Detection of exhaled hydrogen sulphide gas in healthy human volunteers during intravenous administration of sodium sulphide

Christopher F. Toombs, Michael A. Insko, Edward A. Wintner, Thomas L. Deckwerth, Helen Usansky, Khurram Jamil, Brahm Goldstein, Michael Cooreman, Csaba Szabo

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    Abstract

    INTRODUCTION Hydrogen sulphide (H2S) is an endogenous gaseous signaling molecule and potential therapeutic agent. Emerging studies indicate its therapeutic potential in a variety of cardiovascular diseases and in critical illness. Augmentation of endogenous sulphide concentrations by intravenous administration of sodium sulphide can be used for the delivery of H2S to the tissues. In the current study, we have measured H 2S concentrations in the exhaled breath of healthy human volunteers subjected to increasing doses sodium sulphide in a human phase I safety and tolerability study. METHODS We have measured reactive sulphide in the blood via ex vivo derivatization of sulphide with monobromobimane to form sulphide-dibimane and blood concentrations of thiosulfate (major oxidative metabolite of sulphide) via ion chromatography. We have measured exhaled H 2S concentrations using a custom-made device based on a sulphide gas detector (Interscan). RESULTS Administration of IK-1001, a parenteral formulation of Na2S (0.005-0.20 mg kg-1, i.v., infused over 1 min) induced an elevation of blood sulphide and thiosulfate concentrations over baseline, which was observed within the first 1-5 min following administration of IK-1001 at 0.10 mg kg-1 dose and higher. In all subjects, basal exhaled H2S was observed to be higher than the ambient concentration of H2S gas in room air, indicative of on-going endogenous H2S production in human subjects. Upon intravenous administration of Na2S, a rapid elevation of exhaled H2S concentrations was observed. The amount of exhaled H2S rapidly decreased after discontinuation of the infusion of Na2S. CONCLUSION Exhaled H2S represents a detectable route of elimination after parenteral administration of Na2S.

    Original languageEnglish (US)
    Pages (from-to)626-636
    Number of pages11
    JournalBritish Journal of Clinical Pharmacology
    Volume69
    Issue number6
    DOIs
    StatePublished - Jun 1 2010

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    Keywords

    • Cardiovascular
    • Excretion
    • Hydrogen sulphide
    • Lung
    • Metabolism
    • Pulmonary

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmacology (medical)

    Cite this

    Toombs, C. F., Insko, M. A., Wintner, E. A., Deckwerth, T. L., Usansky, H., Jamil, K., Goldstein, B., Cooreman, M., & Szabo, C. (2010). Detection of exhaled hydrogen sulphide gas in healthy human volunteers during intravenous administration of sodium sulphide. British Journal of Clinical Pharmacology, 69(6), 626-636. https://doi.org/10.1111/j.1365-2125.2010.03636.x