title: Metabolic Profile of Flunitrazepam: Clinical and Forensic Toxicological Aspects.
abstract: Flunitrazepam (FNZ) is a potent hypnotic, sedative, and amnestic drug used to treat insomnia and as a pre-anesthetic agent. The illicit practice in drug-facilitated sexual assault led to important clinical and forensic concerns.
  
  
  
  In this work the metabolism of FNZ, and pharmacological- and toxicological-related effects, were fully reviewed.
  
  
  
  FNZ and related known metabolizing enzymes and metabolites were searched in books and in PubMed (U.S. National Library of Medicine) without a limiting period.
  
  
  
  Major metabolic pathways include N-demethylation, 3-hydroxylation, nitro-reduction, and further N-acetylation of the amino group, yielding N-desmethylflunitrazepam, 3-hydroxy-flunitrazepam, 7-aminoflunitrazepam, and 7-acetamidoflunitrazepam, respectively. A combination of these reactions may lead to the formation of 7-amino-N-desmethylflunitrazepam, 7-acetamido-N-desmethylflunitrazepam, 3- hydroxy-7-aminoflunitrazepam, 3-hydroxy-7-acetamidoflunitrazepam, 3-hydroxy-N-desmethylflunitrazepam and glucuronide conjugates. Genotypic variations in enzymes, interactions with other drugs or stability of FNZ during storage can result in large interindividual variability in the toxicological results.
  
  
  
  It is aimed that knowing the metabolism of FNZ may lead to the development of new analytical strategies for early detection, since this drug is typically present in very low concentrations in blood and urine when used to facilitate sexual assault.
authors.affiliation: IINFACTS - Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal.|UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.|Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: Ricardo Jorge
authors.initials: RJ
authors.lastname: Dinis-Oliveira
mesh_terms: D065567:Absorption, Physiological; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000378:metabolism* / Q000493:pharmacokinetics; D005445:Flunitrazepam / Q000009:adverse effects* / Q000378:metabolism* / Q000493:pharmacokinetics; D005554:Forensic Medicine; D006801:Humans; D053858:Metabolic Networks and Pathways
chemical_list: D000928:Antidepressive Agents; D005445:Flunitrazepam
keywords: Flunitrazepam; genotypic variations; metabolism; pharmacokinetics; sexual assault.; toxicological analysis