Drug Target Insights最新文献_第6页

A Comprehensive Review of Pegvaliase, an Enzyme Substitution Therapy for the Treatment of Phenylketonuria. peg - valiase，一种治疗苯丙酮尿的酶替代疗法的综合综述。

IF 2.7

Drug Target Insights Pub Date : 2019-06-21 eCollection Date: 2019-01-01 DOI: 10.1177/1177392819857089

Tasmina Hydery, Valerie Azzopardi Coppenrath

{"title":"A Comprehensive Review of Pegvaliase, an Enzyme Substitution Therapy for the Treatment of Phenylketonuria.","authors":"Tasmina Hydery, Valerie Azzopardi Coppenrath","doi":"10.1177/1177392819857089","DOIUrl":"https://doi.org/10.1177/1177392819857089","url":null,"abstract":"Objective: To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of a phenylalanine-metabolizing enzyme indicated to reduce blood phenylalanine concentrations, pegvaliase injection.Data sources: Searches of MEDLINE (1946-September 1, 2018) were conducted using the terms pegvaliase and phenylalanine ammonia lyase (PAL). Additional data were obtained from the prescribing information, the product dossier obtained from the manufacturer, and Clinicaltrials.gov.Study selection and data extraction: All English language articles related to pharmacology, pharmacokinetics, efficacy, or safety of the combination therapy in human subjects were reviewed.Data synthesis: Pegvaliase is a pegylated PAL enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. Blood phenylalanine levels were reduced by approximately 50% to 70% in patients receiving therapeutic doses of pegvaliase. However, most patients experienced adverse events.Conclusions and relevance: The mainstay of therapy in phenylketonuria (PKU) has historically consisted of dietary restriction of phenylalanine. Pegvaliase injection is the first Food and Drug Administration (FDA)-approved enzyme substitution therapy for patients with PKU. The therapy may be a viable option for patients with documented blood phenylalanine >600 µmol/L who have failed existing management strategies.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"13 ","pages":"1177392819857089"},"PeriodicalIF":2.7,"publicationDate":"2019-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177392819857089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37377373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 32

Omalizumab as a Provoking Factor for Venous Thromboembolism 奥马珠单抗作为静脉血栓栓塞的诱发因子

IF 2.7

Drug Target Insights Pub Date : 2019-01-01 DOI: 10.1177/1177392819861987

C. Oblitas, F. Galeano-Valle, Laura Vela-De La Cruz, J. del Toro-Cervera, P. Demelo-Rodríguez

{"title":"Omalizumab as a Provoking Factor for Venous Thromboembolism","authors":"C. Oblitas, F. Galeano-Valle, Laura Vela-De La Cruz, J. del Toro-Cervera, P. Demelo-Rodríguez","doi":"10.1177/1177392819861987","DOIUrl":"https://doi.org/10.1177/1177392819861987","url":null,"abstract":"A 43-year-old man with a history of severe extrinsic allergic asthma treated with once-monthly omalizumab (600 mg) for the last 15 months. He presented to the emergency room with a 2-week history of right lower limb pain and chest pleuritic pain. Computed tomography pulmonary angiography showed bilateral pulmonary embolism with right-sided pulmonary infarction and ultrasound of right lower limb confirmed distal deep vein thrombosis. No other known risk factors were identified. Treatment with omalizumab was stopped during hospitalization. The Naranjo Adverse Drug Reaction (ADR) Probability Scale classifies this as a probable ADR (score of 6). Omalizumab is a humanized monoclonal anti-IgE antibody indicated for the treatment of persistent moderate-to-severe asthma and certain chronic refractory urticaria. The EXCELS study (The Epidemiologic Study of Xolair (omalizumab): Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate-to-Severe Asthma), a postmarketing observational cohort study to assess clinical safety profile of omalizumab, showed a significant increase in venous thromboembolism. In conclusion, omalizumab has been associated with arterial and venous thromboembolic events, although the evidence is not definitive.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177392819861987","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47878471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Vernakalant in Atrial Fibrillation: A Relatively New Weapon in the Armamentarium Against an Old Enemy Vernakalant在房颤中的作用:对抗老敌人的一种相对较新的武器

