Pharmacology - Benzodiazepines: A Summary of Pharmacokinetic Properties (1981)

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Description:
British Journal of Pharmacology 1981;11 Suppl 1:11S-16S

Greenblatt DJ, Shader RI, Divoll M, Harmatz JS.

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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