Randomized, Double-Blind, Phase I Pharmacokinetic Study of Subcutaneous Recombinant Human Superoxide Dismutase (rhSOD) in Healthy Volunteers

Excessive reactive oxygen species production, including from microgravity-induced oxidative stress in astronauts, contributes to numerous disease processes, and exogenous superoxide dismutase (SOD) supplementation offers a potential therapeutic countermeasure. This randomized, double-blind, placebo-controlled Phase I study evaluated the safety, tolerability, and pharmacokinetics of subcutaneous recombinant human Cu/Zn-SOD (rhSOD) given every 12 hours to 16 healthy volunteers across single-dose and multiple-dose cohorts, with pharmacokinetic sampling analyzed to derive volume of distribution, clearance, and half-life at steady state. No serious adverse events occurred, injection site erythema (objectively measured via standardized photographic assessment) was comparable to placebo, and subcutaneous rhSOD produced a favorable, sustained plasma concentration-time profile compared with the rapid elimination seen after intravenous SOD administration. The favorable safety, tolerability, and pharmacokinetic profile supports further clinical development of subcutaneous rhSOD for conditions involving excessive oxidative stress or SOD deficiency, including potential applications in extended spaceflight.