Pharmacokinetic Properties and Therapeutic Effectiveness of Remimazolam in ICU Patients With Mechanical Ventilation: A Preliminary Study
ABSTRACT The pharmacokinetic (PK) profile of remimazolam, a ultra‐short‐acting benzodiazepine, has been investigated for procedural sedation and anesthesia, but its pharmacokinetics, pharmacodynamics, and optimal dosing for ICU sedation are still unclear. This prospective, single‐center, double‐blin...
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| Format: | Article |
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Wiley
2025-06-01
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| Series: | Pharmacology Research & Perspectives |
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| Online Access: | https://doi.org/10.1002/prp2.70130 |
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| author | Jing Hu Yuhan Zhao Litao Shao Wenhui Zhang Han Wang Yun Liu Mengxiang Su Xiangrong Zuo |
| author_facet | Jing Hu Yuhan Zhao Litao Shao Wenhui Zhang Han Wang Yun Liu Mengxiang Su Xiangrong Zuo |
| author_sort | Jing Hu |
| collection | DOAJ |
| description | ABSTRACT The pharmacokinetic (PK) profile of remimazolam, a ultra‐short‐acting benzodiazepine, has been investigated for procedural sedation and anesthesia, but its pharmacokinetics, pharmacodynamics, and optimal dosing for ICU sedation are still unclear. This prospective, single‐center, double‐blind randomized controlled trial studied ICU adults on mechanical ventilation for over 24 h. Participants were divided into three groups, each receiving a 0.2 mg/kg remimazolam loading dose in less than a minute, followed by maintenance doses of 0.1, 0.3, or 0.5 mg/kg/h. Plasma concentrations of remimazolam and its metabolites were measured using UPLC‐MS/MS, and pharmacokinetic parameters were calculated using one‐compartmental methods with WinNolin. The study also assessed pharmacodynamic indicators (RASS score) and the impact of the clinical indicators on pharmacokinetic parameters. The study on 36 ICU patents using a one‐compartment model found that after 24 h of continuous intravenous remimazolam infusion, the drug had a median clearance rate of 22.23 mL/kg/min and a volume of distribution of 2656.58 mL/kg. The half‐life was 101.791 min in ventilated patients, while its metabolites had a slower clearance rate of 0.49 mL/kg/min and an longer half‐life of 656.02 min. Sedation levels were mild to moderate at dosed of 0.1–0.3 mg/kg/h. Liver function significantly affected remimazolam metabolism, influencing the half‐life (R2 = 0.36, p = 0.00013) and clearance (R2 = 0.13, p = 0.04). The pharmacokinetic study indicates that remimazolam is effective and safe for ICU patients on mechanical ventilation, with a 24‐h infusion demonstrating rapid clarence and a clear dose‐effect relationship. It provides mild to moderate sedation at 0.1–0.3 mg/kg/h, but caution is advised for patients with severe liver dysfunction due to its impact on drug metabolism. Trial Registration: ClinicalTrials.gov identifier: NCT05480787 |
| format | Article |
| id | doaj-art-4ed6d92e84aa41a099ded470332f8a53 |
| institution | Kabale University |
| issn | 2052-1707 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj-art-4ed6d92e84aa41a099ded470332f8a532025-08-20T03:45:40ZengWileyPharmacology Research & Perspectives2052-17072025-06-01133n/an/a10.1002/prp2.70130Pharmacokinetic Properties and Therapeutic Effectiveness of Remimazolam in ICU Patients With Mechanical Ventilation: A Preliminary StudyJing Hu0Yuhan Zhao1Litao Shao2Wenhui Zhang3Han Wang4Yun Liu5Mengxiang Su6Xiangrong Zuo7Department of Pharmacy The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu People's Republic of ChinaDepartment of Critical Care Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu People's Republic of ChinaSchool of Pharmacy, China Pharmaceutical University Nanjing ChinaDepartment of Critical Care Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu People's Republic of