Randomized, open-label study of the short-term pharmacokinetics of oral magnesium oxide in healthy volunteers

Magnesium oxide, though poorly soluble with low bioavailability, is widely used for magnesium supplementation due to its high elemental content and affordability. This study aimed to evaluate the safety and short-term, absorption-related pharmacokinetics of oral magnesium oxide at two dosage levels in healthy male volunteers. A randomized, open-label pharmacokinetic study was conducted in 24 healthy male volunteers aged 18-45 years, who were equally assigned to receive a single oral dose of either 750 mg or 2000 mg of magnesium oxide. Serum magnesium concentrations were measured at baseline and multiple time points up to 12 h post-dose using a colorimetric assay. Pharmacokinetic parameters related to systemic exposure and absorption, including Cmax, Tmax, and AUC0-12, were calculated using non-compartmental analysis. Parameters dependent on terminal elimination (t1/2, AUC0-∞, CL/F, MRT) were not estimated because a clear terminal log-linear phase was not identifiable within the 12-hour sampling window. Safety was assessed by monitoring vital signs, laboratory parameters, ECG, and adverse events. The study showed non-dose-proportional systemic exposure, with no proportional increase in Cmax or AUC at the higher dose. Incremental exposure parameters were also comparable between doses, further suggesting non-dose-proportional absorption within the studied dose range. Tmax was significantly shorter in the 2000 mg group (p = 0.025). Both doses were well tolerated without serious adverse events or gastrointestinal side effects. In summary, this study characterizes the short-term absorption pharmacokinetics of oral magnesium oxide, demonstrating non-proportional systemic exposure across the 750-2000 mg dose range within the 12-hour observation period. As only two dose levels were evaluated, further studies with multiple doses and formal dose-proportionality analyses are required to clarify the underlying mechanisms. These findings provide exploratory pharmacokinetic insights and should not be extrapolated to clinical efficacy or perioperative dosing.