What is it about?
Modern medicine is almost unthinkable without sedation and general anesthesia. The ideal anesthetic modality should allow easy control of its duration of activity. Remimazolam is a new intravenous benzodiazepine-type drug that stands out by fast onset and termination of action. This is accomplished by a specific metabolic feature: Its activity is rapidly terminated by an enzyme termed carboxylesterase-1, mostly located in the liver. The resulting metabolite is entirely inactive; it undergoes further metabolism to a trivial extent, derivatives appearing in human blood and urine at negligible proportions only.
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Why is it important?
Fast recovery from sedation and a low potential of interactions with other drugs, both as a victim and a perpetrator, are favorable features offered by remimazolam. There is no indication of a pharmacolo¬gically active metabolite, so that there is no protracted sedation carried forward by derivatives. The spectrum of metabolites found in vivo suggests that fast metabolic inactivation by carboxylesterase-1 is by far the predominant determinant of remimazolam´s elimination and, therefore, duration of its sedative effect. The central role of carboxylesterase-1 also implies that drug-drug interactions via other drug-metabolizing enzymes such as the family of cytochrome P450 enzymes are not part of the safety profile of remimazolam.
Perspectives
This is an in-depth analysis of the metabolic fate of remimazolam in the patient body demonstrating the predominant role of carboxylesterase-1. It presents the results of years-long research efforts and we are glad to have been able now to unravel the background of unique drug properties anticipated some twenty years ago. Fast and short-lasting sedation and anesthesia mean less burden on the patient and less occupancy of institutional resources. As an example, patients will be ready for dis-charge comparatively fast after an endoscopic intervention. That other pathways such as cytochrome P450-mediated reactions are of no relevance to remimazolam metabolism also helps to understand why remimazolam´s potential of interactions with other drugs is negligible, a feature borne out by other research and a subject of upcoming publications.
Karl-Uwe Petersen
Read the Original
This page is a summary of: The Metabolism of the New Benzodiazepine Remimazolam, Current Drug Metabolism, February 2024, Bentham Science Publishers,
DOI: 10.2174/0113892002301026240318060307.
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