PiLeJe Laboratoire, 31-35 rue de la Fédération, 75015, Paris, France.
PiLeJe Industrie, Les Tiolans, 03800, Saint-Bonnet-de-Rochefort, France.
Drugs R D. 2024 Sep;24(3):415-423. doi: 10.1007/s40268-024-00482-6. Epub 2024 Aug 22.
Two main types of galenic formulation, immediate release and prolonged release, have been developed to optimize melatonin bioavailability. We recently described the kinetic profile of a prolonged-release form generating a peak of plasma melatonin 1 h (T) after intake, followed by a prolonged decay over time. We have developed a new oral form of melatonin with the aim of producing a melatonin peak several hours after intake.
The objective is to investigate melatonin bioavailability after administration of this new delayed-release form (DR form).
In this single-centre open-label study, 12 healthy male volunteers received one tablet of the DR form containing 1.9 mg melatonin, 10 mg zinc and 200 mg lemon balm extract (Melissa officinalis L aerial parts). Blood samples were collected for 12 h, beginning at 8:00 am. Plasma concentrations of melatonin and 6-sulfatoxymelatonin (6-SMT), the main hepatic melatonin metabolite, were determined by radioimmunoassay.
A progressive increase in plasma melatonin concentrations was observed from 20 min and a peak about 3 h after intake (C 740 ± 824 pg/mL; T 179 ± 60 min). Concentrations remained high between 140 and 220 min, the concentration remaining physiologically significant (over 100 pg/mL) up to 7 h after intake. The DR form was well tolerated.
The melatonin release profile was consistent with what was anticipated for the DR form. The DR form generated a 2 h delayed T compared with a prolonged-release form previously evaluated. This suggests that the DR form is suitable for the treatment of certain sleep disorders such as short sleep duration or early awakening.
Registration number: NCT05419466.
为了优化褪黑素的生物利用度，已经开发出两种主要的制剂类型，即速释制剂和缓控释制剂。我们最近描述了一种缓控释制剂的药代动力学特征，该制剂在摄入后 1 小时（T）达到血浆褪黑素峰值，随后随时间延长而逐渐下降。我们开发了一种新的褪黑素口服制剂，旨在使摄入后数小时达到褪黑素峰值。
研究该新的缓控释制剂（DR 制剂）给药后的褪黑素生物利用度。
在这项单中心、开放标签研究中，12 名健康男性志愿者服用 1 片 DR 制剂，该制剂含有 1.9 毫克褪黑素、10 毫克锌和 200 毫克柠檬香脂（ Melissa officinalis L.地上部分）提取物。从上午 8:00 开始，采集 12 小时的血样。采用放射免疫法测定血浆中褪黑素和主要的肝内褪黑素代谢产物 6-硫酸褪黑素（6-SMT）的浓度。
从 20 分钟开始，血浆褪黑素浓度逐渐升高，摄入后约 3 小时达到峰值（C 740 ± 824 pg/mL；T 179 ± 60 min）。在 140-220 分钟之间，浓度保持较高水平，在摄入后 7 小时内仍保持生理意义上的显著水平（超过 100 pg/mL）。DR 制剂耐受性良好。
褪黑素释放曲线与 DR 制剂的预期一致。与之前评估的缓控释制剂相比，DR 制剂的 T 延迟了 2 小时。这表明 DR 制剂适合治疗某些睡眠障碍，如睡眠时间短或早醒。
注册号：NCT05419466。
