Randomized, Open-Label Pharmacokinetic Study of Oral Magnesium Oxide in Healthy Volunteers

Background 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, dose-dependent absorption, and pharmacokinetics of oral magnesium oxide at two dosage levels in healthy male volunteers. Methods 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. Plasma magnesium concentrations were measured at baseline and multiple time points up to 12 hours post-dose using colorimetric assay. Pharmacokinetic parameters including Cmax, Tmax, AUC, half-life, mean residence time, and clearance were calculated using non-compartmental analysis. Safety was assessed by monitoring vital signs, laboratory parameters, ECG, and adverse events. Results The study showed saturable, nonlinear absorption kinetics with no proportional increase in Cmax or AUC at the higher dose. Incremental exposure parameters were also comparable between doses, further reinforcing the presence of saturable and nonlinear absorption kinetics. 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. Conclusion: In summary, this study demonstrates that oral MgO displays rate differences without proportional exposure gains across 750–2000 mg, supporting a saturable absorption model with a practical ceiling on systemic delivery. These findings provide a pharmacokinetic rationale for cautious dose escalation and support the feasibility of MgO as a well-tolerated oral option for perioperative magnesium optimization.