Drug-Drug Interaction Potential of Remimazolam: CYP 450, Transporters, and Protein Binding.

BACKGROUND

The ultra-short-acting benzodiazepine, remimazolam, is a new treatment modality for procedural sedation and general anesthesia. Its activity is terminated by carboxylesterase 1 (CES1).

OBJECTIVE

The objective of this study was to determine the drug-drug interaction (DDI) potential of remimazolam through mechanisms unrelated to its metabolizing enzyme, CES1.

METHODS

Conventional in vitro co-exposure experiments were conducted to study possible interactions of remimazolam and its primary metabolite, CNS7054, mediated by competitive binding to plasma protein or reactions with cytochrome P450 isoforms or drug transporters.

RESULTS

No relevant interactions of remimazolam or its metabolite with cytochrome P450 (CYP) isoforms at clinically relevant concentrations were identified. Likewise, standard experiments revealed no clinically relevant interactions with drug transporters and plasma proteins.

CONCLUSION

The present data and analyses suggest a very low potential of remimazolam for pharmacokinetic DDIs mediated by CYP isoforms, drug transporters, and protein binding.