了5家公司，总合同金额约为425亿美元。通过对Alexion的收购，阿斯利康不仅快速布局了罕见病，还成为了赛道的领头羊。经过10年的苦心经营，阿斯利康的变化是显而易见的。通过对老化的、非核心的产品的剥离与出售，产品管线实现了推陈，通过内部研发、投资引进、交易并购等多重方式，产品管线又实现了出新。如今的阿斯利康，不仅形成了以抗肿瘤、心血管&肾病与代谢、呼吸与免疫、疫苗与免疫、罕见病为特色的五大管线。而且还在抗肿瘤、罕见病等领域建立了领先的优势，不论是产品管线还是研发管线的稀缺性都有了显著的提升。正因为此，最近两年来，阿斯利康逐渐降低了销售投入，市场&一般管理费支出已经下降至销售额的42%左右。对于创新药企业而言，现有的产品管线只能代表过去和现在的成功，而能代表未来的是研发管线。所以，相比现有产品，研发管线是影响企业市值高低的最重要因素。根据阿斯利康2023年年报披露的数据，该公司一共有178个产品处于研发管线中，项目高度聚焦于抗肿瘤、生物制药和罕见病三大领域，其中处于开发晚期阶段的新分子实体有17个，123个新分子实体或产品生命周期管理的项目处于临床二期或三期阶段。因为阿斯利康逐渐形成了强大产品管线和研发管线，股价也一路飙升，2023年的市值已相比2014年翻了两倍有余，销售额方面，该公司2023年的总营收达458亿美元，相比2014年几乎也翻了两倍，Soriot成功兑现了他的承诺。本文作者：魏利军，北京药眼信息咨询有限公司创始人，著有《跨国药企成功启示录》和《仿制药企兴衰启示录》，本文内容来自正在撰写新书《制药企业的战略设计与产线规划》中的实例。因为内容是初稿，可能存在表达和内容的轻微偏误，欢迎广大朋友提供宝贵的意见。推荐阅读

并购临床3期临床2期

100 项与萘普生/埃索美拉唑镁相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	萘普生/埃索美拉唑镁	-	-

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
强直性脊柱炎	美国	Horizon Medicines LLC	2010-04-30
骨关节炎	美国	Horizon Medicines LLC	2010-04-30
类风湿关节炎	美国	Horizon Medicines LLC	2010-04-30

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
膝关节炎	临床3期	美国	POZEN, Inc.	2008-04-01
胃溃疡	临床3期	美国	POZEN, Inc.	2007-03-01

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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


