Remimazolam is a new ultra-short-acting benzodiazepine for procedural sedation and general anaesthesia. The pharmacokinetics and adverse effects of remimazolam were characterised in renally and hepatically impaired subjects compared with normal volunteers. Remimazolam pharmacokinetic properties were described by a three-compartment recirculatory model, with no relevant impact of hepatic or renal impairment and a low incidence of adverse events. Remimazolam has predictable pharmacokinetic properties, and does not require dose adjustments in subjects with hepatic or renal impairment. The selection of a safe and effective dose of sedative-hypnotics drugs for general anaesthesia and procedural sedation in patients with hepatic or renal impairment is challenging. Decreased elimination properties in patients with hepatic or renal dysfunction may lead to difficulties in anaesthesia management and postoperative recovery. Many intravenous sedatives and anaesthetics show a different pharmacokinetic (PK) profile in patients with hepatic or renal impairment, potentially resulting in increased exposure to the parent drug or a metabolite.

The half-life of benzodiazepines, for example can be twice as long in patients with hepatic failure compared with healthy subjects, whereas codeine or meperidine should be avoided in patients with severe renal impairment because of narcolepsy, respiratory arrest, etc. caused by accumulation of metabolites because of reduced renal elimination.As a consequence, careful dose adjustment may be required. Remimazolam (PAION, Aachen, Germany), an ultra-short-acting intravenous benzodiazepine, represents an alternative in the search for a safe shorter-acting anaesthetic providing sedation combined with fast onset and rapid recovery. Remimazolam is rapidly metabolised to an inactive metabolite by liver esterases, specifically by CES-1A. This metabolite is the only clinically relevant metabolite of remimazolam – it is the only metabolite that accounts for more than 10% of drug-related material at steady state.

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Mishita
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Journal of Clinical & Experimental Nephrology