Plasma concentrations of flurazepam and midazolam in chronic insomniacs during 14-day use and their relationship to therapeutic effects and next-day performance and mood. 1990

E Ellinwood, and M Linnoila, and G Marsh
Duke University Medical Center, Durham, North Carolina 27710.

Blood samples were drawn from each of 99 chronic insomniacs twice during washout (days -20 and -6) and six times during the study (mornings after study nights -1, 1, 2, 7, 13, and 14) to examine the relationship between morning-after drug plasma levels, sleep efficiency, next-day mood, and performance. Patients in the four treatment groups received either flurazepam 30 mg, flurazepam 15 mg, midazolam 15 mg, or placebo. Plasma drug concentrations of N-desalkylflurazepam and midazolam were measured by electron-capture gas chromatography. Values of midazolam during the 14-day study were at or near the sensitivity limit of the assay and were not used in the calculations. Levels of N-desalkylflurazepam increased as expected during the 14 days. Mean level for the high-dose flurazepam group was approximately twice that of the low-dose group. The main consistency in the correlations, which were found on days 13 and 14, was that the high-dose desalkylflurazepam concentrations had a negative correlation with two independent measures of sleep latency. However, otherwise there was little or no relationship between N-desalkylflurazepam levels and sleep efficiency or next-day behavior. Issues of tolerance, individual variability in baseline and response, and their contribution to the findings are discussed.

UI MeSH Term Description Entries
D007319 Sleep Initiation and Maintenance Disorders Disorders characterized by impairment of the ability to initiate or maintain sleep. This may occur as a primary disorder or in association with another medical or psychiatric condition. Disorders of Initiating and Maintaining Sleep,Insomnia,Sleeplessness,Chronic Insomnia,DIMS (Disorders of Initiating and Maintaining Sleep),Early Awakening,Insomnia Disorder,Nonorganic Insomnia,Primary Insomnia,Psychophysiological Insomnia,Rebound Insomnia,Secondary Insomnia,Sleep Initiation Dysfunction,Transient Insomnia,Awakening, Early,Dysfunction, Sleep Initiation,Dysfunctions, Sleep Initiation,Insomnia Disorders,Insomnia, Chronic,Insomnia, Nonorganic,Insomnia, Primary,Insomnia, Psychophysiological,Insomnia, Rebound,Insomnia, Secondary,Insomnia, Transient,Insomnias,Sleep Initiation Dysfunctions
D008297 Male Males
D008874 Midazolam A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH. Dormicum,Midazolam Hydrochloride,Midazolam Maleate,Ro 21-3981,Versed,Hydrochloride, Midazolam,Maleate, Midazolam,Ro 21 3981,Ro 213981
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009483 Neuropsychological Tests Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. Aphasia Tests,Cognitive Test,Cognitive Testing,Cognitive Tests,Memory for Designs Test,Neuropsychological Testing,AX-CPT,Behavioral Assessment of Dysexecutive Syndrome,CANTAB,Cambridge Neuropsychological Test Automated Battery,Clock Test,Cognitive Function Scanner,Continuous Performance Task,Controlled Oral Word Association Test,Delis-Kaplan Executive Function System,Developmental Neuropsychological Assessment,Hooper Visual Organization Test,NEPSY,Neuropsychologic Tests,Neuropsychological Test,Paced Auditory Serial Addition Test,Repeatable Battery for the Assessment of Neuropsychological Status,Rey-Osterrieth Complex Figure,Symbol Digit Modalities Test,Test of Everyday Attention,Test, Neuropsychological,Tests, Neuropsychological,Tower of London Test,Neuropsychologic Test,Test, Cognitive,Testing, Cognitive,Testing, Neuropsychological,Tests, Cognitive
D011597 Psychomotor Performance The coordination of a sensory or ideational (cognitive) process and a motor activity. Perceptual Motor Performance,Sensory Motor Performance,Visual Motor Coordination,Coordination, Visual Motor,Coordinations, Visual Motor,Motor Coordination, Visual,Motor Coordinations, Visual,Motor Performance, Perceptual,Motor Performance, Sensory,Motor Performances, Perceptual,Motor Performances, Sensory,Perceptual Motor Performances,Performance, Perceptual Motor,Performance, Psychomotor,Performance, Sensory Motor,Performances, Perceptual Motor,Performances, Psychomotor,Performances, Sensory Motor,Psychomotor Performances,Sensory Motor Performances,Visual Motor Coordinations
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D005260 Female Females
D005479 Flurazepam A benzodiazepine derivative used mainly as a hypnotic. Apo-Flurazepam,Dalmadorm,Dalmane,Dormodor,Flurazepam Dihydrochloride,Flurazepam Hydrochloride,Flurazepam Mono-Perchlorate,Flurazepam Monohydrochloride,Staurodorm,Apo Flurazepam,Dihydrochloride, Flurazepam,Flurazepam Mono Perchlorate,Hydrochloride, Flurazepam,Mono-Perchlorate, Flurazepam,Monohydrochloride, Flurazepam

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