Drug news & perspectives最新文献

Susceptibility testing of fungi and development of interpretative breakpoints has become increasingly important due to the growing incidence of invasive fungal infections, the number and classes of antifungals, and the emerging reports of acquired resistance. The subcommittee on antifungal susceptibility testing of the European Committee on Antibiotic Susceptibility Testing (EUCAST) has developed standards for susceptibility testing of fermentative yeasts and molds as well as proposing breakpoints for fluconazole and voriconazole against Candida. The aim of this work is to describe the EUCAST process of setting breakpoints for antifungals. Five aspects are evaluated during the process of developing breakpoints: 1) the most common dosage used in each European country, 2) the definition of the wild-type population for each target microorganism at the species level and the determination of epidemiological cutoffs, 3) the drug's pharmacokinetics and 4) pharmacodynamics, including Monte Carlo simulations, and 5) the correlation of MICs with clinical outcome of patients treated with the compound. When insufficient data are available (e.g., due to lack of information on the clinical outcome of infections caused by isolates with an elevated MIC), epidemiological cutoff values, rather than breakpoints, are recommended until the necessary information becomes available.

Chronic inflammation is increasingly regarded not just as a consequence of a continuous infectious hazard, but also as an integral part of many noninfectious diseases such as autoimmune disorders, diabetes or cardiovascular disease. Thus, it is not surprising that some hormonal systems, like the renin-angiotensin system (RAS), which were originally described in the context of cardiovascular disease have also turned out to be major regulators of the inflammatory response. This review focuses on the role of the RAS in inflammation, with particular emphasis on the role of the angiotensin AT(2) receptor. While the proinflammatory features of the angiotensin AT(1) receptor are well established, most current evidence supports an anti-inflammatory role for AT(2) receptor. However, data on this receptor in inflammation are still rather sparse and are somewhat controversial. This article will discuss the principal mechanisms of AT(2) receptor-coupled interference with proinflammatory pathways as well as data derived from animal models of specific diseases. Finally, it will give a brief outlook into new possibilities in AT(2) receptor research and in the potential utilization of AT(2) receptor stimulation as a novel pharmacological concept in anti-inflammation.

In this white paper, Thomson Reuters provides a snapshot of the imaging biomarkers at use in research and development, and the clinic; examines key technical and commercialization challenges; and identifies promising avenues for progress in the field with insight from experts from industry and academia.

Angiogenesis is crucial for the growth of cancer. As such, it has become an established target to fight cancer. Metronomic chemotherapy-the chronic administration of chemotherapy at relatively low, minimally toxic doses on a frequent schedule of administration, at close regular intervals, with no prolonged drug-free breaks-is a potential approach to control advanced cancer disease. It is thought to work primarily through antiangiogenic mechanisms and has the property to kill resistant cancer cells and/or to inhibit tumor growth while significantly reducing undesirable toxic side effects. Here, we will discuss potential mechanisms of action of metronomic chemotherapy and briefly review the data regarding the clinical experience with this kind of anticancer treatment. Based on recent insights in the various mechanisms of action, we will try to predict the potential new developments of metronomic chemotherapy in oncology.

Epidemiological studies have begun to suggest obesity is a risk factor for chronic migraine, although no causal relationship has been established and risk factors for progression from episodic to chronic migraine remain unknown. The neuropeptide calcitonin gene-related peptide (CGRP) plays a important role in the pathophysiology of migraine. Here, the potential role of CGRP as a molecular link between obesity and migraine is reviewed. A mechanistic association is supported by several lines of evidence: 1) common markers are elevated in obesity and migraine, 2) adipose tissue secretes proinflammatory cytokines and adipocytokines that have been implicated in migraine pathophysiology and 3) elevated levels of CGRP have been found in plasma of obese individuals. We propose that CGRP released from trigeminal neurons may represent a biological link between obesity and migraine. Enhanced trigeminal CGRP production in obese susceptible individuals may lower the threshold necessary to trigger migraine attacks, leading to more frequent episodes and eventually to chronic migraine.

The integration of diagnostics into the selection, administration, dosing and monitoring of the use of anticancer drugs has continued to impact the pharmaceutical industry with particular emphasis on cancers of the breast, colon and lung. An update is given on the biomarkers for these cancers.

Regulatory agencies are the gateway between the pharma/biotech industry and patients and can serve as stimulators of new drug development. This article highlights several means of doing so implemented thus far, many with already impressive histories, such as orphan drug legislation, and others of a more experimental nature, such as the FDA's priority review voucher program. These initiatives represent different approaches to finding treatments for rare and widespread but neglected diseases, as well as speeding the development process for pharmaceutical and biological agents more generally. Commercial incentives, streamlined regulatory processing, exploratory trial designs, research assistance and cash infusions are all means of promoting drug development being explored in the United States, Europe and beyond. In some cases, such as fast track designation and priority review vouchers, regulatory agencies have turned their own processes into incentives, offering advantageous alternative routes to product approval, like a faster lane on the highway for vehicles carrying multiple passengers. In 2009, regulatory agencies and the governments they represent also had to confront two tremendous challenges: the global recession and the H1N1 influenza virus pandemic. These tests have been met with increased funding in the former case and coordinated efforts to develop, approve and stockpile H1N1 vaccines in the latter.

This annual article presents new drugs and biologics that were launched or approved for the first time during the previous year. In 2009, 51 new medicines and vaccines reached their first markets. Line extensions (new indications, new formulations and new combinations of previously marketed products) accounted for more than 30% of the new products launched in 2009. In addition to providing an overview of all drugs and biologics launched or approved for the first time ever in the previous year, this article will also review in further depth the first-in-class drugs launched for the first time last year, providing a better understanding of their novel mechanisms of action; an analysis of the discovery and development periods for the year's new products; and a comprehensive overview of drug repositioning as a strategy for extending the life spans of medicines. We also provide a brief glimpse at selected drugs and biologics which could reach their first markets in the foreseeable future.

The research-based biopharmaceutical industry faced new challenges during 2009, many rooted in the global economic recession, which further complicated a situation that was already characterized by the obstacles traditionally debated in this and other publications: generic competition, patent expirations and accusations of declining innovation. Once again, companies have been forced to seek out new strategies (mergers, acquisitions, licensing deals, offshore clinical testing and more) in order to cut costs and fill the gaps in their R&D pipelines. However, it is conceivable that the existing R&D model has limitations that can no longer be overcome via these traditional strategies and that the time has come for an entirely new model.