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Detection of exhaled hydrogen sulphide gas in healthy human volunteers during intravenous administration of sodium sulphide
Author(s) -
Toombs Christopher F.,
Insko Michael A.,
Wintner Edward A.,
Deckwerth Thomas L.,
Usansky Helen,
Jamil Khurram,
Goldstein Brahm,
Cooreman Michael,
Szabo Csaba
Publication year - 2010
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2010.03636.x
Subject(s) - sodium thiosulfate , chemistry , hydrogen sulphide , pharmacokinetics , pharmacology , metabolite , derivatization , chromatography , biochemistry , medicine , organic chemistry , high performance liquid chromatography , sulfur
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Hydrogen sulphide (H 2 S) is a biological mediator and a potential therapeutic agent. In animal studies, the metabolism and pharmacokinetics of H 2 S have been characterized. WHAT THIS STUDY ADDS • This study is first to demonstrate the pharmacokinetics of an intravenously administered H 2 S formulation in humans, and to characterize the exhaled H 2 S response in humans. INTRODUCTION 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. CONCLUSION Exhaled H 2 S represents a detectable route of elimination after parenteral administration of Na 2 S.