Prolonged infusion of remimazolam in surgical and medical intensive care unit patients: a pilot pharmacokinetic study

TL;DR

This study examines how remimazolam behaves in the blood of ICU patients receiving long-term infusions, finding stable levels without significant accumulation.

Contribution

The study provides new pharmacokinetic data for prolonged remimazolam infusion in surgical and medical ICU patients.

Findings

Steady-state plasma concentrations showed modest intrasubject and moderate intersubject variability.

No statistically significant differences in clearance or volume of distribution between surgical and medical ICU groups.

No evidence of time-dependent accumulation of remimazolam in either group.

Abstract

The pharmacokinetics of prolonged remimazolam infusion in patients undergoing long-term mechanical ventilation remain unclear. This study aimed to evaluate the pharmacokinetics of remimazolam administered continuously for 24 h.

This open-label pharmacokinetic analysis enrolled patients requiring mechanical ventilation into two groups: the surgical group, which received remimazolam during and after surgery, and the medical ICU group, which received remimazolam in the intensive care unit (ICU). Remimazolam was administered at a fixed rate of 0.1 mg/kg/h for ≥ 24 h, and blood samples were collected at regular intervals. Plasma remimazolam concentrations were measured by tandem mass spectrometry.

Twenty patients (10 in each group) completed the study. The median duration of remimazolam infusion was 24.0 h in the surgical group and 102.0 h in the medical ICU group. The steady-state plasma concentrations in both the surgical and medical ICU groups exhibited modest intrasubject variability (4.46–32.73%) and moderate intersubject variability (16.45–31.71%), with all values falling within clinically acceptable intermediate ranges. The plasma remimazolam concentration at the end of infusion was 130.7 ng/mL (95% confidence interval [CI] 115.2–146.1) in the surgical group and 134.3 ng/mL (95% CI 98.7–170.0) in the medical ICU group. Noncompartmental analysis showed that the clearance was 54.3 L/h (95% CI 47.6–61.8) and 55.6 L/h (95% CI 42.8–72.1) (P = 0.856), while the volume of distribution at steady state was 284 L (95% CI 215–376) and 316 L (95% CI 142–707) (P = 0.780), with no statistically significant differences between the groups.

In this preliminary study, both the surgical ICU group (approximately 24 h) and the medical ICU group (beyond 24 h) showed no evidence of time-dependent accumulation of plasma remimazolam, indicating a generally stable pharmacokinetic profile under the examined conditions.

Trial registration: In compliance with the Japanese Clinical Trials Act, the study was classified as a Specified Clinical Trial owing to the use of unapproved pharmaceuticals, which were reviewed by a certified review board (CRB) and registered in the Japan Registry of Clinical Trials (jRCTs041200076) on December 15, 2020.

The online version contains supplementary material available at 10.1186/s40560-025-00840-9.

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