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

Research output: Contribution to journalArticle

67 Citations (Scopus)

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 2010
Externally publishedYes

Fingerprint

Hydrogen Sulfide
Sulfides
Intravenous Administration
Healthy Volunteers
Gases
Thiosulfates
sodium sulfide
Critical Illness
Chromatography
Cardiovascular Diseases
Air
Ions
Safety
Equipment and Supplies
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Detection of exhaled hydrogen sulphide gas in healthy human volunteers during intravenous administration of sodium sulphide. / Toombs, Christopher F.; Insko, Michael A.; Wintner, Edward A.; Deckwerth, Thomas L.; Usansky, Helen; Jamil, Khurram; Goldstein, Brahm; Cooreman, Michael; Szabo, Csaba.

In: British Journal of Clinical Pharmacology, Vol. 69, No. 6, 06.2010, p. 626-636.

Research output: Contribution to journalArticle

Toombs, Christopher F. ; Insko, Michael A. ; Wintner, Edward A. ; Deckwerth, Thomas L. ; Usansky, Helen ; Jamil, Khurram ; Goldstein, Brahm ; Cooreman, Michael ; Szabo, Csaba. / Detection of exhaled hydrogen sulphide gas in healthy human volunteers during intravenous administration of sodium sulphide. In: British Journal of Clinical Pharmacology. 2010 ; Vol. 69, No. 6. pp. 626-636.
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T1 - Detection of exhaled hydrogen sulphide gas in healthy human volunteers during intravenous administration of sodium sulphide

AU - Toombs, Christopher F.

AU - Insko, Michael A.

AU - Wintner, Edward A.

AU - Deckwerth, Thomas L.

AU - Usansky, Helen

AU - Jamil, Khurram

AU - Goldstein, Brahm

AU - Cooreman, Michael

AU - Szabo, Csaba

PY - 2010/6

Y1 - 2010/6

N2 - 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.

AB - 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.

KW - Cardiovascular

KW - Excretion

KW - Hydrogen sulphide

KW - Lung

KW - Metabolism

KW - Pulmonary

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