Influence of ethanol on the metabolism of alprazolam

Expert Opinion on Drug Metabolism & Toxicology
Zhibin HuangYulan Rao

Abstract

Alprazolam is a commonly used benzodiazepine in clinical practice, and when coingested with ethanol, alprazolam can increase behavioral irritability and aggression. However, the mechanism of its interaction with ethanol remains unknown. The pharmacokinetics of alprazolam was studied in vivo in rat experiments involving the simultaneous administration of alprazolam and ethanol, and the interactions between ethanol and alprazolam were investigated in vitro in human liver microsomes. In silico molecular docking was applied to analyze the change in the CYP3A4-alprazolam-binding conformation when ethanol was coadministered with alprazolam. Compared with alprazolam administered alone (2 mg/kg), the Cmax of alprazolam increased when ethanol was simultaneously administered at 3 g/kg. The concentrations of alprazolam significantly increased by 39%, 17%, 105%, and 642% at 5, 10, 30, and 120 min intervals in the brain when coadministered with ethanol, respectively. Molecular docking results suggested that the conformation of CYP3A4 with alprazolam changed when ethanol was bound to the SER119 residue, which seems critical in the process of CYP3A4-alprazolam binding. Ethanol might increase the toxicity of alprazolam by inhibiting the activi...Continue Reading

References

Oct 1, 1976·British Journal of Anaesthesia·H W Elliott
Feb 1, 1990·Pharmacology, Biochemistry, and Behavior·A W ChanM L Penetrante
Jan 1, 1982·Journal of Studies on Alcohol·L J O'BrienR C Tessler
Sep 1, 1993·Journal of Studies on Alcohol. Supplement·A J Bond, J C Silveira
Dec 13, 1995·Journal of Affective Disorders·A J BondP Shine
Jul 17, 1998·Neuroreport·H TatebayashiT Narahashi
May 7, 2002·Journal of Toxicology. Clinical Toxicology·Einosuke Tanaka
May 31, 2003·Human & Experimental Toxicology·Anna KoskiErkki Vuori
Jun 20, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kiran C PatkiDavid J Greenblatt
May 6, 2004·Vascular Medicine·Charalambos VlachopoulosChristodoulos Stefanadis
Jun 23, 2004·British Journal of Clinical Pharmacology·Geoffrey K IsbisterIan M Whyte
Jul 6, 2010·Biochimica Et Biophysica Acta·Vitor H TeixeiraPaulo J Martel
May 21, 2014·Journal of the Formosan Medical Association = Taiwan Yi Zhi·Tzu-Ting ChenCheng-Fang Yen
Dec 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Irina F Sevrioukova, Thomas L Poulos
Aug 5, 2017·Journal of Addiction Medicine·Nassima Ait-DaoudDerek Blevins

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Citations

Jun 5, 2021·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yu SunJianhong Wei

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