Title:Metabolic Profile of Flunitrazepam: Clinical and Forensic Toxicological Aspects
VOLUME: 11 ISSUE: 1
Author(s):Ricardo Jorge Dinis-Oliveira*
Affiliation:Department of Sciences, University Institute of Health Sciences (IUCS)-CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra, PRD
Keywords:Flunitrazepam, metabolism, pharmacokinetics, toxicological analysis, genotypic variations, sexual assault.
Abstract:Background: 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.
Objective: In this work the metabolism of FNZ, and pharmacological- and toxicological-related effects,
were fully reviewed.
Methods: 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.
Results: 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.
Conclusion: 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.
