Remimazolam İçin Optimal Dozaj Stratejileri Çeşitli Hasta Popülasyonlarında: Klinik Bir Derleme İncelemesi

Özet (abstract)

Abstract: Remimazolam is an ultra-short-acting benzodiazepine that is hydrolyzed by carboxylesterase 1 (CES1) to the inactive metabolite CNS 7054. Since regulatory approval in 2020 it has been adopted globally for procedural sedation and general anesthesia, supported by an expanding evidence base of randomized trials, population pharmacokinetic/pharmacodynamic (PK/PD) modeling studies, dose-finding sequential-allocation analyses, and meta-analyses. Synthesizing 92 studies published between January 2020 and April 2026, this narrative review defines dose optimization across diverse populations. For adult procedural sedation, a fixed 5 mg initial bolus followed by 2.5 mg maintenance titrations achieves moderate sedation with a hemodynamic and respiratory profile that compares favorably with propofol, whereas general anesthesia requires an induction rate of 6 to 12 mg kg − 1 h − 1 followed by maintenance at 1.0– 2.0 mg kg − 1 h − 1 . Dosing demands a 25– 30% reduction in the elderly (≥ 65 years), higher weight-adjusted requirements in pediatric patients (1– 18 years), and lean or corrected body weight scalars in obesity, while severe hepatic impairment reduces clearance by approximately 38% and opioid co-administration yields a 15– 63% synergistic reduction in effective concentrations. Several quantitative estimates, however, derive from single-center trials with fewer than 30 participants per arm that have not been externally validated. To help clinicians weigh these recommendations, each population-level dosing estimate is graded by the strength and external validity of its supporting evidence (A, B, or C); most special-population point estimates rest on single-center studies (grade C) and are best regarded as starting points rather than established standards. Crucially, the halted Japanese Phase II intensive care unit trial (ONO-2745-04) serves as a key safety counter-narrative: continuous infusions exceeding 24 hours in critically ill patients may be associated with drug accumulation and delayed emergence, suggesting that organ-independent clearance may not be guaranteed when CES1 activity is compromised. Major evidence gaps persist for infants under one year of age, long-duration anesthesia, CES1 polymorphisms, and non-East-Asian populations. Keywords: remimazolam, dosing, procedural sedation, population pharmacokinetics, pharmacodynamics, special populations

Yazarların özeti; kaynağından alınmıştır. Drug Design Development and Therapy, 2026 · DOI ↗