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Safety, pharmacokinetic and pharmacodynamic properties of single ascending dose and continuous infusion of remimazolam besylate in healthy Chinese volunteers

Abstract

Purpose

The aim of the present study was to evaluate the safety, pharmacokinetic (PK) and pharmacodynamic (PD) properties of remimazolam besylate following single ascending dose (SAD) and continuous infusion in healthy Chinese volunteers.

Methods

This was a randomized phase I study conducted in two parts. Part I was a double-blind, placebo- and midazolam-controlled, SAD study among healthy Chinese participants with a remimazolam dose of 0.025–0.4 mg/kg. Part II was an open-label, midazolam-controlled, continuous infusion study. Bispectral index (BIS) monitoring and Modified Observers Assessment of Alertness and Sedation (MOAA/S) score assessment were used to assess the PD properties.

Results

The half-life range of remimazolam was from 34.1 ± 8.1 to 59.8 ± 20.5 min in the SAD study. The sedation function was initially observed at the dose of 0.05 mg/kg remimazolam. Doses of ≥ 0.075 mg/kg exerted a peak sedation effect within 1–2 min after injection, resulting in a deeper and more rapid sedation. In the 2 h continuous infusion, remimazolam showed a deeper sedation and more rapid recovery than midazolam. For general anesthesia, an induction dosage of 0.2 mg/kg/min and a maintenance dosage of 1 mg/kg/h can achieve a satisfactory efficacy effect.

Conclusions

Remimazolam was safe and well tolerated in healthy Chinese participants. Based on the phase I clinical study, we suggest that remimazolam besylate demonstrates greater sedation and quicker recovery from sedation than midazolam.

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Acknowledgments

This study was sponsored by Yichang Humanwell Pharmaceutical Co., Ltd. We thank the contributions of WuXi AppTec Co., Ltd. for performing the concentration assays. We also thank the Department of Health Statistics, Second Military Medical University, for performing the statistical analysis.

Author information

Li-e Li, Xia Ye, Xue-yuan Yang, Xia Zhao, and Yi-min Cui designed the study. Xiao-yan Sheng, Yan Liang, Xue-yuan Yang, Xia Zhao, and Yi-min Cui conducted the clinical trial. Xue-yuan Yang is the anesthesiologist of the study, who assessed the pharmacodynamic parameters and safety of the subjects. Xiao-yan Sheng and Yan Liang analyzed the results and drafted the manuscript. Li-e Li, Xia Ye, Xia Zhao, and Yi-min Cui participated in the interpretation of results and revised the manuscript. All authors read and approved the final manuscript. The authors confirm that the PI for this paper is Yi-min Cui.

Correspondence to Yi-min Cui.

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Conflict of interest

Li-e Li and Xia Ye are employees of Yichang Humanwell Pharmaceutical Co., Ltd., which sponsored the clinical trial. The other authors have no conflicts of interest.

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Sheng, X., Liang, Y., Yang, X. et al. Safety, pharmacokinetic and pharmacodynamic properties of single ascending dose and continuous infusion of remimazolam besylate in healthy Chinese volunteers. Eur J Clin Pharmacol 76, 383–391 (2020). https://doi.org/10.1007/s00228-019-02800-3

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Keywords

  • Remimazolam besylate
  • Pharmacokinetics
  • Pharmacodynamics
  • Chinese subjects