IF 2.7

Drug Target Insights Pub Date : 2019-01-01 DOI: 10.1177/1177392819861114

A. Kossaify

{"title":"Vernakalant in Atrial Fibrillation: A Relatively New Weapon in the Armamentarium Against an Old Enemy","authors":"A. Kossaify","doi":"10.1177/1177392819861114","DOIUrl":"https://doi.org/10.1177/1177392819861114","url":null,"abstract":"Atrial fibrillation is the most common sustained cardiac arrhythmia, and its prevalence is increasing with age; also it is associated with significant morbidity and mortality. Rhythm control is advised in recent-onset atrial fibrillation, and in highly symptomatic patients, also in young and active individuals. Moreover, rhythm control is associated with lower incidence of progression to permanent atrial fibrillation. Vernakalant is a relatively new anti-arrhythmic drug that showed efficacy and safety in recent-onset atrial fibrillation. Vernakalant is indicated in atrial fibrillation (⩽7 days) in patients with no heart disease (class I, level A) or in patients with mild or moderate structural heart disease (class IIb, level B). Moreover, Vernakalant may be considered for recent-onset atrial fibrillation (⩽3 days) post cardiac surgery (class IIb, level B). Although it is mainly indicated in patients with recent-onset atrial fibrillation and with no structural heart disease, it can be given in moderate stable cardiac disease as alternative to Amiodarone. Similarly to electrical cardioversion, pharmacological cardioversion requires a minimal evaluation and cardioversion should be included in a comprehensive management strategy for better outcome.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"13 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177392819861114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42796524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Bacopa monnieri, a Neuroprotective Lead in Alzheimer Disease: A Review on Its Properties, Mechanisms of Action, and Preclinical and Clinical Studies 假马齿苋:阿尔茨海默病的神经保护铅:其特性、作用机制及临床前和临床研究综述

IF 2.7

Drug Target Insights Pub Date : 2019-01-01 DOI: 10.1177/1177392819866412

Aimi Syamima Abdul Manap, S. Vijayabalan, P. Madhavan, Y. Y. Chia, A. Arya, E. H. Wong, Farzana Rizwan, U. Bindal, Shajan Koshy

引用次数: 62

DRESS Syndrome and Daclizumab Failure-Were Potentially Dangerous Signs Missed in Clinical Trials? DRESS综合征和达珠单抗失效是临床试验中遗漏的潜在危险体征吗？

IF 2.7

Drug Target Insights Pub Date : 2018-06-29 DOI: 10.1177/1177392818785136

Jagannadha Avasarala

{"title":"DRESS Syndrome and Daclizumab Failure-Were Potentially Dangerous Signs Missed in Clinical Trials?","authors":"Jagannadha Avasarala","doi":"10.1177/1177392818785136","DOIUrl":"10.1177/1177392818785136","url":null,"abstract":"The US Food and Drug Administration (FDA) approved Zinbryta, an interleukin-2 receptor blocking antibody (daclizumab; Biogen and AbbVie) for the treatment of adults with relapsing forms of multiple sclerosis (MS) in May, 2016. It was also approved by the European Union in July, 2016. Zinbryta is a long-acting, self-administered monthly injection that was branded as a new MS drug for patients who needed a \"new option for treatment.\" It blocks interleukin-2 receptor alpha (CD25) and modulates T-cell expansion. The drug was withdrawn from the market in March, 2018 following 12 reports from Germany (9), United States (2), and Spain (1) following the development of \"inflammatory encephalitis and meningoencephalitis\" in patients on Zinbryta. Although cases of hepatotoxicity made news with Zinbryta earlier along this drug's postmarketing journey in the treatment of patients with MS, the European Medicines Agency (EMA) ordered a review of the risks of hepatotoxicity with Zinbryta use June, 2017; this analysis will focus on the pharmacovigilance data concerning the central nervous system (CNS) complications. The details of the CNS complications have been elucidated by EMA. Every drug failure provides an opportunity for learning, but it is also noteworthy that no FDA-approved MS drug in modern times has met with such an untimely, sudden, and inglorious exit. This should serve as a cautionary tale for all clinicians who use \"newer MS drugs\" that have mushroomed in recent memory following a flurry of recent FDA approvals.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"12 ","pages":"1177392818785136"},"PeriodicalIF":2.7,"publicationDate":"2018-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177392818785136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36318019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Valacyclovir Neurotoxicity and Nephrotoxicity in an Elderly Patient Complicated by Hyponatremia. 缬昔洛韦对老年低钠血症患者的神经毒性和肾毒性。

