Pharmacodynamics of Benzodiazepines After Single Oral Doses: Kinetic and Physiochemical Correlates

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Abstract
Differences among various benzodiazepines in onset and intensity of action after single oral doses are not attributable to differences in blood brain barrier permeability. When given parenterally all benzodiazepines rapidly enter brain tissue and have a rapid onset of action, indicating that passage from blood to brain is not the rate-limiting factor (Arendt et al. 1983). Rather it is the difference in rate of absorption — passage from the gastrointestinal tract to systemic blood — that largely determines the onset of action after single oral doses. This difference in absorption rate in turn depends on the relative lipophilicity as well as the characteristics of the pharmaceutical formulation. There are benefits and disadvantages associated with rapid as well as with slow absorption profiles, depending on the clinical situation and the patient’s expectations and particular pattern of drug sensitivity. The suggestion that a drug “works promptly but does not produce initial euphoria” is contradictory, since rapid absorption is the mechanism for both of these effects.