Abstract:
BACKGROUND:Alzheimer's disease is thought to be caused by increased formations of neurotoxic amyloid beta (A beta) peptides, which give rise to the hallmark amyloid plaques. Therefore, pharmacological agents that reduce A beta formation may be of therapeutic benefit. OBJECTIVE:This paper reviews the pharmacology and chemical efficacy of an A beta-lowering agent, semagacestat (LY450139). METHODS:A review of the published literature pertaining to semagacestat was obtained using several electronic search engines; unpublished data on file at Eli Lilly and Co. were used as supplementary material. RESULTS/CONCLUSIONS:Semagacestat treatment lowers plasma, cerebrospinal fluid and brain A beta in a dose-dependent manner in animals and plasma and cerebrospinal fluid A beta in humans, compared with placebo-treated patients. On the basis of extant data, semagacestat seems to be well tolerated, with most adverse events related to its actions on inhibition of peripheral Notch cleavage. Thus far, clinical efficacy has not been detectable because of the short duration of the current trials. Phase III trials with 21 months of active treatment are currently underway.
journal_name
Expert Opin Pharmacotherjournal_title
Expert opinion on pharmacotherapyauthors
Henley DB,May PC,Dean RA,Siemers ERdoi
10.1517/14656560903044982subject
Has Abstractpub_date
2009-07-01 00:00:00pages
1657-64issue
10eissn
1465-6566issn
1744-7666journal_volume
10pub_type
杂志文章,评审abstract:INTRODUCTION:Following more than 20 years of Interferon (IFN)-based treatment for hepatitis C virus (HCV), the understanding of viral life cycle led to the development of new antiviral drugs directly targeting HCV replication steps. Daclatasvir (DCV) is a potent inhibitor of non-structural NS5A HCV protein with pangeno...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.2015.1109631
更新日期:2015-01-01 00:00:00
abstract::Staphylococcus aureus is a bacterial pathogen responsible for a variety of serious infections and is a frequent cause of nosocomial disease. During the last 60 years, S. aureus has developed increasing in vitro resistance to virtually all antimicrobials. In contrast, vancomycin has maintained a high degree of activity...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.8.9.1245
更新日期:2007-06-01 00:00:00
abstract:INTRODUCTION:Bipolar I disorder (BD I) is complex with a chronic course that significantly impacts a sufferer's quality of life. As of right now, there are many available treatments that aim to rapidly treat manic or depressive episodes and stabilize mood. The purpose of this report is to provide an up-to-date comprehe...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1080/14656566.2018.1426746
更新日期:2018-02-01 00:00:00
abstract:INTRODUCTION:Tubulin inhibitors including taxanes and vinca alkaloids are important components of chemotherapy regimens used in advanced non-small cell lung cancer (NSCLC). Despite a treatment paradigm shift due to molecularly-targeted therapies and immunotherapy, a majority of patients will receive chemotherapy during...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1080/14656566.2017.1316374
更新日期:2017-05-01 00:00:00
abstract::Peglyated liposomal doxorubicin was developed to maintain or enhance the demonstrated antineoplastic effects of doxorubicin, while improving the toxicity profile associated with this important cytotoxic agent. Accumulating clinical data have confirmed the activity of pegylated liposomal doxorubicin in cancers of the b...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章
doi:10.1517/14656566.7.11.1469
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND:Fampridine-SR is under submission as the first drug to be FDA approved with an indication specifically for multiple sclerosis symptoms. Compounded forms of the active agent of Fampridine-SR (4-aminopyridine) have been used in clinical practice for many years. Clinical trials have now been completed that demo...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656560903075994
更新日期:2009-08-01 00:00:00
abstract:INTRODUCTION:Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system affecting both white matter and grey matter in the earliest phases of its course. The crucial role of neurodegeneration in disability progression in MS, regardless of white matter damage, has been confirm...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1080/14656566.2018.1434143
更新日期:2018-03-01 00:00:00
abstract:INTRODUCTION:Increasing population age, obesity and physical inactivity mean that type 2 diabetes mellitus (T2DM) is increasingly common. Current treatments may be limited by adverse events, drug-drug interactions or contraindication/need for dose adjustment in patients with renal impairment. AREAS COVERED:This paper ...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.2012.642863