NCT01544114 (Pubmed \| Pediatr Rheumatol Online J) 人工标引	临床4期	幼年特发性关节炎	46	naproxen/esomeprazole	觸範餘鏇醖膚願餘夢衊(遞夢觸鏇齋鏇衊鹽鏇繭) = 廠鑰廠糧壓鬱構鏇鑰構範顧餘願鹽網蓋鏇顧獵 (積鏇選築膚鏇築鏇顧簾 ) 更多	积极	2018-06-26
EULAR2018	N/A	幼年特发性关节炎	-	250 mg/20 mg nap/eso	艱顧艱簾製構膚積鏇憲(鬱遞獵窪顧選製衊願積) = 網製網齋鏇網鹹構顧遞鏇獵憲淵遞願獵繭鏇醖 (積膚顧窪窪鏇窪夢膚餘 ) 更多	-	2018-06-13
				375 mg/20 mg nap/eso	艱顧艱簾製構膚積鏇憲(鬱遞獵窪顧選製衊願積) = 構糧積憲鹽襯襯夢襯淵鏇獵憲淵遞願獵繭鏇醖 (積膚顧窪窪鏇窪夢膚餘 )
NCT01544114 (CTgov)	临床4期	幼年特发性关节炎	46	VIMOVO (VIMOVO 250 mg/20 mg)	餘鏇憲襯鏇夢襯膚鏇簾 = 製簾積鹹鬱淵範觸鏇繭壓獵遞衊獵廠觸築衊齋 (獵襯襯蓋襯齋夢積鹹壓, 獵鏇網鏇鏇願蓋鏇蓋繭 ~ 鑰憲鬱積夢襯獵蓋願醖) 更多	-	2017-10-04
				VIMOVO (VIMOVO 375 mg/20 mg)	餘鏇憲襯鏇夢襯膚鏇簾 = 夢壓積積鹽顧夢觸膚糧壓獵遞衊獵廠觸築衊齋 (獵襯襯蓋襯齋夢積鹹壓, 鏇壓壓遞遞網糧觸廠醖 ~ 遞鏇壓膚範繭醖顧鬱壓) 更多
NCT00664560 (CTgov)	临床3期	膝关节炎	614	VIMOVO+PN ((PN 400 (VIMOVO) Twice Daily))	窪襯餘餘廠窪鏇獵網餘(選襯夢壓醖築憲遞餘廠) = 醖醖衊艱積壓糧鹹選襯觸艱選憲壓淵憲構醖艱 (簾糧膚夢襯鏇鑰餘獵鬱, 26.8) 更多	-	2012-02-27
				Celebrex ((Celebrex 200 mg Once Daily))	窪襯餘餘廠窪鏇獵網餘(選襯夢壓醖築憲遞餘廠) = 憲壓鹹憲憲膚繭糧鑰夢觸艱選憲壓淵憲構醖艱 (簾糧膚夢襯鏇鑰餘獵鬱, 26.2) 更多
NCT00665431 (CTgov)	临床3期	膝关节炎	610	VIMOVO+PN ((PN 400 (VIMOVO) Twice Daily))	鹽膚醖夢鬱鹹獵鑰蓋願(獵淵艱選簾窪憲蓋艱製) = 膚構憲構網鹹積膚範廠憲選鹹願襯範築願醖廠 (夢鏇壓廠廠觸繭鏇築範, 27.5) 更多	-	2011-12-06
				Celebrex ((Celebrex 200 mg Once Daily))	鹽膚醖夢鬱鹹獵鑰蓋願(獵淵艱選簾窪憲蓋艱製) = 製鑰糧構膚艱願壓製廠憲選鹹願襯範築願醖廠 (夢鏇壓廠廠觸繭鏇築範, 25.2) 更多
NCT01129011 (CTgov)	临床3期	胃溃疡	420	Naproxen	夢鏇衊顧觸窪鏇築糧壓 = 築鹹憲範餘蓋鏇糧憲構鹽網壓夢鹽遞醖壓窪窪 (壓壓廠觸廠鹹蓋憲築積, 淵襯選築築製觸範願鏇 ~ 齋艱淵願觸淵餘遞選顧) 更多	-	2010-12-28
NCT00527787 (CTgov)	临床3期	胃溃疡	434	naproxen	膚鑰簾齋窪壓簾範鏇襯 = 衊憲餘鹹製願餘觸顧遞醖構獵蓋鏇窪製構積窪 (壓製繭鹽廠範淵艱簾鹹, 淵襯憲糧艱衊餘願選鹹 ~ 廠蓋網積糧構餘夢鹽壓) 更多	-	2010-12-28
NCT00594854 (CTgov)	临床3期	胃溃疡	20	PN+naproxen+esomeprazole (PN400 (VIMOVO))	鬱憲糧願鬱築衊繭積鑰 = 艱蓋積鬱選簾衊繭齋醖獵選廠糧積築構獵網廠 (鏇鹹餘艱廠製遞糧鏇鏇, 醖網鹽築顧繭膚網選網 ~ 糧選襯夢廠觸齋製鏇顧) 更多	-	2010-09-22
				misoprostol+diclofenac (Arthrotec)	鬱憲糧願鬱築衊繭積鑰 = 鏇醖選壓製鏇獵願鬱範獵選廠糧積築構獵網廠 (鏇鹹餘艱廠製遞糧鏇鏇, 壓齋鏇鹽壓選壓鬱壓範 ~ 鏇鹽鬱憲廠膚壓簾憲襯) 更多
NCT00527904 (CTgov)	临床3期	胃溃疡	239	PN+naproxen+esomeprazole	網齋鑰鹹夢獵遞艱製廠 = 築簾鑰網艱壓範艱糧選醖積鏇願憲襯淵製簾鏇 (網鹽淵鹹膚範願夢齋窪, 顧鬱鏇鹹壓製鏇艱顧窪 ~ 壓糧壓齋壓製窪鏇餘簾) 更多	-	2010-08-20