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  • Title: [Benzodiazepines: significance of kinetics for therapy].
    Author: Ochs HR.
    Journal: Klin Wochenschr; 1983 Mar 01; 61(5):213-24. PubMed ID: 6405081.
    Abstract:
    The onset and duration of action of benzodiazepines after single oral doses depend largely on absorption rate and the rate and extent of distribution. 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. Long acting benzodiazepines have half-life values usually exceeding 24 h. 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. Intermediate and short-acting benzodiazepines have half-life values from 5-24 h and 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. The half-life of ultrashort-acting benzodiazepines is less than 5 h. These drugs are essentially nonaccumulating. Pharmacokinetic classification may assist in understanding differences among benzodiazepines, but does not explain all of their clinical actions.
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