PMID: 7793652Jun 1, 1995

Clinical sevoflurane metabolism and disposition. II. The role of cytochrome P450 2E1 in fluoride and hexafluoroisopropanol formation

E D KharaschM D Karol


Sevoflurane is metabolized to free fluoride and hexafluoroisopropanol (HFIP). Cytochrome P450 2E1 is the major isoform responsible for sevoflurane metabolism by human liver microsomes in vitro. This investigation tested the hypothesis that P450 2E1 is predominantly responsible for sevoflurane metabolism in vivo. Disulfiram, which is converted in vivo to a selective inhibitor of P450 2E1, was used as a metabolic probe for P450 2E1. Twenty-one patients within 30% of ideal body weight, who provided institutional review board-approved informed consent and were randomized to receive disulfiram (500 mg oral, n = 11) or nothing (control, n = 10) the night before surgery, were evaluated. All patients received sevoflurane (2.7% end-tidal, 1.3 MAC) in oxygen for 3 h after propofol induction. Thereafter, sevoflurane was discontinued, and anesthesia was maintained with propofol, fentanyl, and nitrous oxide. Blood sevoflurane concentrations during anesthesia and for 8 h thereafter were measured by gas chromatography. Plasma and urine fluoride and total (unconjugated plus glucuronidated) HFIP concentrations were measured by an ion-selective electrode and by gas chromatography, respectively, during anesthesia and for 96 h postoperatively. Pat...Continue Reading


Nov 1, 1975·Anesthesia and Analgesia·R F WallinI J Stern
Jan 1, 1992·Critical Reviews in Toxicology·S A Wrighton, J C Stevens
Mar 1, 1991·Chemical Research in Toxicology·F P GuengerichM Iwasaki
Feb 11, 1992·Anesthesia and Analgesia·E J FrinkB R Brown
Nov 1, 1990·Chemical Research in Toxicology·R PeterC S Yang
Sep 1, 1990·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·D R Koop, D J Tierney
Dec 1, 1989·European Journal of Clinical Investigation·N PerrotP H Beaune
Mar 1, 1988·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·M S SchellerB L Partridge
Aug 1, 1994·British Journal of Anaesthesia·H HiguchiM Kanno
Apr 1, 1994·Clinical Pharmacology and Therapeutics·E D KharaschS Bosse
Jun 1, 1993·Clinical Pharmacology and Therapeutics·E D KharaschJ H Lillibridge


Sep 23, 2003·Anesthesia and Analgesia·G SummerW Schobersberger
Mar 24, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ying-Cheng HuangChung-Shan Yu
Apr 9, 2009·Expert Opinion on Pharmacotherapy·Fabrice Michel, Jean-Michel Constantin
Aug 20, 2020·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Rakesh V SondekoppamTimur J-P Özelsel
Aug 8, 1998·Clinical Pharmacology and Therapeutics·E D KharaschK E Thummel
Dec 1, 1995·Anesthesia and Analgesia·J G Kenna, R M Jones
Jul 24, 2004·Anesthesia and Analgesia·Alexander ReichHugo Van Aken
May 29, 2014·American Journal of Veterinary Research·Trevor T ZachariahMaureen A McMichael
Jul 1, 2016·Nursing Research·Edwin N Aroke, Jennifer R Dungan
Jul 15, 2020·Human & Experimental Toxicology·A M EmaraR M Elgarabawy
May 9, 2002·Drug Metabolism Reviews·Slobodan Rendic
Mar 17, 1999·Anesthesiology·E D KharaschK Cox
Jan 28, 2010·Transplant International : Official Journal of the European Society for Organ Transplantation·Justin S KoJae W Joh
Sep 18, 2015·F1000Research·Stefan De Hert, Anneliese Moerman
Jan 1, 2000·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·V HaufroidD Lison
Dec 1, 1995·Anesthesia and Analgesia·E D Kharasch
Jan 25, 2006·Anaesthesia·B P Sweeney, J Bromilow

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