Pharmacokinetic aspects of habituation to benzodiazepines

In state of tolerance to the sedative effect of nitrazepam (NTZ) its pharmacokinetic properties are changed: the absorption is slowed down, the elimination, in contrast, is accelerated due to the rapid biotransformation. The NTZ content in brain tissue is increased significantly with respect to the brain levels of animals treated with a single dose of NTZ. In animals of only moderate intensity of tolerance produced by oxazepam (OX) the brain concentrations of OX are correlated with the developed tolerance.