Detection of exhaled hydrogen sulphide gas in healthy human volunteers during intravenous administration of sodium sulphide.
BACKGROUND
Hydrogen sulphide (H(2)S) 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 H(2)S to the tissues. In the current study, we have measured H(2)S 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(2)S concentrations using a custom-made device based on a sulphide gas detector (Interscan).


RESULTS
Administration of IK-1001, a parenteral formulation of Na(2)S (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 H(2)S was observed to be higher than the ambient concentration of H(2)S gas in room air, indicative of on-going endogenous H(2)S production in human subjects. Upon intravenous administration of Na(2)S, a rapid elevation of exhaled H(2)S concentrations was observed. The amount of exhaled H(2)S rapidly decreased after discontinuation of the infusion of Na(2)S.


CONCLUSIONS
Exhaled H(2)S represents a detectable route of elimination after parenteral administration of Na(2)S.
Toombs
Christopher F
CF
Discovery Science, Ikaria, Seattle, WA 98102, USA.
Insko
Michael A
MA
Wintner
Edward A
EA
Deckwerth
Thomas L
TL
Usansky
Helen
H
Jamil
Khurram
K
Goldstein
Brahm
B
Cooreman
Michael
M
Szabo
Csaba
C
D001944:Breath Tests / Q000379:methods; D002852:Chromatography, Ion Exchange; D015331:Cohort Studies; D045853:Exhalation; D006801:Humans; D006862:Hydrogen Sulfide / Q000032:analysis*; D007262:Infusions, Intravenous; D012903:Smell; D013440:Sulfides / Q000008:administration & dosage* / Q000097:blood; D013885:Thiosulfates / Q000097:blood
D013440:Sulfides; D013885:Thiosulfates; C033479:sodium sulfide; D006862:Hydrogen Sulfide