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.

中文翻译：

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Oniria® 的生物利用度，一种褪黑激素延长释放配方，与健康志愿者中的即时释放褪黑激素相比

背景

褪黑激素是一种内源性物质，通过减少入睡潜伏期在睡眠诱导中起关键作用；它已被欧洲食品安全局批准作为外源性管理的食品补充剂。Oniria ^®是一种食品补充剂，配方为 1.98 毫克褪黑激素缓释片；它在体外显示出双重溶出曲线。

目标

本研究的主要目的是评估 Oniria ^®的相对口服生物利用度，并与褪黑激素含量相似的速释片 (IRT) 作为参考进行比较。我们还试图描述内源性褪黑激素的昼夜节律。

方法

我们进行了一项开放标签、交叉、随机、I 期临床研究，包括两个序列和三个阶段，涉及 14 名健康志愿者。^{我们对 Oniria ®}和参考褪黑激素（第 2 和第 3 阶段）的内源性褪黑激素昼夜节律特征（第 1 阶段）和药代动力学 (PK) 进行了表征。

结果

^{Oniria ®}的 PK 曲线明显区分了两个阶段。初始一次，从给药到 2 小时，延迟一次，从给药后 2 到 11 小时。在初始阶段，两种褪黑激素制剂是等效的，C _max值接近 4000 pg/mL。然而，在延迟期，Oniria ^®的褪黑激素浓度显着高于 IRT（给药后 4-6 小时高出三倍）。此外，与参考配方相比，Oniria ^®的浓度高于 80 pg/mL 的内源性褪黑激素峰值长达 2.5 小时，这可能表明 Oniria ^®的作用不仅在于诱导睡眠，还在于维持睡眠。

结论

Oniria ^®可能是一种非常有前途的食品补充剂，不仅可以用于睡眠诱导，还可以用于维持睡眠。