Formulation-dependent differences in systemic glutathione availability: Comparative pharmacokinetics of orally dissolving film and tablet formulations in healthy adults

Background: Glutathione is a tripeptide involved in antioxidant defense; however, its systemic availability following oral administration remains controversial, and pharmacokinetic differences between formulations in humans are not well characterized. Objective: This study compared the pharmacokinetics and short-term supplementation effects of an orally dissolving film (ODF) and a conventional tablet formulation of glutathione in healthy adults. Methods: In Study I, a randomized open-label crossover trial evaluated single-dose (300 mg) pharmacokinetics following administration of ODF or tablets. In Study II, participants consumed ODF (100 mg/day) or tablets (100 mg/day) for 4 weeks. Results: Plasma glutathione concentrations were higher in the ODF group, with significant differences at 4 and 6 h. The ODF formulation showed a longer T_max and tended toward higher C_max and systemic exposure (iAUC_0–6h). During 4-week supplementation, both formulations increased circulating glutathione levels, with no significant changes in oxidative stress–related biomarkers. No adverse events were reported. Conclusions: The ODF formulation exhibited a distinct pharmacokinetic profile and showed a trend toward greater systemic glutathione exposure compared with the tablet formulation. These findings suggest that formulation characteristics may contribute to differences in the bioavailability and pharmacokinetic behavior of orally administered glutathione.Clinical trial registration: Clinical Research Information Service (CRIS), KCT0011710.