Preliminary study of the in vitro interaction between alcohol, high-dose flunitrazepam and its three metabolites using human liver microsomes

Basic and Clinical Pharmacology and Toxicology

Volumn 96, Issue 1, 2005, Pages 88-90

  Tanaka, Einosuke ^a   Nakamura, Takako ^a   Terada, Tasaru ^a,b   Shinozuka, Tatsuo ^c   Honda, Katsuya ^a  

^a UNIVERSITY OF TSUKUBA   (Japan)

^b TOHO UNIVERSITY   (Japan)

^c KEIO UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXYFLUNITRAZEPAM; 7 AMINOFLUNITRAZEPAM; ALCOHOL; ALCOHOL DEHYDROGENASE; CYTOCHROME P450; CYTOCHROME P450 2C19; CYTOCHROME P450 2E1; CYTOCHROME P450 3A4; FLUNITRAZEPAM; NORFLUNITRAZEPAM; UNCLASSIFIED DRUG;

ALCOHOL CONSUMPTION; ALCOHOL METABOLISM; ARTICLE; CATABOLISM; CATALYSIS; CONTROLLED STUDY; DRUG ALCOHOL INTERACTION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME MECHANISM; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; IN VITRO STUDY; LIVER MICROSOME; METABOLITE; PRIORITY JOURNAL;

ANTI-ANXIETY AGENTS; BIOTRANSFORMATION; CENTRAL NERVOUS SYSTEM DEPRESSANTS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DRUG INTERACTIONS; ETHANOL; FLUNITRAZEPAM; HUMANS; MICROSOMES, LIVER; SPECTROPHOTOMETRY, ULTRAVIOLET;

EID: 13944256953     PISSN: 17427835     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1742-7843.2005.pto960113.x     Document Type: Article

References (22)

1. Asai, H. & S. Imaoka: Microsomal ethanol oxidizing system activity by human hepatic cytochrome P450's. J. Pharmacol. Exp. Ther. 1996, 277, 1004-1009.
2. Assaf, M. S. & M. S. Abdel-Rahman: Hepatotoxicity of flunitrazepam and alcohol in vitro. Toxicol. in Vitro 1999, 13, 393-401.
3. Barnas, C., M. Rossmann, H. Roessler, Y. Riemer & W. W. Fleischhacker: Benzodiazepines and other psychotropic drugs abused by patients in a methadone maintenance program: familiarity and preference. J. Clin. Psychopharmacol. 1992, 12, 397-402.
4. Daderman, A. M. & L. Lidberg: Flunitrazepam (Rohypnol) abuse in combination with alcohol causes premeditated, grievous violence in male juvenile offenders. J. Am. Acad. Psychiatry Law 1999, 27, 83-99.
5. Druid, H., P. Holmgren & J. Ahlner: Flunitrazepam: an evaluation of use, abuse and toxicity. For. Sci. Int. 2001, 122, 136-141.
6. Hermansson, G.: Report from the Sweden National Police School. Rikskriminalpolisen. Stockholm, 1998.
7. Hesse, L. M., K. Venkatakrishnan, L. L. von Moltke, R. I. Shader & D. J. Greenblatt: CYP3A4 is the major CYP isoform mediating the in vitro hydroxylation and demethylation of flunitrazepam. Drug Metab Dispos. 2001, 29, 133-140.
8. Kilicarslan, T., R. L. Haining, A. E. Rettie, U. Busto, R. F. Tyndale & E. M. Sellers: Flunitrazepam metabolism by cytochrome P450S 2C19 and 3A4. Drug Metab. Dispos. 2001, 29, 460-465.
9. Kitson, K. E.: Ethanol and acetaldehyde metabolism: past, present, and future. Alcohol Clin. Exp. Res. 1996, 20, 82A-92A.
10. Ko, J. W., Z. Desta, N. V. Soukhova, T. Tracy & D. Q. Flockharf. In vitro inhibition of the cytochrome P450 (CYP450) system by the antiplatelet drug ticlopidine: potent effect on CYP2C19and CYP2D6. Brit. J. Clin. Pharmacol. 2000 ,49, 343-351.
11. Lieber, C. S.: Susceptibility to alcohol-related liver injury. Alcohol Suppl. 1994, 2, 315-326.
12. National Research Institute of Police Science: Annual Case Reports of Drug and Toxic Poisoning in Japan (1990-2002), No. 33-45 (in Japanese).
13. Navaratnam, V. & F. Foong: Opiate dependence - the role of benzodiazepines. Curr. Med. Res. Opin. 1990, 11, 620-630.
14. Newton, D. J., R. W. Wang & A. Y. H. Lu: Cytochrome P450 inhibitors evaluation of specificities in the in vitro metabolism of therapeutics agents by human liver microsomes. Drug Metab. Dispos. 1995, 23, 154-158.
15. San, L., J. Tato, M. Torrens, C. Castillo, M. Farre & J. Cami: Flunitrazepam consumption among heroin addicts admitted for inpatient detoxification. Drug Alcohol Depend. 1993, 32, 281-286.
16. Simmons, M. M. & M. J. Cupp: Use and abuse of flunitrazepam. Ann. Pharmacother. 1998, 32, 117-119.
17. Smith, K. M., L. L. Larive & F. Romanelli: Club drugs: methylenedioxy-methampbetamine, flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate. Amer. J. Health Syst. Pharm. 2002, 59, 1067-1076.
18. Song, B. J.: Ethanol-inducible cytochrome P450 (CYP2E1): biochemistry, molecular biology and clinical relevance: 1996 up-date. Alcohol Clin. Exp. Res. 1996, 20, 138A-146A.
19. Tanaka, E. & S. Misawa: Pharmacokinetic interactions between acute alcohol ingestion and single doses of benzodiazepines, and tricyclic and tetracyclic antidepressants - an update. J. Clin. Pharm. Ther. 1998, 23, 331-336.
20. Tanaka, E.: Toxicological interactions between alcohol and benzodiazepines. J. Toxicol. Clin. Toxicol. 2002, 40, 69-75.
21. Yamamoto, H., A. Tanegashima, H. Hosoe & T. Fukunaga: Fatal acute alcohol intoxication in an ALDH2 heterozygote: a case report. For. Sci. Int. 2000, 112, 201-207.
22. Woods, J. H. & G. Winger: Abuse liability of flunitrazepam. J. Clin. Psychopharmacol. 1997, 17, 1S-57S.