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:This study examined the effects of short-term administration of the sodium glucose cotransporter 2 (SGLT-2) inhibitor, dapagliflozin, on visceral fat area (VFA) in Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS:In this randomized, crossover, controlled clinical trial, overweight patient...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1080/14656566.2017.1317748
更新日期:2017-06-01 00:00:00
abstract:INTRODUCTION:Radioiodine [RAI]-resistant advanced and progressive differentiated thyroid cancer [DTC], although rare, constitutes a real challenge as its prognosis is poor and available therapeutic options, until now, have been limited. Discovery of a crucial role of distinct tyrosine kinases in DTC pathogenesis opened...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章
doi:10.1080/14656566.2016.1206078
更新日期:2016-08-01 00:00:00
abstract:INTRODUCTION:Hepatitis C virus (HCV) therapy continues to evolve rapidly. ABT-450 is a novel potent inhibitor of the non-structural 3/4A protease that has been studied in combination with several agents, allowing shorter duration of therapy and interferon-free/ribavirin-free all-oral regimens. Preliminary data from stu...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.2014.889116
更新日期:2014-04-01 00:00:00
abstract:INTRODUCTION:Postprandial hyperglycemia (PPHG) contributes to micro- and macro-vascular complications more than fasting hyperglycemia in patients with type 2 diabetes mellitus. Due to the traditional carbohydrate-rich diet, Asians, particularly Indians and Chinese need agents to control the higher risk of uncontrolled ...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.2015.1070827
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:This study investigated the safety and efficacy of metformin up-titration in Japanese patients with type 2 diabetes mellitus treated with vildagliptin (100 mg/day) and low-dose metformin (500 or 750 mg/day). RESEARCH DESIGN AND METHODS:Fifty patients were randomly allocated to the control group (maintaining...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1080/14656566.2017.1404576
更新日期:2017-12-01 00:00:00
abstract::Clopidogrel has become a mainstay in the management of acute coronary syndrome patients over the past decade, as well as an essential component of percutaneous coronary intervention (PCI) pharmacotherapy. Until recently, no prospective study has evaluated the effectiveness of clopidogrel in the setting of an ST-segmen...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.7.12.1669
更新日期:2006-08-01 00:00:00
abstract::Cervical dystonia (CD) manifests clinically through involuntary spasms of neck muscles, producing abnormal head and neck movements and postures, which is often associated with pain. CD is the most common form of focal dystonia presenting to movement disorders clinics. Chemodenervation with botulinum toxin (BTX) has be...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.2.12.1985
更新日期:2001-12-01 00:00:00
abstract:BACKGROUND:Management of a number of significant viral pathogens in transplant recipients remains challenging. OBJECTIVES:To define an optimal antiviral approach to the management of cytomegalovirus (CMV), human herpes virus-6 (HHV-6), Epstein-Barr (EBV)-associated post-transplant lymphoproliferative disorder (PTLD), ...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.9.14.2409
更新日期:2008-10-01 00:00:00
abstract::Correct education of the patient is one of the most important aspects in the treatment of Tourette's syndrome. Pharmacotherapy is often unsatisfactory and therefore should be limited to those patients who are significantly impaired. Therapy must be individualised and the most troublesome symptom should be targeted fir...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.3.7.899
更新日期:2002-07-01 00:00:00
abstract:INTRODUCTION:Graves' hyperthyroidism is associated with significant morbidity and mortality risk. The thionamides, methimazole, its pro-drug derivative carbimazole, and propylthiouracil, remain a cornerstone of management. Yet despite decades of use, optimal strategies for maximising treatment response and curtailing a...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1080/14656566.2016.1232388
更新日期:2016-10-01 00:00:00
abstract::Amifostine (Ethyoltrade mark, Alza Pharmaceuticals) is an inorganic thiophosphate cytoprotective agent known chemically as ethanethiol, 2-[3- aminopropyl)amino]dihydrogen phosphate. It is a prodrug of free thiol (WR-1065) that may act as a scavenger of free radicals generated in tissues exposed to cytotoxic drugs and ...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.2.3.479
