Benzodiazepine Metabolism: An Analytical Perspective

Abstract

Benzodiazepines are currently among the most frequently prescribed drugs all over the world. They act as anxiolytics, sedatives, hypnotics, amnesics, antiepileptics and muscle relaxants. Despite their common chemical scaffold, these drugs differ in their pharmacokinetic and metabolic properties. In particular, they are biotransformed by different cytochrome P450 isoforms and also by different UDP-glucuronosyltransferase subtypes. The most important studies on the metabolic characteristics of several 1,4-benzodiazepines, carried out from 1998 onwards, are reported and briefly discussed in this review. Moreover, the analytical methods related to these studies are also described and commented upon and their most important characteristics are highlighted. Most methods are based on liquid chromatography, which provides wide applicability and good analytical performance granting high precision, accuracy and feasibility. Mass spectrometry is gaining widespread acceptance, particularly if the matrix is very complex and variable, such as human or animal blood. However, spectrophotometric detection is still used for this purpose and can grant sufficient selectivity and sensitivity when coupled to suitable sample pre-treatment procedures. A monograph is included for each of the following benzodiazepines: alprazolam, bromazepam, brotizolam, clotiazepam, diazepam, etizolam, flunitrazepam, lorazepam, midazolam, oxazepam and triazolam.

Antiseizure Activity of Midazolam in Mice Lackingδ-Subunit Extrasynaptic GABAAReceptors

“…A meta-analysis has confirmed that midazolam by any route is superior to diazepam (McMullan et al, 2010). Midazolam offers several unique advantages over other benzodiazepines, including its rapid onset of action, short duration, water solubility, and extended shelf life (Mandrioli et al, 2008). Midazolam has a maximum shelf life of 2-3 years at room temperature.…”

“…Midazolam is a benzodiazepine antiseizure agent with rapid onset and short duration of action (Mandrioli et al, 2008). It is administered intravenously or intramuscularly to control acute seizures and status epilepticus (Galvin and Jelinek, 1987;Silbergleit et al, 2011;Reddy, 2014).…”

Redetermination of the structure of 7-chloro-1,3-dihydro-1-methyl-5- phenyl-1,4-benzodiazepin-2(3H)-one, C16H13ClN2O

“…In addition, it possesses anticonvulsant, hypnotic and skeletal muscle relaxant properties. The pharmacological action of diazepam enhances the effect of the neurotransmitter GABA by binding to the benzodiazepine site on the GABA A receptor (via the constituent chlorine atom) leading to central nervous system depression [1,2]. The structure of the title compound has been reported earlier [3], however, at room temperature only.…”

Experimentation on Hibiscus rosa Flower Mucilage as a Potential Nasal Mucoadhesive its Characterization as an In-situ Gel for some Anxiolytics

“…Pluronic F127 is widely used as a thermosensitive gelling agent since it is non-toxic, non-irritating, poses good release characteristics and biocompatible with other chemicals. 2,3 In the present investigation, mucilage isolated from Hibiscus flowers (Hibiscus rosa sinensis) was used as a mucoadhesive agent along with Pluronic F127 to prepare mucoadhesive in situ nasal gels containing alprazolam and to characterise them accordingly, in terms of texture profile analysis, viscosity, mucoadhesive strength, in vitro release profile, in vivo absorption kinetics and histological studies. Mucilages isolated from Hibiscus rosa used in formulations is compared with synthetic polymers hydroxypropyl methyl cellulose (HPMC) and Carbopol 934 (C-934).…”