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

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.