更新日期:2001-03-01 00:00:00
abstract:BACKGROUND:Pegaptanib sodium, the first aptamer therapeutic approved for use and the first antiangiogenic agent used to treat ocular neovascular disease, acts by inhibiting the 165 isoform of vascular endothelial growth factor believed primarily responsible for pathologic ocular neovascularization and vascular permeabi...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.9.3.499
更新日期:2008-02-01 00:00:00
abstract:INTRODUCTION:Chronic constipation is a global problem affecting all ages and associated with considerable morbidity and significant financial burden for society. Though formerly defined on the basis of a single symptom, infrequent defecation; constipation is now viewed as a syndrome encompassing several complaints such...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.2016.1127356
更新日期:2016-01-01 00:00:00
abstract::Genomic variations influencing response to pharmacotherapy of pain are under investigation. Candidate genes such as (opioid)-receptors, transporters and other molecules important for pharmacotherapy are discussed. Drug metabolising enzymes represent a further major target of ongoing research in order to identify assoc...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.8.14.2235
更新日期:2007-10-01 00:00:00
abstract:INTRODUCTION:With growing knowledge of the molecular pathway of carcinogenesis, targeted therapies have become the 'blue ocean' of cancer treatment. sorafenib is an oral multikinase inhibitor that targets Raf/mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase (ERK) (Raf/MEK/ERK) and several ty...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.2012.679930
更新日期:2012-05-01 00:00:00
abstract:INTRODUCTION:Hyperphosphatemia in chronic kidney disease (CKD) is considered as an independent risk factor for surrogate clinical end points like vascular calcification (VC) and bone disease, or hard clinical outcomes like cardiovascular events. Various treatment options are available for phosphate removal or reduction...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.2015.1092521
更新日期:2015-01-01 00:00:00
abstract:INTRODUCTION:Epilepsy is a serious and common chronic neurological disease with an urgent need for novel treatment options, because 30% of all epilepsy patients do not respond to currently available drugs. Retigabine/Ezogabine (RTG) is a third-generation antiepileptic drug (AED) with a novel mechanism of action. It enh...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.2012.706278
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND:The incidence of non-melanoma skin cancer is increasing worldwide. Systemic retinoids are useful for the chemoprophylaxis of non-melanoma skin cancers. Retinoids have pleiotropic effects, but their exact cancer chemopreventive mechanism is still not clear. OBJECTIVE:The aim of this study was to review publi...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.9.8.1363
更新日期:2008-06-01 00:00:00
abstract:INTRODUCTION:Our knowledge about lower respiratory tract infections (LRTIs) has improved substantially in the last years, but the management of respiratory infections is still a challenge and we are still far from using precision medicine in their treatment. Areas covered: The approaches developed in recent years to im...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1080/14656566.2017.1328497
更新日期:2017-07-01 00:00:00
abstract:IMPORTANCE OF THE FIELD:Most guidelines suggest that failure of oral antidiabetic drugs should be followed by the addition of a basal insulin with aggressive titration of the dose. In most countries, neutral protamine Hagedorn (NPH)-insulin, glargine and detemir are the only choices. Clinical trials show that the metab...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.2010.494831
更新日期:2010-08-01 00:00:00
abstract:INTRODUCTION:Cilostazol is a reversible, selective inhibitor of PDE3A able to significantly improve walking distance in patients with intermittent claudication. However, beyond its antiplatelet and vasodilator properties, cilostazol seems to have significant effects on atherogenic dyslipidemia. AREAS COVERED:The effec...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.2011.557359
更新日期:2011-03-01 00:00:00
abstract::Osteoporosis is a severe condition, associated with significant disability as a result of fragility fractures and increased mortality. Oral bisphosphonates effectively reduce the risk of osteoporotic fracture and are generally well tolerated. Unfortunately, patient outcomes are often compromised by suboptimal therapeu...
journal_title:Expert opinion on pharmacotherapy
pub_type: 杂志文章,评审
doi:10.1517/14656566.6.13.2301
更新日期:2005-10-01 00:00:00