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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 25 (1983), S. 247-251 
    ISSN: 1432-1041
    Keywords: midazolam ; CSF penetration ; pharmacokinetics ; benzodiazepines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The passage of midazolam, a new benzodiazepine derivative with highly water-soluble salts, into cerebrospinal fluid (CSF) was studied after a single oral dose of 15 mg (n=23), a single i.m. injection of 0.075 or 0.150 mg/kg (n=8), or a single i.v. dose of 0.075 mg/kg (n=26). Contrary to previous studies of diazepam and flunitrazepam, the rapid clinical effect of midazolam cannot be explained by rapid passage into human lumbar CSF. In only four cases following intravenous injection was there a measurable amount of drug in lumbar CSF (lower limit of assay sensitivity=2 ng/ml). After both oral (n=10) and intramuscular (n=8) administration, midazolam was rapidly absorbed, with attainment of the peak serum level after about 0.5 h. The pharmacokinetic parameters following i.v. injection of midazolam (n=6) explain its rapid but brief duration of action.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Diazepam Therapy ; Enzyme Induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The plasma diazepam, N-demethyldiazepam, and free oxazepam concentrations were studied in 12 neurotic outpatients during subchronic use, in 14 outpatients after chronic use, and in 8 test subjects after an acute intravenous administration. There are several reasons for believing that diazepam may induce its own metabolism in man: 1. The decrease in diazepam and N-demethyldiazepam concentrations in the plasma after 1–6 weeks therapy. 2. Comparatively low plasma diazepam concentrations in patients who had taken diazepam for several months or years. 3. Much higher concentrations of N-demethyldiazepam, the main metabolite, after intravenously given diazepam in chronic users of diazepam as compared to controls. 4. The decrease in the ability to form N-demethyldiazepam after abstinence, when diazepam was administered intravenously to a chronic user of diazepam before and after the abstinence of the drug. Diazepam should be administered in small doses and for short periods of time only, or intermittently.
    Type of Medium: Electronic Resource
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