Pharmacologic Overview of the Innovative Soft Drug Remimazolam Based on Computer Simulation. Ning Ma, Ren Guan, Xiwei Dong, Mazhong Zhang. Department of Anesthesiology & Pediatric Clinical Pharmacology Laboratory, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China Corresponding Author: Mazhong Zhang, zmzscmc@shsmu.edu.cn Abstract Objective Remimazolam is a new ultra–short-acting agent benzodiazepine for induction, maintenance of general anesthesia and procedural sedation/anesthesia. This article reviews the pharmacological characteristics, potential clinical applications and precautions based on the simulation and literatures. Methods Based on the published pharmacokinetic and/or pharmacodynamic research of remimazolam, remifentanil, midazolam, propofol and combined with real-world clinical scenarios,computer-simulated were used to obtain clinically relevant pharmacological parameters, including the onset time, peak effect time, recovery time after bolus injection. The ratio of continuous infusion/target-controlled infusion (TCI) rate of remimazolam with the same target plasma concentration. The percent context-sensitive decrement times were simulated after steady-state infusion. And also, PubMed was systematically searched for published articles in English to identified the studies of remimazolam (and CNS 7056) including pre-clinical, clinical trial and clinical application, and references were extracted if necessary. Results The onset time of remimazolam was slower than that of propofol, both had similar peak effect time and recovery time, which were much faster than midazolam. With the same target plasma concentration, the ratio of continuous infusion/TCI rate of remimazolam approaching to unity took more than 60 minutes, which was inferior to remifentanil and better than propofol, midazolam. The 50% context-sensitive decrement times (CSHT) of remimazolam was relatively constant, while propofol showed a gradual increasing, CSHTs were about 5.9 min and 13.9 min for remimazolam and propofol after 12h of steady-state infusion, respectively. Conclusions Rimimazolam is not suitable for routine use as premedication or for very short procedural sedation/anesthesia. Remimazolam has similar pharmacological characteristics to propofol for anesthesia induction and maintenance with slightly rapid recovery after discontinuation, both is suitable for administration using target-controlled infusion mode. Remimazolam has good prospects for patients’ sedation in ICU. The further studies are needed for the clinical application of remimazolam, especially drug interactions and special populations in clinical situations.