Drug Des Dev Ther
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Review Comparative Study
Spotlight on ixazomib: potential in the treatment of multiple myeloma.
Despite the significant therapeutic advances achieved with proteasome inhibitors (PIs) such as bortezomib and carfilzomib in prolonging the survival of patients with multiple myeloma, the development of drug resistance, peripheral neuropathy, and pharmacokinetic limitations continue to pose major challenges when using these compounds. Ixazomib is a second-generation PI with improved activity over other PIs. Unlike bortezomib and carfilzomib, which are administered by injection, ixazomib is the first oral PI approved by US Food and Drug Administration. This review discusses the biochemical properties, mechanisms of action, preclinical efficacy, and clinical trial results leading to the US Food and Drug Administration approval of ixazomib.
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Despite declining global malaria incidence, the disease continues to be a threat to people living in endemic regions. In 2015, an estimated 214 million new malaria cases and 438,000 deaths due to malaria were recorded. Plasmodium vivax is the second most common cause of malaria next to Plasmodium falciparum. ⋯ Primaquine, the only 8-aminoquinoline derivative approved by the US Food and Drug Administration, is intended to clear intrahepatic hypnozoites of P. vivax (radical cure). However, poor adherence to a prolonged treatment course, drug-induced hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, and the emergence of resistance make it imperative to look for alternative drugs. Therefore, this review focuses on data accrued to date on tafenoquine and gives insight on the potential role of the drug in preventing relapse and radical cure of patients with vivax malaria.
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Somatostatin analogs (SSAs), which were initially used to control hormonal syndromes associated with neuroendocrine neoplasms (NENs), have been successfully proposed as antiproliferative agents, able to control tumor growth in patients affected by gastroenteropancreatic (GEP)-NENs. The development of long-acting formulations of SSAs which require only weekly or monthly injections can improve patient compliance. ⋯ Although there is no evidence of an overall survival benefit, these studies confirm the efficacy of LAN Autogel in terms of benefit in progression-free survival, and in more than half of cases, a reduction of tumor markers can be observed during treatment with this drug. Moreover, LAN Autogel is widely recognized to be effective in controlling tumor-related symptoms in the majority of patients affected by GEP tumors, especially in patients affected by carcinoid syndrome, improving considerably patients' quality of life.
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Review
Spotlight on idarucizumab and its potential for the reversal of anticoagulant effects of dabigatran.
Idarucizumab is the first targeted antidote of dabigatran, a direct oral anticoagulant used for prevention and treatment of venous thromboembolism and prevention of stroke in atrial fibrillation. Idarucizumab is a humanized fragment of a monoclonal antibody, which binds dabigatran reversibly with high affinity and, when administered intravenously, immediately neutralizes its anticoagulant effect. It is rapidly cleared by the kidney with captured dabigatran. ⋯ First, activity measurement of dabigatran in blood, useless in current practice, could be useful to guide the treatment and avoid over- or underutilization of the antidote; but so far, it has not been largely available in real time. Second, the translation of anticoagulant neutralization to an effect on mortality and better outcome is highly dependent on the global management of these patients, especially rapid diagnosis, supportive care, and easy access to antidote administration. Although idarucizumab represents a remarkable achievement in drug design and development, whether it will be an important step toward improved safety of patients treated with dabigatran in the real world will have to be demonstrated in the postmarketing phase.
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Review Meta Analysis
A quest to increase safety of anesthetics by advancements in anesthesia monitoring: scientometric analysis.
The aim of this study was to assess progress in the field of anesthesia monitoring over the past 40 years using scientometric analysis. The following scientometric indexes were used: popularity indexes (general and specific), representing the proportion of articles on either a topic relative to all articles in the field of anesthetics (general popularity index, GPI) or the subfield of anesthesia monitoring (specific popularity index, SPI); index of change (IC), representing the degree of growth in publications on a topic from one period to the next; and index of expectations (IE), representing the ratio of the number of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed. Publications on 33 anesthesia-monitoring topics were assessed. ⋯ By the 2009-2013 period, among specific monitoring topics introduced after 1980, the SPI index had a meaningful magnitude (≥1.5) in 9 of 24 topics: Bispectral Index (7.8), Transesophageal Echocardiography (4.2), Electromyography (2.8), Pulse Oximetry (2.4), Entropy (2.3), Train-of-four (2.3), Capnography (1.9), Pulse Contour (1.9), and Electrical Nerve Stimulation for neuromuscular monitoring (1.6). Only one of these topics (Pulse Contour) demonstrated (in 2009-2013) high values for both IC and IE indexes (76 and 16.9, respectively), indicating significant recent progress. We suggest that rapid growth in the field of anesthetic monitoring was one of the most important developments to compensate for the intrinsically low margins of safety of anesthetic agents.