[Clinical pharmacokinetics of midazolam, flunitrazepam and diazepam (author's transl)].

Diazepam, flunitrazepam and midazolam have different pharmacokinetic properties, their biological halflives for instance, being 24 to 48 hours, 4,5 hours and 2,5 hours respectively. Moreover, the total plasma clearances calculated for these drugs resulted in 30 ml/min for diazepam, 250 ml/min for flunitrazepam and 450 ml/min for midazolam. On the other hand, all three drugs were found to have nearly the same volumes of distribution (V1: 25 l, VdSS: 80-100 l). A tissue binding of over 90% of the drugs applied can further be computed from their high plasmaprotein binding action and their volumes of distribution. Of the 3 benzodiazepines investigated, diazepam reveals extremely complex pharmacokinetic effects which vary the duration of pharmacological responses very widely; besides drug interaction, enzyme induction and -inhibition it gives rise to the active metabolite N-desmethyl-diazepam (biological halflife 50 to 120 hours). In this respect however, the metabolic products of flunitrazepam and midazolam seem to be of minor clinical importance only. The pharmacokinetics of flunitrazepam will be presented as an example to discuss several modes of dosage.