Clinical pharmacokinetics of the newer benzodiazepines

New benzodiazepine derivatives continue to be developed and introduced into clinical use. The pharmacokinetic properties of these newer drugs can best be understood by their categorisation according to range of elimination half-life and pathway of metabolism (oxidation versus conjugation). Clobazam and halazepam are long half-life (and therefore accumulating) anxiolytics metabolised by oxidation. Alprazolam and clotiazepam also are oxidised compounds but have short to intermediate half-life values and therefore produce considerably less accumulation. Temazepam and lormetazepam are hypnotic agents with intermediate half-lives but metabolised by conjugation. The most unique of the newer benzodiazepines are the ultra-short half-life (oxidised) compounds midazolam, triazolam and brotizolam, which are essentially non-accumulating during multiple dosage.