Sex-related differences in blood concentrations and emergence profiles following total intravenous anesthesia with remimazolam and remifentanil

Abstract Remimazolam is a novel, short-acting benzodiazepine, which is characterized by rapid onset and quick recovery. The clinical efficacy and metabolism of many intravenous anesthetics are known to be influenced by sex; however, the effects of sex on the anesthetic efficacy and metabolism of remimazolam remain unclear. This prospective observational study examined sex-related differences in pharmacokinetics and emergence profiles after total intravenous anesthesia was induced with remimazolam and remifentanil in patients undergoing oral and maxillofacial surgery. Thirty-five American Society of Anesthesiologists Physical Status 1 adults (19 females, 16 males), aged 18–49 years, received standardized dosing based on their actual body weights. Serum remimazolam concentrations were measured at the end of administration and immediately before extubation using high-performance liquid chromatography. Although the emergence time did not differ significantly between the sexes, the mean emergence time of the females was approximately 80 s shorter. Serum remimazolam concentrations were significantly lower in females at both measurement time points (p < 0.001). This may suggest that remimazolam is metabolized more rapidly in women. Although these sex-related pharmacokinetic differences did not affect the time to awakening under combined remimazolam and remifentanil anesthesia, clinicians should be aware of potential sex differences in the pharmacokinetics of remimazolam.