Research progress in Remimazolam Besylate

doi:10.3877/cma.j.issn.2096-1537.2024.04.013

Abstract

Abstract:

Remimazolam Besylate is a novel, ultra-short-acting Benzodiazepine which rapidly hydrolyzed into an inactive carboxylic acid metabolite by non-specific tissue esterase.It has characteristics of fast onset, quick recovery, and predictable duration of action.Its sedative effect can be antagonized by Flumazenil.Prolonged infusion of Remimazolam besylate is unlikely to result in accumulation.Remimazolam Besylate has been currently approved for procedural sedation, induction and maintenance of general anesthesia in several countries.Preliminary studies have shown certain advantages in critically ill patients sedation.In this study, mechanisms, pharmacokinetics, clinical applications, adverse events and application prospects of Remimazolam besylate are reviewed to provide evidence for its development, research and application.

Key words: Remimazolam, Sedation, Intensive care

Yun Tang, Xiaobo Yang, Yuan Yu, Huaqing Shu, You Shang. Research progress in Remimazolam Besylate[J]. Chinese Journal of Critical Care & Intensive Care Medicine(Electronic Edition), 2024, 10(04): 389-393.

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References 37

1	Kam PC, Cardone D.Propofol infusion syndrome [J].Anaesthesia,2007, 62(7): 690-701.
2	Mandema JW, Tuk B, van Steveninck AL, et al.Pharmacokineticpharmacodynamic modeling of the central nervous system effects of Midazolam and its main metabolite alpha-hydroxymidazolam in healthy volunteers [J].Clin Pharmacol Ther, 1992, 51(6): 715-728.
3	Lee A, Shirley M.Remimazolam: a review in procedural sedation [J].Drugs, 2021, 81(10): 1193-1201.
4	Sneyd JR, Gambus PL, Rigby-Jones AE.Current status of perioperative hypnotics, role of Benzodiazepines, and the case for Remimazolam: a narrative review [J].Br J Anaesth, 2021, 127(1): 41-55.
5	Kilpatrick GJ.Remimazolam: non-clinical and clinical profile of a new sedative/anesthetic agent [J].Front Pharmacol, 2021, 12: 690875.
6	Birgenheier NM, Stuart AR, Egan TD.Soft drugs in anesthesia:remifentanil as prototype to modern anesthetic drug development [J].Curr Opin Anaesthesiol, 2020, 33(4): 499-505.
7	Kilpatrick GJ, McIntyre MS, Cox RF, et al.CNS 7056: a novel ultrashort-acting Benzodiazepine [J].Anesthesiology, 2007, 107(1): 60-66.
8	Sigel E, Ernst M.The Benzodiazepine binding sites of GABA(A)receptors [J].Trends Pharmacol Sci, 2018, 39(7): 659-671.
9	Antonik LJ, Goldwater DR, Kilpatrick GJ, et al.A placebo- and Midazolam-controlled phase Ⅰ single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of Remimazolam(CNS 7056): Part Ⅰ.Safety, efficacy, and basic pharmacokinetics [J].Anesth Analg, 2012, 115(2): 274-283.
10	Wiltshire HR, Kilpatrick GJ, Tilbrook GS, et al.A placeboand Midazolam-controlled phase Ⅰ single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of Remimazolam (CNS 7056): Part Ⅱ.Population pharmacokinetic and pharmacodynamic modeling and simulation [J].Anesth Analg, 2012,115(2): 284-296.
11	Schüttler J, Eisenried A, Lerch M, et al.Pharmacokinetics and pharmacodynamics of Remimazolam (CNS 7056) after continuous infusion in healthy male volunteers: partⅠ.pharmacokinetics and clinical pharmacodynamics [J].Anesthesiology, 2020, 132(4): 636-651.
12	Sheng XY, Liang Y, Yang XY, et al.Safety, pharmacokinetic and pharmacodynamic properties of single ascending dose and continuous infusion of Remimazolam besylate in healthy Chinese volunteers [J].Eur J Clin Pharmacol, 2020, 76(3): 383-391.
13	Pesic M, Stöhr T, Ossig J, et al.Remimazolam has low oral bioavailability and no potential for misuse in drug-facilitated sexual assaults, with or without alcohol: results from two randomised clinical trials [J].Drugs R D, 2020, 20(3): 267-277.
14	Pesic M, Schippers F, Saunders R, et al.Pharmacokinetics and pharmacodynamics of intranasal Remimazolam-a randomized controlled clinical trial [J].Eur J Clin Pharmacol, 2020, 76(11): 1505-1516.
15	Stöhr T, Colin PJ, Ossig J, et al.Pharmacokinetic properties of Remimazolam in subjects with hepatic or renal impairment [J].Br J Anaesth, 2021, 127(3): 415-423.
16	Lohmer LL, Schippers F, Petersen KU, et al.Time-to-event modeling for Remimazolam for the indication of induction and maintenance of general anesthesia [J].J Clin Pharmacol, 2020, 60(4): 505-514.