ChinaDepartment of Critical Care Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu People's Republic of ChinaDepartment of Critical Care Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu People's Republic of ChinaChina National Narcotics Control Commission‐China Pharmaceutical University Joint Laboratory on Key Technologies of Narcotics Control Nanjing ChinaDepartment of Critical Care Medicine The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu People's Republic of ChinaABSTRACT The pharmacokinetic (PK) profile of remimazolam, a ultra‐short‐acting benzodiazepine, has been investigated for procedural sedation and anesthesia, but its pharmacokinetics, pharmacodynamics, and optimal dosing for ICU sedation are still unclear. This prospective, single‐center, double‐blind randomized controlled trial studied ICU adults on mechanical ventilation for over 24 h. Participants were divided into three groups, each receiving a 0.2 mg/kg remimazolam loading dose in less than a minute, followed by maintenance doses of 0.1, 0.3, or 0.5 mg/kg/h. Plasma concentrations of remimazolam and its metabolites were measured using UPLC‐MS/MS, and pharmacokinetic parameters were calculated using one‐compartmental methods with WinNolin. The study also assessed pharmacodynamic indicators (RASS score) and the impact of the clinical indicators on pharmacokinetic parameters. The study on 36 ICU patents using a one‐compartment model found that after 24 h of continuous intravenous remimazolam infusion, the drug had a median clearance rate of 22.23 mL/kg/min and a volume of distribution of 2656.58 mL/kg. The half‐life was 101.791 min in ventilated patients, while its metabolites had a slower clearance rate of 0.49 mL/kg/min and an longer half‐life of 656.02 min. Sedation levels were mild to moderate at dosed of 0.1–0.3 mg/kg/h. Liver function significantly affected remimazolam metabolism, influencing the half‐life (R2 = 0.36, p = 0.00013) and clearance (R2 = 0.13, p = 0.04). The pharmacokinetic study indicates that remimazolam is effective and safe for ICU patients on mechanical ventilation, with a 24‐h infusion demonstrating rapid clarence and a clear dose‐effect relationship. It provides mild to moderate sedation at 0.1–0.3 mg/kg/h, but caution is advised for patients with severe liver dysfunction due to its impact on drug metabolism. Trial Registration: ClinicalTrials.gov identifier: NCT05480787https://doi.org/10.1002/prp2.70130intensive caremechanical ventilationpharmacokineticsremimazolamsedation |
| spellingShingle | Jing Hu Yuhan Zhao Litao Shao Wenhui Zhang Han Wang Yun Liu Mengxiang Su Xiangrong Zuo Pharmacokinetic Properties and Therapeutic Effectiveness of Remimazolam in ICU Patients With Mechanical Ventilation: A Preliminary Study Pharmacology Research & Perspectives intensive care mechanical ventilation pharmacokinetics remimazolam sedation |
| title | Pharmacokinetic Properties and Therapeutic Effectiveness of Remimazolam in ICU Patients With Mechanical Ventilation: A Preliminary Study |
| title_full | Pharmacokinetic Properties and Therapeutic Effectiveness of Remimazolam in ICU Patients With Mechanical Ventilation: A Preliminary Study |
| title_fullStr | Pharmacokinetic Properties and Therapeutic Effectiveness of Remimazolam in ICU Patients With Mechanical Ventilation: A Preliminary Study |
| title_full_unstemmed | Pharmacokinetic Properties and Therapeutic Effectiveness of Remimazolam in ICU Patients With Mechanical Ventilation: A Preliminary Study |
| title_short | Pharmacokinetic Properties and Therapeutic Effectiveness of Remimazolam in ICU Patients With Mechanical Ventilation: A Preliminary Study |
| title_sort | pharmacokinetic properties and therapeutic effectiveness of remimazolam in icu patients with mechanical ventilation a preliminary study |
| topic | intensive care mechanical ventilation pharmacokinetics remimazolam sedation |
| url | https://doi.org/10.1002/prp2.70130 |
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