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

Abstract

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. MethodsWe 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.

Features of using prolonged-release melatonin in patients with type 2 diabetes

“…Загалом у формі з пролонгованим вивільненням відбувається затримка пікової дози, процес триває від 90 до 210 хв, залежно від типу лікарської форми. Період напіввиведення також може подовжуватися, досягаючи від 3,5 до 4 годин [27]. Таким чином, лікарські форми мелатоніну з пролонгованим вивільненням забезпечують повільніше та триваліше всмоктування, ніж форми з негайним вивільненням.…”

Bioavailability of Melatonin after Administration of an Oral Prolonged-Release Tablet and an Immediate-Release Sublingual Spray in Healthy Male Volunteers

“…The prolonged-release tablet was developed to mimic the plateau observed with endogenous melatonin secretion, whereas the sublingual spray was designed to provide an early melatonin peak, and to limit first-pass hepatic metabolism, since vascularization is highly developed under the tongue. We also measured the metabolite 6-SMT, which has not been measured in previously published studies with such melatonin formulations [ 1 , 18 , 19 ]. Its determination is important as an index of the hepatic transformation of melatonin.…”