2012
DOI: 10.1213/ane.0b013e318241f68a
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A Placebo- and Midazolam-Controlled Phase I Single Ascending-Dose Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Remimazolam (CNS 7056)

Abstract: Population pharmacokinetic and pharmacodynamic models developed for remimazolam and midazolam fitted the observed data well. Simulations based on these models show that remimazolam delivers extremely rapid sedation, with maximal effect being reached within 3 minutes of the start of treatment. This property will enable maintenance doses to be given more accurately than with slower-acting drugs. No covariate effects considered to be clinically relevant were observed, suggesting that dosing by body weight may off… Show more

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Cited by 164 publications
(159 citation statements)
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“…The compartmental models that assume that the drug is distributed instantaneously throughout the central compartment are only valid with compounds whose distribution and clearance kinetics are relatively slow compared with the blood flow. This was not the case of remimazolam, which showed significantly higher venous concentrations than arterial ones (ratio >1, 44) [34]. Only a recirculatory pharmacokinetic model including both venous and arterial compartments, a cardiac blood/pulmonary compartment for the dose and clearance from the peripheral compartment was able to fit the data.…”
Section: Basic Pharmacokinetic Concepts and Some Clinical Applicationsmentioning
confidence: 88%
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“…The compartmental models that assume that the drug is distributed instantaneously throughout the central compartment are only valid with compounds whose distribution and clearance kinetics are relatively slow compared with the blood flow. This was not the case of remimazolam, which showed significantly higher venous concentrations than arterial ones (ratio >1, 44) [34]. Only a recirculatory pharmacokinetic model including both venous and arterial compartments, a cardiac blood/pulmonary compartment for the dose and clearance from the peripheral compartment was able to fit the data.…”
Section: Basic Pharmacokinetic Concepts and Some Clinical Applicationsmentioning
confidence: 88%
“…Only a recirculatory pharmacokinetic model including both venous and arterial compartments, a cardiac blood/pulmonary compartment for the dose and clearance from the peripheral compartment was able to fit the data. Three-and four-compartment mammillary models gave much poorer fits [34].…”
Section: Basic Pharmacokinetic Concepts and Some Clinical Applicationsmentioning
confidence: 97%
See 1 more Smart Citation
“…Other intravenous agents that accumulate significantly and are not suitable for use by infusion or multiple bolus administration outside of the ICU are morphine, midazolam, and thiopentone. Perhaps the most promising drug, particularly with regard to pharmacokinetics and dynamics, is remimazolam, which is metabolized by nonspecific tissue esterases, and has a fast onset and offset of effect [1,2]. This drug is currently undergoing further phase II and III evaluation.…”
Section: Choice Of Agentsmentioning
confidence: 99%
“…I n this issue of the journal, Wiltshire et al 1 report the pharmacokinetics and pharmacodynamics of a promising new benzodiazepine, remimazolam (CNS 7056), that has a rapid onset of effect and a short duration of action. As part of the design of their study, and for the convenience of the volunteer subjects, the investigators switched from arterial to venous blood sampling after the initial sampling period.…”
mentioning
confidence: 99%