Bosentan is an orally bioavailable, well-tolerated, and active ET-1 antagonist with a low clearance and a moderate volume of distribution. Its intravenous use is limited because of local intolerability.

Single-dose administration of sugammadex 16, 20, or 32 mg kg(-1) in combination with rocuronium 1.2 mg kg(-1) or vecuronium 0.1 mg kg(-1) was well tolerated with no clinical evidence of residual neuromuscular block, confirming that these combinations can safely be administered simultaneously to non-anaesthetized subjects. Rocuronium and vecuronium plasma concentrations decreased faster than those of sugammadex, reducing the theoretical risk of neuromuscular block developing over time.

Rapid re-onset of NMB occurred after repeat dose of rocuronium 1.2 mg kg(-1) as early as 5 min after sugammadex in healthy volunteers. Re-onset of block took longer if second rocuronium dose was <25 min after sugammadex. The duration of action of second rocuronium dose increased with later repeat dose time points.

IntroductionEsmirtazapine is evaluated as a novel drug for treatment of insomnia.PurposeThe present study was designed to assess residual effects of single and repeated doses of esmirtazapine 1.5 and 4.5 mg on actual driving in 32 healthy volunteers in a double-blind, placebo-controlled study. Treatment with single doses of zopiclone 7.5 mg was included as active control.MethodsTreatments were administered in the evening. Driving performance was assessed in the morning, 11 h after drug intake, in a standardized on-the-road highway driving test. The primary study parameter was standard deviation of lateral position (SDLP), a measure of “weaving”. All subjects were subjected to CYP2D6 phenotyping in order to distinguish poor metabolizers from extensive metabolizers of esmirtazapine.ResultsOverall, esmirtazapine 1.5 mg did not produce any clinically relevant change in SDLP after single and repeated dosing. Driving impairment, i.e., a rise in SDLP, did occur after a single-dose administration of esmirtazapine 4.5 mg but was resolved after repeated doses. Acute driving impairment was more pronounced after both doses of esmirtazapine in a select group of poor metabolizers (N = 7). A single-dose zopiclone 7.5 mg also increased SDLP as expected.ConclusionIt is concluded that single and repeated doses of 1.5 mg esmirtazapine are generally not associated with residual impairment. Single-dose administration of 4.5 mg esmirtazapine was associated with residual impairment that generally resolved after repeated administration. Exploratory analysis in a small group of poor CYP 2D6 metabolizers suggested that these subjects are more sensitive to the impairing effects of esmirtazapine on car driving.

http://www.clinicaltrials.gov NCT00988065; Protocol number P06042.