IF 2.7

Drug Target Insights Pub Date : 2018-06-25 eCollection Date: 2018-01-01 DOI: 10.1177/1177392818782899

Takuya Murakami, Tetsu Akimoto, Mari Okada, Erika Hishida, Taro Sugase, Atsushi Miki, Marina Kohara, Hiromichi Yoshizawa, Takahiro Masuda, Takahisa Kobayashi, Osamu Saito, Shigeaki Muto, Daisuke Nagata

{"title":"Valacyclovir Neurotoxicity and Nephrotoxicity in an Elderly Patient Complicated by Hyponatremia.","authors":"Takuya Murakami, Tetsu Akimoto, Mari Okada, Erika Hishida, Taro Sugase, Atsushi Miki, Marina Kohara, Hiromichi Yoshizawa, Takahiro Masuda, Takahisa Kobayashi, Osamu Saito, Shigeaki Muto, Daisuke Nagata","doi":"10.1177/1177392818782899","DOIUrl":"https://doi.org/10.1177/1177392818782899","url":null,"abstract":"A 66-year-old women with no history of renal disease was admitted due to a coma and acute kidney injury with a serum creatinine level of 7.44 mg/dL which were ascribed to valacyclovir neurotoxicity and nephrotoxicity, respectively. She had received valacyclovir at a standard dosage for the treatment of herpes zoster and was finally discharged, having fully returned to her normal baseline mental status with a recovered serum creatinine level of 0.68 mg/dL. We feel that awareness of this pathology remains a challenge for physicians and therefore strongly recommend the further accumulation of experiences similar to our own. Our experience underscores the pitfalls of administering valacyclovir to elderly patients who barely appear to have a favorable renal function. Several concerns regarding the therapeutic management, including blood purification strategies, that emerged in this case are also discussed.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"12 ","pages":"1177392818782899"},"PeriodicalIF":2.7,"publicationDate":"2018-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177392818782899","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36318018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Anti-CD20 Cell Therapies in Multiple Sclerosis-A Fixed Dosing Schedule for Ocrelizumab is Overkill. 抗cd20细胞治疗多发性硬化症- Ocrelizumab的固定剂量计划是过度杀伤。

IF 2.7

Drug Target Insights Pub Date : 2017-10-25 eCollection Date: 2017-01-01 DOI: 10.1177/1177392817737515

Jagannadha Avasarala

{"title":"Anti-CD20 Cell Therapies in Multiple Sclerosis-A Fixed Dosing Schedule for Ocrelizumab is Overkill.","authors":"Jagannadha Avasarala","doi":"10.1177/1177392817737515","DOIUrl":"https://doi.org/10.1177/1177392817737515","url":null,"abstract":"Anti-CD 20 therapies have found significant uses in multiple sclerosis (MS). Based singularly on the accumulated evidence with the use of rituximab (RTX; Rituxan, Genentech, and Biogen) in neuroimmunological diseases, ocrelizumab (OCR; Ocrevus, Genentech) was developed as a treatment option for MS and selectively targets CD20 B cells, a cell surface antigen found on pre-B cells, mature, and memory B cells, but not on lymphoid stem cells and plasma cells. On the basis of indirect evidence, elimination of the antigen-presenting capabilities and antigen nonspecific immune functions of B cells appear to be central to the therapeutic efficacy of anti-CD20 B-cell therapies. An important question is this-Why does the drug need to be dosed at fixed intervals and not based on a measurable endpoint, such as tracking peripheral CD20 cell counts? There is minimal scientific validity in infusing the drug every 6 months particularly if CD20 cell counts are negligible in the peripheral blood. In this analysis, a case is made for following CD19 cell populations as a surrogate for CD20 cells on a monthly basis to guide OCR redosing parameters and does not follow a scheduled dosing parameter.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"11 ","pages":"1177392817737515"},"PeriodicalIF":2.7,"publicationDate":"2017-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177392817737515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35594183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Ethanol Extract of Stem Bark Show Remarkable Prophylactic Activity in Experimental –Infected Mice 茎皮乙醇提取物对实验性感染小鼠有显著的预防作用

