Discovery Science, Ikaria, Seattle, WA 98102, USA.
Br J Clin Pharmacol. 2010 Jun;69(6):626-36. doi: 10.1111/j.1365-2125.2010.03636.x.
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.
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).
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.
Exhaled H(2)S represents a detectable route of elimination after parenteral administration of Na(2)S.
硫化氢（H(2)S）是一种内源性气体信号分子，也是一种有潜力的治疗药物。新出现的研究表明，它在多种心血管疾病和危重病中具有治疗潜力。静脉给予硫氢化钠可增加内源性硫氢化物浓度，从而将 H(2)S 输送到组织中。在当前的研究中，我们在一项人体 I 期安全性和耐受性研究中，测量了健康志愿者在接受递增剂量的硫氢化钠后呼气中的 H(2)S 浓度。
我们通过硫氢化钠与单溴双马来酰亚胺在血液中的体外衍生化反应来测量血液中的反应性硫，形成硫代双马来酰亚胺，通过离子色谱法测量血中硫代硫酸盐（硫代硫酸盐的主要氧化代谢物）的浓度。我们使用一种基于硫化物气体探测器（Interscan）的定制设备测量呼气中的 H(2)S 浓度。
静脉注射 IK-1001（Na(2)S 的一种注射用制剂，0.005-0.20 mg kg(-1)，静脉输注 1 分钟）可诱导血液中硫氢化物和硫代硫酸盐浓度升高，高于基线水平，在 0.10 mg kg(-1)剂量及更高剂量的 IK-1001 给药后 1-5 分钟内即可观察到。在所有受试者中，基础呼气中的 H(2)S 被观察到高于室内空气中 H(2)S 气体的环境浓度，表明人体中存在持续的内源性 H(2)S 产生。静脉注射 Na(2)S 后，呼气中的 H(2)S 浓度迅速升高。停止 Na(2)S 输注后，呼出的 H(2)S 量迅速减少。
静脉给予 Na(2)S 后，呼气中的 H(2)S 是一种可检测的消除途径。
