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(®) 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(®), 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(®) and the reference melatonin (periods 2 and 3). RESULTS: Two phases were clearly differentiated in the PK profile of Oniria(®). 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(®) showed significantly higher melatonin concentrations than the IRT (three times higher at 4–6 h post-administration). Moreover, Oniria(®) 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(®), not only in the induction of sleep, but also in the maintenance. CONCLUSION: Oniria(®) could be a highly promising food supplement, not only for sleep induction but also for the maintenance of sleep.