Bioavailability of Oniria®, a Melatonin Prolonged-Release Formulation, Versus Immediate-Release Melatonin in Healthy Volunteers

Background Melatonin is an endogenous substance which plays a key role in sleep induction by reducing sleep onset latency; it has been approved by the European Food Safety Authority as a food supplement for exogenous administration. Oniria (R) is a food supplement formulated as 1.98 mg of prolonged-release melatonin tablets; it displays a dual dissolution profile in vitro. Objectives The main objective of the present study was to evaluate the relative oral bioavailability of Oniria (R), in comparison with immediate-release tablets (IRT) with a similar melatonin content as a reference. We also attempted to characterize the circadian rhythm of endogenous melatonin. Methods We performed an open-label, cross-over, randomized, phase I clinical study with two sequences and three periods involving 14 healthy volunteers. We characterized the endogenous melatonin circadian profile (period 1) and pharmacokinetics (PK) of both Oniria (R) and the reference melatonin (periods 2 and 3). Results Two phases were clearly differentiated in the PK profile of Oniria (R). An initial one, from dosing up to 2 h, and a delayed one from 2 to 11 h post-administration. During the initial phase, both melatonin formulations were equivalent, with a C-max value close to 4000 pg/mL. However, in the delayed phase, Oniria (R) showed significantly higher melatonin concentrations than the IRT (three times higher at 4-6 h post-administration). Moreover, Oniria (R) exhibited concentrations above the endogenous melatonin peak of 80 pg/mL for up to 2.5 h versus the reference formulation, potentially suggesting an effect of Oniria (R), not only in the induction of sleep, but also in the maintenance. Conclusion Oniria (R) could be a highly promising food supplement, not only for sleep induction but also for the maintenance of sleep.