17	Worthington MT, Antonik LJ, Goldwater DR, et al.A phase Ⅰ b, dosefinding study of multiple doses of Remimazolam (CNS 7056) in volunteers undergoing colonoscopy [J].Anesth Analg, 2013, 117(5):1093-1100.
18	Kleiman RB, Darpo B, Thorn M, et al.Potential strategy for assessing QT/QTc interval for drugs that produce rapid changes in heart rate: Electrocardiographic assessment of the effects of intravenous Remimazolam on cardiac repolarization [J].Br J Clin Pharmacol,2020, 86(8): 1600-1609.
19	Eisenried A, Schüttler J, Lerch M, et al.Pharmacokinetics and pharmacodynamics of Remimazolam (CNS 7056) after continuous infusion in healthy male volunteers: part Ⅱ.pharmacodynamics of electroencephalogram effects [J].Anesthesiology, 2020, 132(4): 652-666.
20	Borkett KM, Riff DS, Schwartz HI, et al.A Phase Ⅱa, randomized,double-blind study of Remimazolam (CNS 7056) versus Midazolam for sedation in upper gastrointestinal endoscopy [J].Anesth Analg,2015, 120(4): 771-780.
21	Pambianco DJ, Borkett KM, Riff DS, et al.A phase Ⅱb study comparing the safety and efficacy of Remimazolam and Midazolam in patients undergoing colonoscopy [J].Gastrointest Endosc, 2016, 83(5):984-992.
22	Rex DK, Bhandari R, Desta T, et al.A phase Ⅲ study evaluating the efficacy and safety of Remimazolam (CNS 7056) compared with placebo and Midazolam in patients undergoing colonoscopy [J].Gastrointest Endosc, 2018, 88(3): 427-437.e426.
23	Rex DK, Bhandari R, Lorch DG, et al.Safety and efficacy of Remimazolam in high risk colonoscopy: a randomized trial [J].Dig Liver Dis, 2021, 53(1): 94-101.
24	Pastis NJ, Yarmus LB, Schippers F, et al.Safety and efficacy of Remimazolam compared with Placebo and Midazolam for moderate sedation during bronchoscopy [J].Chest, 2019, 155(1): 137-146.
25	Zhou YY, Yang ST, Duan KM, et al.Efficacy and safety of Remimazolam besylate in bronchoscopy for adults: a multicenter,randomized, double-blind, positive-controlled clinical study [J].Front Pharmacol, 2022, 13: 1005367.
26	Zhang X, Li S, Liu J.Efficacy and safety of Remimazolam besylate versus Propofol during hysteroscopy: single-centre randomized controlled trial [J].BMC Anesthesiol, 2021, 21(1): 156.
27	Doi M, Morita K, Takeda J, et al.Efficacy and safety of Remimazolam versus Propofol for general anesthesia: a multicenter, single-blind,randomized, parallel-group, phase Ⅱb/ Ⅲ trial [J].J Anesth, 2020,34(4): 543-553.
28	Doi M, Hirata N, Suzuki T, et al.Safety and efficacy of Remimazolam in induction and maintenance of general anesthesia in high-risk surgical patients (ASA class Ⅲ): results of a multicenter, randomized,double-blind, parallel-group comparative trial [J].J Anesth, 2020,34(4): 491-501.
29	Freyer N, Knöspel F, Damm G, et al.Metabolism of Remimazolam in primary human hepatocytes during continuous long-term infusion in a 3-D bioreactor system [J].Drug Des Devel Ther, 2019, 13: 1033-1047.
30	Tang Y, Yang X, Shu H, et al.Remimazolam besylate for sedation of postoperative patients in intensive care units: a phase Ⅰ, open label,dose-finding study [J].Chin Med J (Engl), 2022, 135(17): 2134-2136.
31	Tang Y, Yang X, Yu Y, et al.Remimazolam besylate versus Propofol for long-term sedation during invasive mechanical ventilation: a pilot study [J].Crit Care, 2022, 26(1): 279.
32	Tang Y, Gao X, Xu J, et al.Remimazolam besylate versus Propofol for deep sedation in critically ill patients: a randomized pilot study [J].Crit Care, 2023, 27(1):474.
33	Tsurumi K, Takahashi S, Hiramoto Y, et al.Remimazolam anaphylaxis during anesthesia induction [J].J Anesth, 2021, 35(4): 571-575.
34	Sasaki H, Hoshijima H, Mizuta K.Ringer’s acetate solution-induced precipitation of Remimazolam [J].Br J Anaesth, 2021, 126(3):e87-e89.
35	Yoshida K, Tanaka S, Watanabe K.A case of intravenous line occlusion when using Acetated Ringer’s solution and Remimazolam[J].J Clin Anesth, 2021, 70: 110190.
36	Uchida S, Takekawa D, Hashiba E, et al.Anesthetic management with Remimazolam in a patient with Child-Pugh C liver cirrhosis: a case report [J].JA Clin Rep, 2022, 8(1): 99.
37	Schippers F, Pesic M, Saunders R, et al.Randomized crossover trial to compare abuse liability of intravenous Remimazolam versus intravenous Midazolam and placebo in recreational central nervous system depressant users [J].J Clin Pharmacol, 2020, 60(9): 1189-1197.

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