Area under the plasma concentration-time curve of inorganic fluoride following sevoflurane anesthesia correlates with CYP2E1 mRNA level in mononuclear cells

Anesthesiology. 2000 Jun;92(6):1661-6. doi: 10.1097/00000542-200006000-00025.

Abstract

Background: Because the amount of inorganic fluoride released after anesthesia with sevoflurane depends on the dose of administered sevoflurane and cytochrome P450 (CYP) 2E1 activity in the liver, a reliable and noninvasive probe for CYP2E1 would be useful for predicting plasma inorganic fluoride levels after anesthesia. In this study, the authors evaluated the relation between plasma concentration of inorganic fluoride after sevoflurane anesthesia and CYP2E1 mRNA level in mononuclear cells.

Methods: Twenty patients (American Society of Anesthesiologists physical status I), aged 20-68 yr undergoing body surface surgery with general anesthesia with sevoflurane were enrolled. One milliliter of blood was obtained before administration of sevoflurane and mononuclear cells were obtained. Levels of CYP2E1 mRNA in mononuclear cells were measured by competitive reverse transcription polymerase chain reaction with a specific primer and competitor for CYP2E1 mRNA.

Results: There was a significant correlation between level of CYP2E1 mRNA in mononuclear cells and the area under the plasma concentration-time curve of plasma inorganic fluoride from the beginning of sevoflurane administration to infinity in uninduced and uninhibited patients (r2 = 0.56; P < 0.01).

Conclusions: Area under the plasma concentration-time curve of inorganic fluoride after sevoflurane anesthesia correlates with CYP2E1 mRNA in mononuclear cells in peripheral blood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anesthesia, Inhalation*
  • Anesthetics, Inhalation* / pharmacokinetics
  • Area Under Curve
  • Cytochrome P-450 CYP2E1 / biosynthesis*
  • Female
  • Fluorides / blood*
  • Humans
  • Leukocytes, Mononuclear / enzymology*
  • Male
  • Methyl Ethers* / pharmacokinetics
  • Middle Aged
  • RNA, Messenger / biosynthesis*
  • Regression Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sevoflurane

Substances

  • Anesthetics, Inhalation
  • Methyl Ethers
  • RNA, Messenger
  • Sevoflurane
  • Cytochrome P-450 CYP2E1
  • Fluorides