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Background: 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 max ) 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., Objective: The objective is to investigate melatonin bioavailability after administration of this new delayed-release form (DR form)., Methods: 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., Results: A progressive increase in plasma melatonin concentrations was observed from 20 min and a peak about 3 h after intake (C max 740 ± 824 pg/mL; T max 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., Conclusions: The melatonin release profile was consistent with what was anticipated for the DR form. The DR form generated a 2 h delayed T max 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., Trial Registry: Registration number: NCT05419466., (© 2024. The Author(s).)

Background: The benefit of exogenous melatonin is based on its bioavailability, which depends on the galenic form, the route of administration, the dosage, and the individual absorption and rate of hepatic metabolism., Objective: The objective of this study is to investigate the bioavailability of melatonin after administration of an oral prolonged-release tablet (PR form) and an immediate-release sublingual spray (IR form). The main metabolite of melatonin, 6-sulfatoxymelatonin (6-SMT), was also measured, which has not been done in previous studies. Its determination is important as an index of the hepatic transformation of melatonin., Methods: In this single-center, open-label, randomized, crossover study, 14 healthy male volunteers received one tablet of the PR form (1.9 mg melatonin) or two sprays of the IR form (1 mg melatonin) during two visits separated by a washout period. Blood samples were collected over 7 and 9 h for the IR and PR form, respectively, to determine the main pharmacokinetic parameters., Results: The observed kinetics were consistent with those expected for immediate and prolonged-release forms. Pulverization of the spray resulted in an early, high plasma melatonin peak (C max : 2332 ± 950 pg/mL; T max : 23.3 ± 6.5 min), whereas tablet intake produced a lower peak (C max : 1151 ± 565 pg/mL; T max : 64.2 ± 44.2 min; p < 0.001 for comparison of C max and T max ) followed by a plasma melatonin plateau and a more prolonged decay over time. Plasma melatonin/6-SMT AUC 0-540/420 ratio was 0.09 for the PR form and 0.16 for the IR form. Both galenic forms were well tolerated., Conclusions: The results suggest that the galenic forms containing melatonin assessed in this study are suitable for the treatment of certain sleep disorders such as sleep onset delay and transient nocturnal awakenings for the IR form and insomnia for the PR form., Trial Registry: Registration number: NCT04574141., (© 2023. The Author(s).)