Clinical Pharmacology Department, Hospital Universitario de La Princesa Instituto de Investigación Sanitaria La Princesa (IP), Universidad Autónoma de Madrid (UAM), C/ Diego de León, 62, 28006, Madrid, Spain.
Plataforma SCReN (Spanish Clinical Research Network), Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain.
Drugs R D. 2022 Sep;22(3):235-243. doi: 10.1007/s40268-022-00394-3. Epub 2022 Aug 2.
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.
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.
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).
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 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.
Oniria could be a highly promising food supplement, not only for sleep induction but also for the maintenance of sleep.
褪黑素是一种内源性物质，通过减少睡眠潜伏期来发挥诱导睡眠的关键作用；它已被欧洲食品安全局批准作为外源性给药的食品补充剂。Oniria 是一种褪黑素延时释放片的食品补充剂，具有双重体外溶出特性。
本研究的主要目的是评估 Oniria 的相对口服生物利用度，与具有相似褪黑素含量的即时释放片（IRT）作为参比制剂进行比较。我们还试图描述内源性褪黑素的昼夜节律。
我们进行了一项开放标签、交叉、随机、I 期临床试验，有两个序列和三个周期，涉及 14 名健康志愿者。我们描述了内源性褪黑素昼夜节律特征（第 1 周期）和 Oniria 及参比褪黑素的药代动力学（第 2 和第 3 周期）。
Oniria 的 PK 特征明显分为两个阶段。初始阶段从给药到 2 小时，延迟阶段从 2 小时到 11 小时给药后。在初始阶段，两种褪黑素制剂是等效的，C 值接近 4000pg/mL。然而，在延迟阶段，Oniria 显示出比 IRT 更高的褪黑素浓度（给药后 4-6 小时高三倍）。此外，Oniria 表现出的浓度高于内源性褪黑素峰值 80pg/mL 长达 2.5 小时，与参比制剂相比，可能表明 Oniria 不仅具有诱导睡眠的作用，还有维持睡眠的作用。
Oniria 可能是一种很有前途的食品补充剂，不仅可用于诱导睡眠，还可用于维持睡眠。
