Journal of Forensic and Legal Medicine
Volume 14, Issue 6 , Pages 348-351 , August 2007

Metabolic interaction between ethanol, high-dose alprazolam and its two main metabolites using human liver microsomes in vitro

  • Einosuke Tanaka

      Affiliations

    • Department of Legal Medicine, Institute of Community Medicine, University of Tsukuba, Ibaraki-ken 305-8575, Japan
    • Corresponding Author InformationCorresponding author. Address: Department of Legal Medicine, Institute of Community Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki-ken 305-8575, Japan. Tel./fax: +81 29 853 3057.
  • ,
  • Takako Nakamura

      Affiliations

    • Department of Legal Medicine, Institute of Community Medicine, University of Tsukuba, Ibaraki-ken 305-8575, Japan
  • ,
  • Masaru Terada

      Affiliations

    • Department of Legal Medicine, School of Medicine, Toho University, 5-21-16 Omorinishi, Otaku, Tokyo 143-8540, Japan
  • ,
  • Tatsuo Shinozuka

      Affiliations

    • Department of Legal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
  • ,
  • Katsuya Honda

      Affiliations

    • Department of Legal Medicine, Institute of Community Medicine, University of Tsukuba, Ibaraki-ken 305-8575, Japan

Received 17 April 2006 ,Revised 21 August 2006 ,Accepted 17 November 2006.

References 

  1. In:  Lance LL,  Lacy CF,  Goldman MP,  Armstrong LL editor. Quick look drug book. New York: Lippincott Williams & Wilkins; 2001;p. 2
  2. National Research Institute of Police Science: annual case reports of drug and toxic poisoning in Japan (1990–2004), No. 33–47 [in Japanese].
  3. Tanaka E, Nakamura T, Terada M, Shinozuka T, Honda K. A study of the in vitro interaction between ethanol, and triazolam and its two metabolites using human liver microsomes. J Clin Forensic Med. 2005;12:245–248
  4. Tanaka E, Nakamura T, Terada M, Shinozuka T, Honda K. Preliminary study of the in vitro interaction between alcohol, high-dose flunitrazepam and its three metabolites using human liver microsomes. Basic Clin Pharmacol Toxicol. 2005;96:88–90
  5. Hall MA, Robinson CA, Brissie RM. High-performance liquid chromatography of alprazolam in postmortem blood using solid-phase extraction. J Anal Toxicol. 1995;19:511–513
  6. Jenkins AJ, Levine B, Locke JL, Smialek JE. A fatality due to alprazolam intoxication. J Anal Toxicol. 1997;21:218–220
  7. Michaud K, Augsburger M, Romain N, Giroud C, Mangin P. Fatal overdose of tramadol and alprazolam. Forensic Sci Int. 1999;105:185–189
  8. Kintz P, Villain M, Cheze M, Pepin G. Identification of alprazolam in hair in two cases of drug-facilitated incidents. Forensic Sci Int. 2005;53:222–226
  9. Winek CL, Wahba WW, Winek CL, Balzer TW. Drug and chemical blood-level data 2001. Forensic Sci Int. 2001;122:107–123
  10. Wennerholm A, Allqvist A, Svensson JO, Gustafsson LL, Mirghani RA, Bertilsson L. Alprazolam as a probe for CYP3A using a single blood sample: pharmacokinetics of parent drug, and of alpha- and 4-hydroxy metabolites in healthy subjects. Eur J Clin Pharmacol. 2005;61:113–118
  11. Galetin A, Brown C, Hallifax D, Ito K, Houston JB. Utility of recombinant enzyme kinetics in prediction of human clearance: impact of variability, CYP3A5, and CYP2C19 on CYP3A4 probe substrates. Drug Metab Dispo. 2004;32:1411–1420
  12. Smith RB, Kroboth PD. Influence of dosing regimen on alprazolam and metabolite serum concentrations and tolerance to sedative and psychomotor effects. Psychopharmacology (Berl). 1987;93:105–112
  13. von Moltke LL, Greenblatt DJ, Court MH, Duan SX, Harmatz JS, Shader RI. Inhibition of alprazolam and desipramine hydroxylation in vitro by paroxetine and fluvoxamine: comparison with other selective serotonin reuptake inhibitor antidepressants. J Clin Psychopharmacol. 1995;15:125–131
  14. Hall J, Naranjo CA, Sproule BA, Herrmann N. Pharmacokinetic and pharmacodynamic evaluation of the inhibition of alprazolam by citalopram and fluoxetine. J Clin Psychopharmacol. 2003;23:349–357
  15. Lieber CS. Mechanisms of ethanol–drug–nutrition interactions. J Toxicol Clin Toxicol. 1994;32:631–681
  16. Lieber CS. Susceptibility to alcohol-related liver injury. Alcohol Alcoholism. 1994;2:315–326
  17. Kitson KE. Ethanol and acetaldehyde metabolism: past, present, and future. Alcohol Clinical Exp Res. 1995;20:82A–92A
  18. Asai H, Imaoka S. Microsomal ethanol oxidizing system activity by human hepatic cytochrome P450’s. J Pharmacol Exp Therap. 1996;277:1004–1009
  19. Song BJ. Ethanol-inducible cytochrome P450 (CYP2E1): biochemistry, molecular biology and clinical relevance: 1996 up-date. Alcohol Clinical Exp Res. 1996;20:138A–146A
  20. Linnoila M, Stapleton JM, Lister R, Moss H, Lane E, Granger A, et al. Effects of single doses of alprazolam and diazepam, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers. Eur J Clin Pharmacol. 1990;39:21–28
  21. Michaud K, Augsburger M, Romain N, Giroud C, Mangin P. Fatal overdose of tramadol and alprazolam. Forensic Sci Int. 1999;105:185–189

PII: S1752-928X(06)00273-3

doi: 10.1016/j.jflm.2006.11.004

Journal of Forensic and Legal Medicine
Volume 14, Issue 6 , Pages 348-351 , August 2007