General Tranquilizers

Current methodology for determining plasma levels of diazepam and its active metabolites employs electron-capture gas chromatography and can measure 1- to 10-ng quantities (). When a group of people are administered diazepam at a particular dose, there is a wide range of plasma concentrations of diazepam (). This range, in 13 subjects administered 15 mg of oral diazepam daily for a week or more, is 16 to 400 ng/ml (). Garattini et al. () found a range of 10 to 250 ng/ml in 27 subjects given a single 15-mg oral dose. A half-life of 38 to 92 minutes has been measured by this group in five female subjects. Kleijn et al. () calculated a half-life of 20 to 42 hours after 10 mg three times a day, about 0.5 mg/kg/day orally in five subjects. This great variability in plasma concentration is a major problem in interpreting drug effects on human performance. Perhaps the factors that influence plasma concentration curves can be identified and controlled. With seven subjects, Linnoila et al. () showed that ingestion of food increases plasma levels of diazepam 6, 7, and 8 hours after intravenous administration of 0.3 mg of diazepam per kg. They suggest that enterohepatic recycling of diazepam is occurring. Kleijn et al. () Read more […]