[The influence of plasma protein binding on distribution and pharmacological activity of tranquilizers of the benzodiazepine group (author's transl)]

Abstract

This paper discusses the problem if the plasma protein binding of benzodiazepine derivatives can influence distribution and pharmacological activity of the drugs. The distribution of the benzodiazepines in the organism is influenced not only by the plasma protein binding of the drugs, but also by several other factors, especially since the drugs are mostly lipophilic. Thus, an effect of the plasma protein binding on the distribution can only be expected if the benzodiazepine derivative is highly bound to the plasma proteins. Thus results have been shown only for diazepam and chlordiazepoxid, which indicate an effect of the plasma protein binding on distribution and pharmacological activity, for example the existence of a direct correlation between unwanted CNS depressions and low plasma albumin concentrations and a direct correlation between the plasma protein binding and the biological half-life. There are no observations available on a displacement of other drugs from their binding to plasma proteins by benzodiazepines. The observed displacement of thyroid hormones from their binding to plasma proteins seems to have only a significance for thyroid function tests in vitro. It was shown that benzodiazepines decrease the amount of L-tryptophan bound to serum albumin in vitro and in vivo and increased therewith the L-tryptophan concentration in the brain. At present it can not be confirmed if these observations bear any significance on the pharmacological activity of the drugs. But these experiments demonstrate the significance of the use of albumin as a model for the interaction of drugs with tissue or receptorproteins.