γ-Hydroxybutyric Acid-Ethanol Drug-Drug Interaction: Reversal of Toxicity with Monocarboxylate Transporter 1 Inhibitors.

The Journal of Pharmacology and Experimental Therapeutics
Vivian Rodriguez-Cruz, Marilyn E Morris

Abstract

The drug of abuse, γ-hydroxybutyric acid (GHB), is commonly co-ingested with ethanol, resulting in a high incidence of toxicity and death. Our laboratory has previously reported that GHB is a substrate for the monocarboxylate transporters (MCTs), necessary for its absorption, renal clearance, and tissue distribution, including across the blood-brain barrier. Our goal was to investigate the drug-drug interaction (DDI) between GHB and ethanol and to evaluate MCT1 inhibition as a strategy to reverse toxicity. The toxicokinetics of this DDI were investigated, including brain-to-plasma concentration ratios, in the presence and absence of ethanol. The toxicodynamic parameters examined were respiratory depression (breathing frequency, tidal volume) and sedation (time of return-of-righting reflex). Ethanol was administered (2 g/kg i.v.) 5 minutes before the intravenous or oral administration of GHB, and MCT1 inhibitors AZD-3965 and AR-C155858 (5 mg/kg i.v.) were administered 60 minutes after GHB administration. Ethanol administration did not alter the toxicokinetics or respiratory depression caused by GHB after intravenous or oral administration; however, it significantly increased the sedation effect, measured by return-to-righting ti...Continue Reading

References

Feb 22, 2005·The Journal of Pharmacology and Experimental Therapeutics·Marilyn E MorrisQi Wang
May 19, 2006·The Journal of Pharmacology and Experimental Therapeutics·Qi WangMarilyn E Morris
Sep 16, 2006·Journal of Clinical Psychopharmacology·Dung ThaiChristine A Haller
Jul 7, 2007·The American Journal of Drug and Alcohol Abuse·Susan Y KimPaul D Blanc
Aug 23, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Qi WangMarilyn E Morris
Feb 24, 2010·Computer Methods and Programs in Biomedicine·Yong ZhangShaofei Xie
Mar 11, 2010·The Journal of Pharmacology and Experimental Therapeutics·Melanie A FelmleeMarilyn E Morris
Sep 10, 2010·The American Journal of Emergency Medicine·Deborah L ZvosecJo Ellen Dyer
Oct 25, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Samuel A RoikoMarilyn E Morris
Nov 10, 2012·Transplant International : Official Journal of the European Society for Organ Transplantation·Clara PåhlmanHenrik Ekberg
Feb 9, 2013·The Journal of Pharmacology and Experimental Therapeutics·Bridget L Morse, Marilyn E Morris
Feb 21, 2013·Experimental and Clinical Psychopharmacology·Matthew W Johnson, Roland R Griffiths
Mar 20, 2013·Molecular Aspects of Medicine·Andrew P Halestrap
Jun 25, 2013·Current Pharmaceutical Design·Nisha Vijay, Marilyn E Morris
Jul 3, 2013·The Journal of Pharmacology and Experimental Therapeutics·Bridget L Morse, Marilyn E Morris
Sep 2, 2016·Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine·Evangelia LiakoniMatthias E Liechti
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Apr 24, 2019·The Journal of Pharmacology and Experimental Therapeutics·Kristin E Follman, Marilyn E Morris

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