A Randomized, Double-Blind, Crossover Study to Investigate the Pharmacokinetics of Extended-Release Melatonin Compared to Immediate-Release Melatonin in Healthy Adults.
Study Goal
The researchers aimed to compare the pharmacokinetics of extended-release melatonin (4 mg) versus immediate-release melatonin (4 mg) in healthy adults to assess its potential for sleep disorder treatment.
Results Summary
Extended-release melatonin showed a longer time to peak concentration and elimination half-life compared to immediate-release melatonin, sustaining elevated melatonin levels for 6 hours. No clinically relevant adverse events were observed, and safety parameters remained normal for both formulations.
Population
18 healthy adults, ages 18-65 years.
Effective Dosage
4 mg (single dose for each formulation).
Duration
Single administration with a 7-day washout period between crossover phases.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
Extended-release melatonin (4 mg) | increase | time to peak concentration | 18 healthy adults, ages 18-65 years | 1.56 vs 0.6 h | had a longer time to peak concentration | #1 |
Extended-release melatonin (4 mg) | increase | elimination half-life | 18 healthy adults, ages 18-65 years | 1.63 vs 0.95 h | had a longer elimination half-life | #2 |
Extended-release melatonin (4 mg) | decrease | maximum concentration | 18 healthy adults, ages 18-65 years | 7581 pg/mL vs 13120 pg/mL | had a lower maximum concentration | #3 |
Extended-release melatonin (4 mg) | increase | melatonin levels | 18 healthy adults, ages 18-65 years | in as little as 15 min | raised melatonin levels | #4 |
Extended-release melatonin (4 mg) | increase | melatonin levels | 18 healthy adults, ages 18-65 years | >300 pg/mL for 6 h | sustained elevated melatonin levels | #5 |
Extended-release melatonin (4 mg) | decrease | melatonin levels | 18 healthy adults, ages 18-65 years | 50 pg/mL by 9 h | melatonin levels falling below | #6 |
Extended-release melatonin (4 mg) | no change | adverse events | 18 healthy adults, ages 18-65 years | no clinically relevant adverse events | No clinically relevant adverse events were observed | #7 |
Extended-release melatonin (4 mg) | no change | safety parameters | 18 healthy adults, ages 18-65 years | within normal ranges | safety parameters remained within normal ranges | #8 |
Immediate-release melatonin (4 mg) | no change | adverse events | 18 healthy adults, ages 18-65 years | no clinically relevant adverse events | No clinically relevant adverse events were observed | #9 |
Immediate-release melatonin (4 mg) | no change | safety parameters | 18 healthy adults, ages 18-65 years | within normal ranges | safety parameters remained within normal ranges | #10 |
Exogenous melatonin can be helpful for treatment of some sleep disorders. However, immediate-release formulations are rapidly absorbed and cleared from the body making it difficult to provide coverage for an entire sleep period. Extended-release melatonin formulations can better mimic the naturally occurring melatonin profile and increase efficacy, but few studies have reported on their pharmacokinetics. To assess the pharmacokinetics of extended-release melatonin, we conducted a randomized, double-blind, crossover study of extended-release melatonin (4 mg) compared to immediate-release melatonin (4 mg) in 18 healthy adults, ages 18-65 years. Participants received immediate-release or extended-release melatonin in clinic after an 8 h fast, and blood samples were taken over a 10-h period. After a 7-day washout period, the same procedures were repeated with the melatonin form not previously received. Extended-release melatonin had a longer time to peak concentration (1.56 vs 0.6 h) and elimination half-life (1.63 vs 0.95 h) compared with immediate-release melatonin. Maximum concentration was lower for extended-release melatonin compared with immediate-release melatonin (7581 pg/mL vs 13120 pg/mL). Extended-release melatonin raised melatonin levels in as little as 15 min and sustained elevated melatonin levels (>300 pg/mL) for 6 h before falling below 50 pg/mL by 9 h. No clinically relevant adverse events were observed, and safety parameters remained within normal ranges for both formulations. The pharmacokinetic profile of this extended-release melatonin formulation suggests that it could be used for future efficacy studies of melatonin and sleep outcomes. This trial is registered at ClinicalTrials.gov, NCT04067791.