Drugs in R&D
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Randomized Controlled Trial Multicenter Study Comparative Study
Longitudinal Assessment of the Effect of Atrasentan on Thoracic Bioimpedance in Diabetic Nephropathy: A Randomized, Double-Blind, Placebo-Controlled Trial.
Fluid retention is a common adverse event in patients who receive endothelin (ET) receptor antagonist therapy, including the highly selective ETA receptor antagonist, atrasentan. ⋯ We conclude that thoracic bioimpedance did not reflect changes in weight gain or edema with atrasentan treatment in this study. However, the sample size was small, and it may be of interest to explore the use of thoracic bioimpedance in a larger population to understand its potential clinical use in monitoring fluid retention in patients with chronic kidney disease who receive ET receptor antagonists.
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Eslicarbazepine acetate is a new anti-epileptic drug belonging to the dibenzazepine carboxamide family that is currently approved as adjunctive therapy and monotherapy for partial-onset (focal) seizures. The drug enhances slow inactivation of voltage-gated sodium channels and subsequently reduces the activity of rapidly firing neurons. Eslicarbazepine acetate has few, but some, drug-drug interactions. ⋯ The drug is generally well tolerated, and the most common side effects include dizziness, headache, and diplopia. One of the greatest strengths of eslicarbazepine acetate is its ability to be administered only once per day. Eslicarbazepine acetate has many advantages over older anti-epileptic drugs, and it should be strongly considered when treating patients with partial-onset epilepsy.
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Risk Evaluation and Mitigation Strategies (REMSs) with Elements to Assure Safe Use (ETASU) are requested for drugs with significant safety risks. We reviewed REMS programs issued since 2011 to evaluate their rationales, characteristics, and consistencies, and evaluated their impact on improving drug safety. We conducted a literature search and a survey of relevant websites (FDA, manufacturers, and REMSs). ⋯ REMSs with ETASU continue to be implemented but their impact on improving drug safety is still not documented. Hence, one of the main requirements of the FDA Amendments Act of 2007 is not being addressed. In addition, REMSs are complex and their logic is inconsistent; we recommend a thorough re-evaluation of the REMS program.
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For most physicians, quantification of drug-specific immunoglobulin E (drug-sIgE) antibodies constitutes the primary in vitro measure to document immediate drug hypersensitivity reactions (IDHR). Unfortunately, this is often insufficient to correctly identify patients with IgE-mediated IDHR and impossible for non-IgE-mediated IDHR that result from alternative routes of basophil and mast cell activation. In these difficult cases, diagnosis might benefit from cellular tests such as basophil activation tests (BAT). ⋯ Although drug-sIgE assays and BAT can provide useful information in the diagnosis of IDHR, their predictive value is not absolute. Large-scale collaborative studies are mandatory to harmonize and optimize test protocols and to establish drug-specific decision thresholds.
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Comparative Study
Cytotoxicity of Oxycodone and Morphine in Human Neuroblastoma and Mouse Motoneuronal Cells: A Comparative Approach.
Oxycodone is the mo st commonly used opioid for the treatment of moderate to severe pain. The peak cerebrospinal fluid concentration after epidural oxycodone was reported to be 300-fold greater (0.025 mM) than when administered intravenously after gynecologic surgery. Additionally, those patients administered epidural oxycodone had lower pain scores, needed less rescue analgesics and had fewer adverse effects compared with intravenous administration. However, oxycodone neurotoxicity requires evaluation before intrathecal implementation for routine clinical use. ⋯ Based on these results, it seems that the cytotoxicity of oxycodone in motoneuronal cells is similar to or less than that of morphine, and occurs only at concentrations above the peak clinical concentration in the cerebrospinal fluid after epidural administration.