Inhibition of CYP2E1 With Propylene Glycol Does Not Protect Against Hepatocellular Injury in Human Acetaminophen Daily-Dosing Model

Journal of Clinical Pharmacology
Michael GanetskySteven Salhanick

Abstract

Acetaminophen (APAP)-induced liver injury is initiated by metabolism of APAP by the cytochrome P-450 (CYP) system, primarily CYP2E1. We previously demonstrated CYP inhibition following administration of a liquid APAP formulation containing propylene glycol, a CYP2E1 inhibitor, and other excipients. This study was undertaken to determine if propylene glycol specifically inhibits production of CYP-derived metabolites and if propylene glycol reduces the rise in alanine aminotransferase (ALT) seen following prolonged APAP dosing. Human subjects were randomized to receive 4 g of APAP daily in one arm of the study or 4 g of APAP with 5 mL of 99% propylene glycol in the other arm, both for 14 days. After a washout period of at least 14 days, subjects were crossed over between arms. Outcomes were rise of ALT greater than 2 times baseline (responders) and proportion of randomly sampled CYP-derived metabolites relative to total metabolites produced. There was no difference in percentage of responders between treatment groups: 6 of 21 in the APAP group (29%) compared with 8 of 20 in the APAP + propylene glycol group (40%); chi-square, P = .59. For all subjects, the mean percentage of CYP-derived metabolites produced was 5.8% (APAP) versus...Continue Reading

References

Jun 1, 1989·Archives of Biochemistry and Biophysics·J L RaucyM Black
Mar 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·D C DahlinS D Nelson
Apr 22, 1993·Biochemical Pharmacology·K E ThummelJ T Slattery
Sep 25, 2004·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Mark W RussoPaul Watkins
Dec 1, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Anne M LarsonUNKNOWN Acute Liver Failure Study Group
Jul 6, 2006·JAMA : the Journal of the American Medical Association·Paul B WatkinsStephen C Harris
Jul 19, 2008·The New England Journal of Medicine·Kennon J Heard
Feb 26, 2010·Clinical Pharmacology and Therapeutics·J H WinnikeP B Watkins
Oct 22, 2010·Canadian Journal of Physiology and Pharmacology·Tomislav KelavaFilip Culo
Mar 5, 2011·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Mohammed A AlhelailKennon J Heard
Feb 26, 2013·Journal of Clinical Pharmacology·Michael GanetskySteven D Salhanick
May 10, 2013·Critical Reviews in Toxicology·Jeff R FowlesLynn H Pottenger
Dec 1, 2017·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·David D GumminWilliam Banner
Feb 6, 2018·Current Opinion in Toxicology·Anup Ramachandran, Hartmut Jaeschke

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Citations

Dec 11, 2019·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Michael GanetskySteven D Salhanick
Nov 18, 2021·Toxicology Letters·Ali Mohammad Pourbagher-ShahriOmid Mehrpour

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