PMID: 7793652Jun 1, 1995

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

Anesthesiology
E D KharaschM D Karol

Abstract

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

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Citations

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
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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

Related Concepts

Hexafluoroisopropanol
Ultane
1-Propanol
Anesthetic Effect
Cytochrome P-450 Oxygenase
Ethers
Fluorides
Methyl Ethers
Oxidoreductases, N-Demethylating
Cytochrome P-450 CYP2E1

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