Clinical drug investigation
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Opioids are the most powerful analgesic drugs currently available and consequently form an essential part of the treatment options for malignant and non-malignant chronic pain. However, the benefits of these medications can be offset by gastrointestinal adverse events such as nausea, vomiting and constipation, as well as adverse events affecting the CNS. These occur relatively frequently in patients receiving long-term opioids for pain relief and are a cause of additional patient suffering and reduced work and social functioning, measured as reductions in quality-of-life outcomes. ⋯ Estimated preference ratings, providing an insight into the trade-off between effective pain control and adverse events, have shown that utility decrements associated with an increase in adverse-event severity were similar in size to those caused by a shift from well controlled to poorly controlled pain. Given the rising prevalence of chronic pain conditions (affecting one in five adult Europeans), the direct and indirect costs incurred from the management of adverse events with long-term opioids are likely to be multiplied, contributing to the socioeconomic burden of chronic pain. For this reason, the adverse-event profile of opioid-based analgesics should be improved to achieve more efficient long-term pain control.
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Numerous controlled clinical trials have demonstrated the safety and efficacy of pregabalin in the treatment of neuropathic pain. The objectives of the present study were to assess the impact of pregabalin under real-world conditions on pain, pain-related sleep interference and general well-being, and to assess the tolerability and safety of pregabalin in patients diagnosed with neuropathic pain of central or peripheral origin. ⋯ Significant reductions in pain and pain-related sleep interference, combined with reductions in feelings of anxiety and depression, suggest that pregabalin under real-world conditions improves the overall health and well-being of patients with neuropathic pain.
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Comparative Study
Intra- and interindividual variabilities in the pharmacokinetics of fentanyl buccal soluble film in healthy subjects: a cross-study analysis.
Breakthrough pain describes transient exacerbations of pain that occur in cancer patients with adequately controlled background pain. Transmucosal fentanyl administration produces rapid-onset and short-duration analgesia that is effective for treating patients with breakthrough pain. Although a significant amount of research has been devoted to the study of speed of analgesia onset of transmucosal fentanyl products, few data exist on their variability in absorption, particularly within the same individual, despite the importance of this characteristic to the dose-to-dose reliability of their analgesic effect. This cross-study analysis aimed to evaluate the intra- and interindividual pharmacokinetic differences of fentanyl administered via fentanyl buccal soluble film in healthy subjects. ⋯ The minimal intraindividual variability in fentanyl absorption from the buccal soluble film demonstrates a predictable dose-to-dose exposure, which is a very desirable attribute for a medicine that is intended to treat breakthrough cancer pain, suggesting that this product would be expected to produce consistent effects in clinical practice. The greater interindividual variability highlights the need for individual titration of this product (as occurs with similar transmucosal fentanyl products), and for the availability of an adequately wide dose range.
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Sugammadex is a γ-cyclodextrin that binds with high affinity to the neuromuscular blocking agents (NMBAs) rocuronium (bromide) and vecuronium (bromide) by encapsulation. Cyclodextrins are known to form inclusion complexes with other compounds. ⋯ Of 300 drugs screened, only three (flucloxacillin, fusidic acid and toremifene) were found to have potential for a displacement interaction with sugammadex, which might potentially be noticed as a delay in recovery of the TOF ratio to 0.9. A clinical study found no evidence of a clinically relevant displacement interaction of flucloxacillin with sugammadex; these findings confirm the highly conservative nature of the modelling and simulation assumptions in the present study.
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The conventionally used dose of isotretinoin in acne causes significant dose-related adverse effects. Low-dose isotretinoin has been used successfully in mild to moderate papulopustular acne. Although isotretinoin acts against all mechanisms of acne formation, it has no significant direct antimicrobial effect. ⋯ A combination of low-dose isotretinoin and oral azithromycin pulse is effective in severe acne and has a reasonably acceptable adverse-effect profile and low post-treatment relapse rates.