Metabolism of Isoflurane in Patients Receiving Isoniazid

Gauntlett, Ian S.; Koblin, Donald D.; Fahey, Mark R.; Konopka, Krystyna; Gruenke, Larry D.; Waskell, Lucy; Eger, Edmond I.

doi:10.1097/00132586-199010000-00004

Cited by 9 publications

(4 citation statements)

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“…We assumed a 90.4% recovery of organic fluoride based on results from earlier studies (13). Nonvolatile organic fluoride from urine samples was calculated by subtracting the free fluoride ion in the original sample from the total fluoride content determined by the sodium fusion technique, after correction for the efficiency of organic fluoride detection.…”

Section: Fluoride Analysesmentioning

confidence: 99%

Fluoride Metabolites After Prolonged Exposure of Volunteers and Patients to Desflurane

Sutton

Koblin

Gruenke

et al. 1991

Anesthesia & Analgesia

106

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We examined the metabolism of desflurane in 13 healthy volunteers given 7.35 +/- 0.81 MAC-hours (mean +/- SD) of desflurane and 26 surgical patients given 3.08 +/- 1.84 MAC-hours (mean +/- SD). Markers of desflurane metabolism included fluoride ion measured via an ion-specific electrode, nonvolatile organic fluoride measured after sodium fusion of urine samples, and trifluoroacetic acid determined by a gas chromatographic-mass spectrometric method. In both volunteer and patient groups, postanesthesia serum fluoride ion concentrations did not differ from background fluoride ion concentrations. Similarly, postanesthesia urinary excretion of fluoride ion and organic fluoride in volunteers was comparable to preanesthesia excretion rates. However, small but significant levels of trifluoroacetic acid were found in both serum and urine from volunteers after exposure to desflurane. A peak serum concentration of 0.38 +/- 0.17 mumol/L of trifluoroacetic acid and a peak urinary excretion rate of 0.169 +/- 0.107 mumol/h were detected in volunteers at 24 h after desflurane exposure. Although these increases in trifluoroacetic acid after exposure to desflurane were statistically significant, they are approximately 10-fold less than levels seen after exposure to isoflurane. Thus, desflurane strongly resists biodegradation, but a small amount is metabolized in humans.

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Section: Fluoride Analysesmentioning

confidence: 99%

Fluoride Metabolites After Prolonged Exposure of Volunteers and Patients to Desflurane

Sutton

Koblin

Gruenke

et al. 1991

Anesthesia & Analgesia

106

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“…In this study, TFA was tested at concentrations ranging from 0.0001 to 1 mM. Another study has been conducted demonstrating serum concentrations of TFA with known MAC hours of isoflurane, indicating that under these conditions (patients treated with isoniazid resulting in enzyme induction) the TFA concentrations are greater than 0.01 mM (15). Furthermore, the peak concentration of excreted TFA found in human urine was 1-1.3 mM (14), when patients were exposed to isoflurane at a concentration of 0.9%.…”

Section: Resultsmentioning

confidence: 99%

Trifluoroacetic Acid Activates ATP-Sensitive K+ Channels in Rabbit Ventricular Myocytes

Han

Kim

2001

Biochemical and Biophysical Research Communications

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“…Post-surgical blood TFA levels were monitored by Gauntlett et al (1989) in two patients pretreated with the enzyme-inducing agent isoniazid and then anesthetized with isoflurane. TFA concentrations as high as 40 μM were observed two days after surgery and remained elevated for at least a week.…”

Section: Discussionmentioning

confidence: 99%

Trifluoroacetate is an allosteric modulator with selective actions at the glycine receptor

2012

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Trifluoroacetic acid is a metabolite of the inhaled anesthetics halothane, desflurane and isoflurane as well as a major contaminant in HPLC-purified peptides. Ligand-gated ion channels, including cys-loop receptors such as the glycine receptor, have been the targets of peptide-based drug design and are considered to be likely candidates for mediating the effects of anesthetics in vivo, but the possible secondary contributions of contaminants and metabolites to these effects have not been studied. We used two-electrode voltage-clamp electrophysiology to test glycine, GABAA and 5-HT3 receptors expressed in Xenopus oocytes for their sensitivities to sodium trifluoroacetate. Trifluoroacetate (100 μM–3 mM) enhanced the currents elicited by low concentrations of glycine applied to α1 homomeric and α1β heteromeric glycine receptors, but it had no effects when co-applied with a maximally-effective glycine concentration. Trifluoroacetate had no effects on α1β2γ2S GABAA or 5-HT3A receptors at any GABA or serotonin concentration tested. The results demonstrate that trifluoroacetate acts as an allosteric modulator at the glycine receptor with greater specificity than other known modulators. These results have important implications for both the secondary effects of volatile anesthetics and the presence of contaminating trifluoroacetate in HPLC-purified peptides, which is potentially an important source of experimental variability or error that requires control.

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Metabolism of Isoflurane in Patients Receiving Isoniazid

Cited by 9 publications

References 0 publications

Fluoride Metabolites After Prolonged Exposure of Volunteers and Patients to Desflurane

Fluoride Metabolites After Prolonged Exposure of Volunteers and Patients to Desflurane

Trifluoroacetic Acid Activates ATP-Sensitive K+ Channels in Rabbit Ventricular Myocytes

Trifluoroacetate is an allosteric modulator with selective actions at the glycine receptor

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