In vitro effects of remimazolam on human platelet function and a possible flumazenil-sensitive and non-sensitive pathway.

PURPOSE: Remimazolam is a novel benzodiazepine intravenous sedative that is reversible by flumazenil. The related drug midazolam inhibits platelet aggregation through multiple pathways, but the effect of remimazolam on platelet function remains unclear. The aim of this study is to investigate the effect of remimazolam (Anerem®) on platelet function in vitro.

METHODS

Venous blood from healthy volunteers was incubated with remimazolam (3-300 μg/mL) in platelet-rich plasma and whole blood. Dextran, an excipient in Anerem®, was also investigated at corresponding concentrations (12-1200 μg/mL). Platelet aggregation was assessed by light transmission aggregometry using adenosine diphosphate (ADP) stimulation, and P-selectin expression was measured by flow cytometry. Platelet counts and mean platelet volume (MPV) were determined using an automated hematology analyzer. The same effects were also investigated in the presence of flumazenil (0.6-30 ng/mL).

RESULTS

At 3 μg/mL, corresponding to clinical plasma levels, remimazolam showed no effect on platelet function. However, at 300 μg/mL, both ADP-induced platelet aggregation and P-selectin expression were significantly inhibited. The inhibition of aggregation was antagonized by flumazenil, but the reduced P-selectin expression was not reversed. Neither dextran nor flumazenil alone showed significant effects, and platelet count and MPV remained unchanged.

CONCLUSION

Remimazolam (Anerem®) did not affect human platelet function at clinically relevant concentrations. However, it inhibited platelet aggregation at supra-clinical concentrations and this effect was partially mediated by a flumazenil-sensitive pathway. These findings provide pharmacological insight into the effects of remimazolam on platelets; however, the clinical relevance of these observations requires further evaluation in future in vivo and clinical studies.