Systemic molecular hydrogen exposure is governed by pulmonary clearance: insights from an arterioarterial shunt approach

This study establishes a quantitative framework for hydrogen (H 2 ) pharmacokinetics, demonstrating that inhalation is the only way to achieve rapid and homogeneous systemic exposure, whereas hydrogen-rich water delivers H 2 only to downstream organs. Using complementary physiological, intragastric, and high-dose systemic approaches, we validate a nonsaturable pulmonary clearance model across clinically relevant and supraphysiological concentrations. These findings resolve inconsistencies in the literature and redefine how hydrogen-based therapies should be interpreted and optimized.