Background and Objectives Remimazolam is a new ultra-short-acting benzodiazepine currently being developed for intravenous use in procedural sedation, general anaesthesia, and intensive care unit sedation. Benzodiazepines represent a drug class associated with drug-facilitated sexual assaults, especially in combination with alcohol. Two clinical trials were designed to evaluate the oral bioavailability and pharmacokinetics/pharmacodynamics of remimazolam and to assess the potential for remimazolam misuse in drug-facilitated sexual assaults via oral ingestion. Methods Trial 1 was conducted in 14 healthy volunteers to evaluate the oral bioavailability of remimazolam. Part 1 of trial 2 was conducted in 21 healthy female volunteers to find the minimal biologically active dose of oral remimazolam. Part 2 of trial 2 was conducted in 11 healthy female volunteers to evaluate the pharmacokinetics/pharmacodynamics of oral remimazolam in combination with alcohol. Results Remimazolam undergoes rapid and extensive first-pass metabolism upon oral administration. The oral bioavailability of remimazolam was negligible (2.2% based on total systemic exposure and 1.2% based on maximum plasma concentration). Plasma clearance of both remimazolam and its metabolite was fast (elimination half-life 20‒40 min and 1.75‒2 h, respectively). Alcohol did not appear to inhibit the rapid first-pass metabolism of remimazolam. No clear sedative effects were observed for remimazolam without alcohol. Significant sedation was observed in one of ten subjects after remimazolam 360 mg (18 drug product vials) + 40% v/v alcohol. Conclusion The oral bioavailability of remimazolam is negligible, which—together with its distinct bitter taste—suggests no meaningful potential for misuse in drug-facilitated sexual assaults via oral ingestion, with or without alcohol. Clinical Trial Registration Numbers Trial 1 (NCT04113564) and trial 2 (NCT04113343) both retrospectively registered on 2 October 2019. Electronic supplementary material The online version of this article (10.1007/s40268-020-00317-0) contains supplementary material, which is available to authorized users.

PurposeAcute pharyngitis is an uncomfortable disorder mostly caused by viruses and for which antibiotics are unwarranted. This study compared lozenges containing ectoine, a natural extremolyte, with hyaluronic acid lozenges and hypertonic saline gargle for symptomatic treatment of acute viral pharyngitis.MethodsThis prospective, controlled clinical study, recruited 90 patients with moderate-to-severe pharyngitis symptoms who chose to use either ectoine (n = 35), hyaluronic acid (n = 35), or saline gargle (n = 20). Patients applied their 7-day treatment from the inclusion visit (V1) until the end-of-study visit (V2). Patients’ pharyngitis symptoms, general health, general treatment effectiveness and tolerability, and patient compliance were assessed by investigators and patients.ResultsThe sum score for three primary symptoms (pain on swallowing, urge to cough, and hoarseness) decreased by 79.5% (ectoine), 72.2% (hyaluronic acid), and 44.8% (saline gargle). Both lozenges were significantly superior to saline gargle (P < 0.05). Regarding general health improvement, ectoine was significantly superior to saline gargle (72.5% vs. 45.2%, P < 0.05), but hyaluronic acid (63.3%) was not. At V2, 65.7% of patients receiving ectoine reported “very good” general health vs. 48.6% of those receiving hyaluronic acid and 20.0% using saline gargle. Ectoine was significantly superior (P < 0.05) to both hyaluronic acid and saline gargle in terms of tolerability and patient compliance. No patients taking ectoine reported unpleasant sensations while applying their treatment, whereas almost half of patients using hyaluronic acid lozenges and saline gargle did.ConclusionTreatment with ectoine lozenges significantly relieves moderate-to-severe symptoms of acute viral pharyngitis and is more effective and tolerable than treatments with hyaluronic acid lozenges and hypertonic saline gargle.Electronic supplementary materialThe online version of this article (10.1007/s00405-019-05324-9) contains supplementary material, which is available to authorized users.

Purpose. This study investigated an inhalation solution containing ectoine, a bacterial-derived extremolyte, for the treatment of acute bronchitis and acute respiratory infections in comparison with saline inhalation solution. Methods. This prospective, controlled, observational study comprised an inclusion visit (day 1), a final visit (day 7), and a follow-up questionnaire (day 17). The treatment itself was administered from day 1 to day 7. The Bronchitis Severity Score, patients’ general health, general effectiveness of the treatment, tolerability, and adverse events were compared between two groups. Results. In total, 135 patients were recruited; 79 patients received ectoine inhalation solution and 56 saline inhalation solution. After treatment, symptom scores decreased significantly in both groups (P < 0.05); the reduction in symptom scores was slightly greater in the ectoine group than in the saline group. The first significant reduction in symptom scores (P < 0.05) occurred earlier in the ectoine group than in the saline group. The differences in the area under the curve for the symptoms of dyspnea and auscultation findings were significant in favor of ectoine (P < 0.05). After treatment, more patients and physicians in the ectoine group assessed their or their patients’ condition as “completely recovered” or “greatly improved” than those in the saline group. Almost all patients and physicians assessed the tolerability of both treatments as “good” or “very good”. Conclusions. Ectoine inhalation solution seems to be slightly more effective than saline inhalation solution for the treatment of acute bronchitis and acute respiratory infections.

Although muscle development has been widely studied in Drosophila melanogaster there are still many gaps in our knowledge, and it is not known to which extent this knowledge can be transferred to other arthropods. To help closing these gaps we participated in a large-scale RNAi screen that used the red flour beetle, Tribolium castaneum, as a screening platform. The effects of systemic RNAi were screened upon double-stranded RNA injections into appropriate muscle-GFP tester strains.Injections into larvae were followed by the analysis of the adult thoracic muscle patterns, and injections into pupae by the analysis of the late embryonic/larval muscle patterns. Herein we focus on the results of our pupal injection screen for late embryonic/larval muscle phenotypes, which covered 8.500 of a total of ~16.500 genes of the Tribolium genome. Apart from many genes known from Drosophila as regulators of muscle development, a collection of genes previously unconnected to muscle development yielded larval body wall and leg muscle phenotypes. We present the main candidates that remained after being processed through a series of verification and selection steps. Further, we discuss why distinct though overlapping sets of genes are revealed by the Drosophila and Tribolium screening approaches.

No abstract