IF 2.7

Drug Target Insights Pub Date : 2017-08-28 DOI: 10.4137/DTI.S42761

Olayinka O Otegbade, J. Ojo, D. Adefokun, O. Abiodun, B. Thomas, O. Ojurongbe

引用次数: 0

Ethanol Extract of Blighia sapida Stem Bark Show Remarkable Prophylactic Activity in Experimental Plasmodium berghei-Infected Mice. 树皮乙醇提取物对实验性疟原虫感染小鼠有显著的预防作用

IF 2.7

Drug Target Insights Pub Date : 2017-08-28 eCollection Date: 2017-01-01 DOI: 10.1177/1177392817728725

Olayinka O Otegbade, Johnson A Ojo, Dolapo I Adefokun, Oyindamola O Abiodun, Bolaji N Thomas, Olusola Ojurongbe

{"title":"Ethanol Extract of Blighia sapida Stem Bark Show Remarkable Prophylactic Activity in Experimental Plasmodium berghei-Infected Mice.","authors":"Olayinka O Otegbade, Johnson A Ojo, Dolapo I Adefokun, Oyindamola O Abiodun, Bolaji N Thomas, Olusola Ojurongbe","doi":"10.1177/1177392817728725","DOIUrl":"10.1177/1177392817728725","url":null,"abstract":"This work explores the antiplasmodial potential of ethanol extract of Blighia sapida (Lin. Sapindaceae) in chloroquine (CQ)-resistant Plasmodium berghei (ANKA strain)-infected mice. Chloroquine-resistant (ANKA) strain of P berghei was inoculated intraperitoneally into Swiss albino mice. Mice were treated orally for 4 consecutive days, before and after inoculation (prophylactic, suppressive, and curative models) with graded doses of the plant extracts with Artemether-Lumefantrine (Coartem) as control. Prophylactically, the extract showed a remarkable activity in the chemosuppression of P berghei parasites (P < .01) ranging from 57% to 36.5% at doses of 200 to 800 mg/kg, respectively, whereas Coartem (10 mg/kg) produced 62.1% chemosuppression. No significant chemosuppression was observed in the curative and suppressive models. The plant extract appeared to be safe at the highest dose tested (5000 mg/kg) for acute toxicity, with no adverse effect on the different organs. The plant extract possesses prophylactic antimalarial activity, which supports its use in the prevention of malaria.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"11 ","pages":"1177392817728725"},"PeriodicalIF":2.7,"publicationDate":"2017-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6e/b8/10.1177_1177392817728725.PMC5576538.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35327847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modification of S-Adenosyl-l-Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation. 登革病毒非结构蛋白5甲基转移酶抑制剂s -腺苷-l-同型半胱氨酸的分子对接和分子动力学模拟修饰

IF 2.7

Drug Target Insights Pub Date : 2017-04-20 eCollection Date: 2017-01-01 DOI: 10.1177/1177392817701726

Usman Sumo Friend Tambunan, Mochammad Arfin Fardiansyah Nasution, Fauziah Azhima, Arli Aditya Parikesit, Erwin Prasetya Toepak, Syarifuddin Idrus, Djati Kerami

{"title":"Modification of S-Adenosyl-l-Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation.","authors":"Usman Sumo Friend Tambunan, Mochammad Arfin Fardiansyah Nasution, Fauziah Azhima, Arli Aditya Parikesit, Erwin Prasetya Toepak, Syarifuddin Idrus, Djati Kerami","doi":"10.1177/1177392817701726","DOIUrl":"https://doi.org/10.1177/1177392817701726","url":null,"abstract":"Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world's population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S-adenosyl-l-methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2'OH, resulting in S-adenosyl-l-homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test. The 2 simulations were performed using Molecular Operating Environment (MOE) 2008.10 software, whereas the ADME-Tox test was performed using various software. The modification of SAH compound was done using several functional groups that possess different polarities and properties, resulting in 3460 ligands to be docked. After conducting docking simulation, we earned 3 best ligands (SAH-M331, SAH-M2696, and SAH-M1356) based on ΔGbinding and molecular interactions, which show better results than the standard ligands. Moreover, the results of molecular dynamics simulation show that the best ligands are still able to maintain the active site residue interaction with the binding site until the end of the simulation. After a series of molecular docking and molecular dynamics simulation were performed, we concluded that SAH-M1356 ligand is the most potential SAH-based compound to inhibit NS5 methyltransferase enzyme for treating dengue fever.","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"11 ","pages":"1177392817701726"},"PeriodicalIF":2.7,"publicationDate":"2017-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1177392817701726","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34966272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17