Population Pharmacokinetics of Remimazolam in Procedural Sedation With Nonhomogeneously Mixed Arterial and Venous Concentrations.

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.

Pharmacokinetics and pharmacodynamics of intranasal remimazolam-a randomized controlled clinical trial.

Purpose: Remimazolam is a novel and ultra-short-acting sedative currently developed for intravenous use in procedural sedation, general anesthesia, and ICU sedation. However, intravenous administration is not always appropriate, depending on the patient or setting. This study evaluated intranasal administration as a potential alternative route.

Population pharmacokinetic/pharmacodynamic modeling for remimazolam in the induction and maintenance of general anesthesia in healthy subjects and in surgical subjects.

Study Objective: To evaluate factors affecting variability in response to remimazolam in general anesthesia.

Design: Plasma concentration-time data from 11 Phase 1-3 clinical trials were pooled for the population pharmacokinetic (popPK) analysis and concentration-bispectral index (BIS) data were pooled from 8 trials for popPK-PD analysis. A 3-compartment model with allometric exponents on clearance and volume described remimazolam concentrations over time.

Potential strategy for assessing QT/QTc interval for drugs that produce rapid changes in heart rate: Electrocardiographic assessment of the effects of intravenous remimazolam on cardiac repolarization.

Aims: Remimazolam is a new, ultra-short-acting benzodiazepine developed for intravenous (IV) use during procedural sedation and in general anaesthesia. Two trials were conducted to characterize its effects on cardiac repolarization.

Methods: A thorough QT/QTc (TQT) study assessed electrocardiography effects of therapeutic and supratherapeutic doses of remimazolam and midazolam.

Time-to-Event Modeling for Remimazolam for the Indication of Induction and Maintenance of General Anesthesia.

Remimazolam is an ultra-short-acting benzodiazepine being investigated for induction and maintenance of general anesthesia and for procedural sedation. This dose-response analysis of 4 phase 2-3 studies evaluated covariates that may impact the pharmacodynamic profile (based on theoretical pharmacokinetic principles) and require dose adjustments in subpopulations, particularly elderly, and if remimazolam has cumulative properties. Covariates affecting the time to loss of consciousness and time to extubation were evaluated using Cox proportional hazards models.

Differential block of sensory neuronal voltage-gated sodium channels by lacosamide [(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide], lidocaine, and carbamazepine.

Voltage-gated sodium channels play a critical role in excitability of nociceptors (pain-sensing neurons). Several different sodium channels are thought to be potential targets for pain therapeutics, including Na(v)1.7, which is highly expressed in nociceptors and plays crucial roles in human pain and hereditary painful neuropathies, Na(v)1.

Lacosamide.

Lacosamide is a new chemical entity being investigated as an adjunctive treatment for epilepsy, as well as monotherapy for diabetic neuropathic pain. Lacosamide appears to have a dual mode of action: selective enhancement of sodium channel inactivation and modulation of collapsin response mediator protein-2. Rapidly and completely absorbed after oral administration, lacosamide has an elimination half-life of approximately 13 hours and a low potential for drug interactions.

Effects of the novel antiepileptic drug lacosamide on the development of amygdala kindling in rats.

Purpose: The current treatment of epilepsy focuses exclusively on the prophylaxis or suppression of seizures and thus provides merely a symptomatic treatment, without clear influence on the course of the disease. There is a need for new drugs that act at different molecular targets than currently available antiepileptic drugs (AEDs) and for new therapies designed to block the process of epileptogenesis. In recent years, different research lines have examined the epileptogenic process in order to understand the different stages in this process, and with the hope that early recognition and intervention could prevent the development or progression of epilepsy.