Metabolic profile of oxazepam and related benzodiazepines: clinical and forensic aspects

Anxiolytic drugs, namely benzodiazepines, are the most commonly used psychoactive substances since anxiety disorders are prevalent mental disorders particularly in the Western world. Oxazepam is a short-acting benzodiazepine and one of the most frequently prescribed anxiolytic drugs. It is also the active metabolite of a wide range of other benzodiazepines, such as diazepam, ketazolam, temazepam, chlordiazepoxide, demoxazepam, halazepam, medazepam, prazepam, pinazepam, and chlorazepate. Therefore, relevant clinical and forensic outocomes may arise, namely those related to interference in driving performance. It is clinically available as a racemic formulation, with S-enantiomer being more active than R-enantiomer. In humans, it is mainly polimorphically metabolized by glucuronide conjugation at the 3-carbon hydroxyl group, yielding stable diastereomeric glucuronides (R- and S-oxazepam glucuronide). Relevant metabolic and stereoselective interspecies differences have been reported. In this work, the pharmacokinetics of oxazepam with particular focus on metabolic pathways is fully reviewed. Moreover, the metabolic profile of other prescribed benzodiazepines that produce oxazepam as a metabolite is also discussed. It is aimed that knowing the metabolism of oxazepam and related benzodiazepines may lead to the development of new analytical strategies for its early detection and help in further toxicological and clinical interpretations.