Pharmacokinetic Properties and Therapeutic Effectiveness of Remimazolam in ICU Patients With Mechanical Ventilation: A Preliminary Study.

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 (R = 0.36, p = 0.00013) and clearance (R = 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.