A Placebo- and Midazolam-Controlled Phase I Single Ascending-Dose Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Remimazolam (CNS 7056): Part II. Population Pharmacokinetic and Pharmacodynamic Modeling and Simulation

• Published in: Anesthesia and analgesia Vol. 115; no. 2; pp. 284 - 296
• Main Authors: Wiltshire, Hugh R., Kilpatrick, Gavin J., Tilbrook, Gary S., Borkett, Keith M.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD International Anesthesia Research Society 01.08.2012; Lippincott Williams & Wilkins
• Subjects: Adult; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Benzodiazepines - administration & dosage; Benzodiazepines - adverse effects; Benzodiazepines - blood; Benzodiazepines - pharmacokinetics; Biological and medical sciences; Computer Simulation; Consciousness - drug effects; Consciousness Monitors; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypnotics and Sedatives - administration & dosage; Hypnotics and Sedatives - adverse effects; Hypnotics and Sedatives - blood; Hypnotics and Sedatives - pharmacokinetics; Infusions, Intravenous; Male; Maryland; Medical sciences; Metabolic Clearance Rate; Midazolam - administration & dosage; Midazolam - adverse effects; Midazolam - blood; Midazolam - pharmacokinetics; Middle Aged; Models, Biological; Monte Carlo Method; Placebos; Treatment Outcome; Young Adult; Maryland; Simulation; Psychotropic; Single dose; Phase I trial; Benzodiazepine derivatives; Anesthesia; Hypnotic; Midazolam; Sedative; Pharmacokinetics; Modeling

A new benzodiazepine, remimazolam, which is rapidly metabolized by tissue esterases to an inactive metabolite, has been developed to permit a fast onset, a short, predictable duration of sedative action, and a more rapid recovery profile than currently available drugs. We report on modeling of the d...