remimazolam and Pain--Procedural

Remimazolam is an ultra-short acting benzodiazepine under development for procedural sedation and general anesthesia. Population pharmacokinetic analysis (PopPK) was conducted for remimazolam with arterial and venous samples previously, but results were limited by arterial-venous concentration differences and inaccurate central volume of distribution (V1) estimates. A new model was developed to describe covariate effects after accounting for arterial-venous differences. Arterial and venous plasma concentration-time data from 11 clinical trials were pooled for PopPK. Data from two constant-rate infusion studies were used to account for venous-to-arterial (VtoA) ratio within residual error and to accurately estimate V1. V1 and VtoA ratio from the pilot model were applied to the full dataset, where the optimal fixed/random effects and covariates were assessed. VtoA ratio was described using a maximum effect (E

Topics: Adult; Aged; Aged, 80 and over; Benzodiazepines; Biological Variation, Population; Clinical Trials as Topic; Datasets as Topic; Deep Sedation; Female; Healthy Volunteers; Humans; Infusions, Intravenous; Male; Middle Aged; Models, Biological; Pain, Procedural; Pilot Projects; Sex Factors; Young Adult