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  • Title: Benzodiazepines: a summary of pharmacokinetic properties.
    Author: Greenblatt DJ, Shader RI, Divoll M, Harmatz JS.
    Journal: Br J Clin Pharmacol; 1981; 11 Suppl 1(Suppl 1):11S-16S. PubMed ID: 6133528.
    Abstract:
    1 The onset and duration of action of benzodiazepines after single oral doses depend largely on absorption rate and extent of distribution, respectively. 2 The rate and extent of accumulation during multiple dosage depend on elimination half-life and clearance. A framework is proposed for classification of benzodiazepines according to elimination half-life. 3 Long-acting benzodiazepines have half-life values usually exceeding 24 hours. Drugs in this category have long-acting pharmacologically active metabolites (often desmethyldiazepam), accumulate extensively during multiple dosage, and may have impaired clearance in the elderly and those with liver disease. 4 Intermediate and short-acting benzodiazepines have half-life values from 5-24 hours. Active metabolites are uncommon. Accumulation during multiple dosage is less extensive than with the long-acting group, and diminishes as the half-life becomes shorter. Age and liver disease have a small influence on metabolic clearance. 5 The half-life of ultrashort acting benzodiazepines is less than 5 hours. These drugs are essentially non-accumulating. 6 Pharmacokinetic classification may assist in understanding of differences among benzodiazepines, but does not explain all of their clinical actions.
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